UBC Theses and Dissertations

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UBC Theses and Dissertations

Temporal patterning of electroshock and retrograde amnesia Jamieson, John Leslie 1972

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TEMPORAL PATTERNING OF ELECTROSHOCK AND RETROGRADE AMNESIA by JOHN LESLIE JAMIESON B.A.  U n i v e r s i t y of B r i t i s h Columbia, 1965  A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY i n the Department of Psychology  We accept t h i s t h e s i s as conforming to the r e q u i r e d standard  THE UNIVERSITY OF BRITISH COLUMBIA y  August, 1972  In presenting t h i s t h e s i s in p a r t i a l  f u l f i l m e n t o f the  requirements f o r  an advanced degree at the U n i v e r s i t y of B r i t i s h Columbia, I agree the L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r reference and I f u r t h e r agree that permission f o r s c h o l a r l y purposes may by h i s r e p r e s e n t a t i v e s .  study.  for e x t e n s i v e copying of t h i s t h e s i s  be granted by the Head of my It i s understood that  of t h i s t h e s i s f o r f i n a n c i a l gain written  that  permission.  Department of The U n i v e r s i t y of B r i t i s h Columbia Vancouver 8, Canada  s h a l l not  Department or  copying or  publication  be allowed without  my  ii  ABSTRACT  T r e a t m e n t s s u c h as e l e c t r o c o n v u l s i v e s h o c k (ECS) i m p a i r performance of l e a r n e d responses i f p r e s e n t e d s h o r t l y a f t e r but not i f delayed f o r a s u f f i c i e n t  time.  later  learning,  These g r a d i e n t s a r e f r e -  q u e n t l y termed r e t r o g r a d e a m n e s i a and i n t e r p r e t e d as r e f l e c t i n g a memory c o n s o l i d a t i o n p r o c e s s .  The p r e s e n t i n v e s t i g a t i o n was c o n c e r n e d  w i t h the r e l a t i o n s h i p of the l e n g t h of t h e g r a d i e n t produced by a s i n g l e ECS t o t h e d u r a t i o n o f t h e memory c o n s o l i d a t i o n p r o c e s s . In the f i r s t  e x p e r i m e n t , r a t s were t r a i n e d on a o n e - t r i a l  passive  a v o i d a n c e t a s k and t h e n p r e s e n t e d w i t h one o f t h r e e ECS t r e a t m e n t s . The t r e a t m e n t s w e r e f i v e ECSs o f 0.5 s e c o n d s d u r a t i o n s p a c e d  either  1 m i n u t e a p a r t , 5 s e c o n d s a p a r t , o r i n one c o n t i n u o u s 2.5 s e c o n d d u r ation burst.  The f i v e ECSs s p a c e d 1 m i n u t e a p a r t w e r e f o u n d t o i m -  p a i r p e r f o r m a n c e when p r e s e n t e d i m m e d i a t e l y , 1 h o u r , 24 h o u r s , and 48 h o u r s b u t n o t 9 d a y s a f t e r p a s s i v e a v o i d a n c e t r a i n i n g .  F i v e ECSs  s p a c e d 5 s e c o n d s a p a r t i m p a i r e d p e r f o r m a n c e when p r e s e n t e d i m m e d i a t e l y or 1 hour b u t n o t 24 h o u r s a f t e r  training.  I n contrast, the s i n g l e  2.5 s e c o n d d u r a t i o n ECS i m p a i r e d p e r f o r m a n c e when p r e s e n t e d immedia t e l y b u t n o t 1 hour o r l o n g e r a f t e r  training.  The i m p a i r m e n t s p r o -  duced by t h e f i v e ECSs s p a c e d 1 m i n u t e a p a r t a t 1 hour and 24 h o u r s were f o u n d t o be permanent o v e r 11 d a y s . The s e c o n d e x p e r i m e n t examined w h e t h e r  the long gradient pro-  duced by f i v e ECSs s p a c e d 1 m i n u t e a p a r t was q u a l i t a t i v e l y  different  f r o m s i n g l e ECS g r a d i e n t s . sented  F i v e ECSs s p a c e d 1 m i n u t e a p a r t w e r e  f o l l o w i n g passive avoidance t r a i n i n g  e t h e r or sodium p e n t o b a r b i t a l . impaired  to r a t s a n e s t h e t i z e d  I n both cases,  p e r f o r m a n c e when p r e s e n t e d  lowing passive avoidance t r a i n i n g .  prewith  t h e s e r i e s o f ECSs  still  1 o r 24 h o u r s b u t n o t 9 d a y s  fol-  T h i s f i n d i n g does n o t p r o v i d e  sup-  p o r t f o r a d i s t i n c t i o n b e t w e e n t h e g r a d i e n t s p r o d u c e d by a s i n g l e ECS and  a s e r i e s of ECSs.  T h e s e r e s u l t s w e r e t h e r e f o r e i n t e r p r e t e d as  s h o w i n g t h a t t h e l e n g t h o f t h e g r a d i e n t p r o d u c e d by a s i n g l e ECS i n a p a s s i v e a v o i d a n c e t a s k i s n o t a good e s t i m a t e required  f o r memory c o n s o l i d a t i o n .  c o n s o l i d a t i o n appears t o continue  o f t h e d u r a t i o n of time  I n t h i s passive avoidance f o r a p e r i o d of a t l e a s t  task,  several  d a y s , w h i l e t h e g r a d i e n t p r o d u c e d by a s i n g l e ECS was l e s s t h a n 1 h o u r . I n the t h i r d  e x p e r i m e n t , r a t s were t r a i n e d on a o n e - t r i a l a p p e t i -  t i v e taste and t h e n p r e s e n t e d  w i t h e i t h e r f i v e ECSs s p a c e d 1 m i n u t e  a p a r t , o r a s i n g l e ECS of 0.5 s e c o n d s o r 2.5 s e c o n d s d u r a t i o n . trast  to the r e s u l t s  i n the p a s s i v e a v o i d a n c e t a s k , the f i v e  spaced 1 minute a p a r t d i d not produce a l o n g e r g r a d i e n t ECS of e i t h e r 0.5 o r 2.5 s e c o n d s d u r a t i o n . p a i r e d p e r f o r m a n c e when p r e s e n t e d training.  A l l three  c o n s o l i d a t i o n processes  treatments  im-  after  f o r the d i f f e r e n t e f f e c t s of  the s e r i e s o f ECSs i n the two t a s k s a r e c o n s i d e r e d , that t h i s d i f f e r e n c e probably  ECSs  than a s i n g l e  15 s e c o n d s b u t n o t 1 hour  Several possible explanations  I n con-  and i t i s c o n c l u d e d  r e f l e c t s d i f f e r e n c e s between t h e memory  i n t h e two t a s k s .  Supervisor_  iv  TABLE OF CONTENTS Page ABSTRACT  i i  TABLE OF CONTENTS  iv  L I S T OF TABLES  v i  L I S T OF FIGURES  v i i  ACKNOWLEDGEMENTS  viii  INTRODUCTION  1  Memory C o n s o l i d a t i o n T h e o r y R a t i o n a l e f o r Using One-Trial Learning Procedures I n v e s t i g a t e Retrograde Amnesia Alternatives  1 to  t o the C o n s o l i d a t i o n I n t e r p r e t a t i o n of  ECS G r a d i e n t s ECS G r a d i e n t s and t h e D u r a t i o n of Memory C o n s o l i d a t i o n Length  3  o f ECS G r a d i e n t s  9 15 18  Two P o s s i b l e R e l a t i o n s h i p s Between t h e L e n g t h of ECS G r a d i e n t s and t h e D u r a t i o n o f Memory C o n s o l i d a t i o n  21  M u l t i p l e ECSs  23  Summary and R a t i o n a l e of t h e P r e s e n t I n v e s t i g a t i o n  26  EXPERIMENT 1:  THE EFFECT OF A SERIES OF ECSS ON RETENTION OF A PASSIVE AVOIDANCE RESPONSE  Method.  30 30  Subjects  30  Surgery Apparatus T r a i n i n g Procedure Experimental Conditions  30 31 32 33  B e h a v i o r a l Observations Histology  41 •  Discussion EXPERIMENT 2:  41 42  THE EFFECT OF PRESENTING A SERIES OF ECSS TO ANESTHETIZED ANIMALS  43  Method  44  Results B e h a v i o r a l Observations Discussion  46 46 47  EXPERIMENT 3:  EFFECT OF A SERIES OF ECSS ON AN APPETITIVE RESPONSE ACQUIRED IN A SINGLE TRIAL  51  Method  51  Results  53  Discussion  56  GENERAL DISCUSSION ECS Gradients and the D u r a t i o n of Memory C o n s o l i d a t i o n P a s s i v e Avoidance - A p p e t i t i v e Task D i f f e r e n c e s The E f f e c t of ECS on the C o n s o l i d a t i o n Process  58 58 ...61 66  CONCLUSIONS  74  REFERENCES  75  APPENDICES  84  vi  LIST OF TABLES  Table 1  2  3  Page The Number of Subjects Experiment 1  i n Each Treatment C o n d i t i o n i n 35  Drinking Latencies f o r the Groups i n Experiment 1 Which Did Not Receive ECS  38  Number of L i c k s a t the Empty Water Spout on the Test Day f o r the Groups i n Experiment 3  54  vii  L I S T OF FIGURES  Figure 1  2  Page M e d i a n D r i n k i n g L a t e n c i e s f o r t h e Groups R e c e i v i n g P a s s i v e A v o i d a n c e T r a i n i n g F o l l o w e d By One of t h e T h r e e ECS T r e a t m e n t s M e d i a n D r i n k i n g L a t e n c i e s f o r t h e Groups R e c e i v i n g 5 ECSs Spaced 1 M i n u t e A p a r t Under E t h e r o r Sodium P e n t o b a r b i t a l Anesthesia Following Passive Avoidance Training  40  48  ACKNOWLEDGEMENTS  I wish to thank Dr. David A l b e r t f o r h i s advice and a s s i s t a n c e throughout the course of t h i s i n v e s t i g a t i o n . I would a l s o l i k e t o acknowledge the u s e f u l c r i t i c i s m s of Fred Madryga, Chun Mah, Len S t o r l e i n and Svavar Tryggvason i n the e a r l y stages of t h i s  investi-  g a t i o n and the a s s i s t a n c e of Dr. John P i n e l i n the p r e p a r a t i o n of the t h e s i s .  This r e s e a r c h was supported by grants t o Dr. A l b e r t from  the N a t i o n a l Research C o u n c i l of Canada (APA-192).  Memory C o n s o l i d a t i o n T h e o r y  The  possibility  l e a r n i n g i n order and list  t h a t memories r e q u i r e a p e r i o d o f t i m e f o l l o w i n g  t o be p r o p e r l y  P i l z e c k e r (1900).  s t o r e d was f i r s t  They o b s e r v e d  o f words s h o r t l y a f t e r a f i r s t  the f i r s t  list.  the second l i s t ,  s u g g e s t e d by M u l l e r  t h a t humans l e a r n i n g a s e c o n d list  showed i m p a i r e d  r e t e n t i o n of  As an e x p l a n a t i o n f o r t h e r e t r o a c t i v e i n t e r f e r e n c e o f t h e y s u g g e s t e d t h a t memories r e q u i r e d a p e r i o d o f  time f o l l o w i n g l e a r n i n g i n order f o r m , and t h a t a n y d i s t u r b a n c e  t o be s t o r e d  during  i n their f i n a l ,  permanent  t h i s time might prevent the  memories f r o m becoming p r o p e r l y s t o r e d .  They i n t r o d u c e d  t h e term  "memory c o n s o l i d a t i o n " t o r e f e r t o t h e i n c r e a s i n g r e s i s t a n c e of t h e memories t o d i s r u p t i o n o v e r McDougall  time.  (1901) was t h e f i r s t  to suggest that the n o t i o n of  -memory c o n s o l i d a t i o n m i g h t a c c o u n t f o r t h e phenomenon o f r e t r o g r a d e a m n e s i a f o l l o w i n g head i n j u r y i n humans. p a t i e n t s r e p o r t an i n a b i l i t y  t o r e c a l l events which occurred  p e r i o d of time immediately preceding 1946  I n many c a s e s o f head  the i n j u r y  o r i e s of e v e n t s w h i c h o c c u r r e d t o be l o s t plained  T h e s e memory  o f t h e e v e n t t o t h e i n j u r y ; mem-  c l o s e r t o t h e i n j u r y a r e more  t h a n t h e memories o f more d i s t a n t e v e n t s .  the time-dependent c h a r a c t e r  1  during a  (see R u s s e l l & Nathan,  f o r an extensive examination of t h i s problem).  l o s s e s o f t e n depend on t h e c l o s e n e s s  injury,  likely  McDougall ex-  o f t h e s e memory l o s s e s i n terms  of  a memory c o n s o l i d a t i o n p r o c e s s .  Presumably,  memories w h i c h  were  l o s t w e r e t h o s e w h i c h had b e e n l e s s c o m p l e t e l y c o n s o l i d a t e d . P a t i e n t s r e c e i v i n g e l e c t r o c o n v u l s i v e shock a l s o been observed (Cronholm  therapy have  t o show a r e t r o g r a d e a m n e s i a f o r a n t e c e d e n t  & O t t o s o n , 1963;  W i l l i a m s , 1950;  these s t u d i e s , p a t i e n t s undergoing set  (ECS)  ECS  events  Zubin & B a r r e r a , 1941).  In  t h e r a p y were p r e s e n t e d w i t h a  o f s t i m u l i a t v a r i o u s i n t e r v a l s b e f o r e ECS.  I n g e n e r a l , the  showed t h a t r e t e n t i o n of t h e s t i m u l i p r e s e n t e d c l o s e s t t o t h e ECS  results was  most l i k e l y t o be d i s r u p t e d . Retrograde  a m n e s i a has a l s o b e e n i n v e s t i g a t e d  i n more c o n t r o l l e d  s e t t i n g s u s i n g e x p e r i m e n t a l a n i m a l s , u s u a l l y r a t s or m i c e (see L e w i s , 1969;  McGaugh & Dawson, 1971;  r e v i e w s of t h i s w o r k ) . g e n e r a l l y been found  shorter  S p e v a c k & S u b o s k i , 1969  to i m p a i r l a t e r performance  of a l e a r n e d  a r e u s u a l l y found  response  t o be g r a d e d , w i t h t h e  training-ECS delays producing l a r g e r impairments.  B e c a u s e of  t o t h e memory l o s s e s f o u n d w i t h humans, t h e s e g r a d i e n t s  a r e a l s o u s u a l l y i n t e r p r e t e d as r e f l e c t i n g r e t r o g r a d e  amnesias.  E x p e r i m e n t a l i n v e s t i g a t i o n s o f r e t r o g r a d e a m n e s i a have been c o n c e r n e d  have  t r a i n i n g , b u t n o t when d e l a y e d f o r a s u f f i -  These impairments  their similarity  for recent  I n t h e s e s t u d i e s , t r e a t m e n t s s u c h as ECS  'when p r e s e n t e d s o o n a f t e r c i e n t time.  and  w i t h two  issues.  F i r s t , do  largely  these g r a d i e n t s a c t u a l l y r e -  f l e c t d i s t u r b a n c e s of a memory c o n s o l i d a t i o n p r o c e s s ?  Second, assuming  t h e y do r e p r e s e n t d i s t u r b a n c e s o f memory c o n s o l i d a t i o n what d u r a t i o n of  time i s r e q u i r e d f o r the c o n s o l i d a t i o n p r o c e s s to r e a c h  N e i t h e r of these i s s u e s i s c o m p l e t e l y r e s o l v e d .  The  first  completion? i s s u e has  received  t h e most a t t e n t i o n , and a l t h o u g h  a number o f a d d i t i o n a l e x -  p l a n a t i o n s have b e e n o f f e r e d f o r t h e s e g r a d i e n t s , t h e r e i s s t i l l  a  s u b s t a n t i a l concensus i n f a v o r of t h e c o n s o l i d a t i o n i n t e r p r e t a t i o n . With respect  t o t h e s e c o n d i s s u e , i t h a s b e e n a common p r a c t i c e t o v i e w  the l e n g t h o f the g r a d i e n t  p r o d u c e d by ECS a s a n e s t i m a t e  of the dur-  a t i o n of t i m e r e q u i r e d f o r memory c o n s o l i d a t i o n t o be c o m p l e t e d , a l though r e c e n t The  f i n d i n g s s u g g e s t t h a t t h i s v i e w may n o t be c o r r e c t .  present  t h e s i s i s concerned w i t h the r e l a t i o n s h i p of the  l e n g t h o f t h e a m n e s i a g r a d i e n t p r o d u c e d b y ECS t o t h e d u r a t i o n o f t h e memory c o n s o l i d a t i o n p r o c e s s .  Before  d i r e c t l y considering  t i o n , t h e t r a i n i n g p r o c e d u r e s most w i d e l y used  p l a i n e d as d i s t u r b a n c e s  with  ques-  to i n v e s t i g a t e r e t r o -  g r a d e a m n e s i a w i l l be d e s c r i b e d , and a n a t t e m p t w i l l t h a t t h e ECS g r a d i e n t s o b t a i n e d  this  be made t o show  these procedures a r e best ex-  o f memory c o n s o l i d a t i o n .  R a t i o n a l e For Using  One-Trial Learning  Procedures  to I n v e s t i g a t e R e t r o g r a d e Amnesia Duncan (1949) p r o v i d e d performance of a l e a r n e d t r a i n i n g and ECS. giving 1 t r i a l  the f i r s t d e m o n s t r a t i o n of  impaired  r e s p o n s e w h i c h depended on t h e t i m e b e t w e e n  He t r a i n e d r a t s i n a one-way a v o i d a n c e a p p a r a t u s ,  per day.  Following  were g i v e n ECS e i t h e r 20 s e c , 4 h r s . , o r 14 h r s . l a t e r .  each d a i l y  40 s e c ,  trial,  60 s e c ,  separate  4 min.,  groups  15 m i n . ,  1 hr. ,  I m p a i r e d a c q u i s i t i o n was f o u n d i n t h e  g r o u p s g i v e n ECS a t 15 m i n u t e s o r l e s s a f t e r e a c h t r i a l . ment was g r a d e d , w i t h t h e s h o r t e s t t r a i n i n g - E C S  delays  The i m p a i r -  showing the  4 slowest  acquisition.  turbance  Duncan a t t r i b u t e d t h i s ECS g r a d i e n t  of memory c o n s o l i d a t i o n .  Coons and M i l l e r  (1960) r e p l i c a t e d Duncan's e x p e r i m e n t ,  made t h e a d d i t i o n a l o b s e r v a t i o n training-ECS behaviour  to a d i s -  that the animals  i n the s h o r t e s t  c o n d i t i o n s tended t o e x h i b i t a g r e a t d e a l of  (defecation).  emotional  On t h e b a s i s o f t h i s o b s e r v a t i o n ,  s u g g e s t e d t h a t ECS m i g h t h a v e a v e r s i v e e f f e c t s w h i c h c o u l d w i t h the a c q u i s i t i o n of the avoidance response. ministered f o l l o w i n g entry into  has  aversive effects,  r a t s were f i r s t avoid shock. reversed  I n order  interfere  S i n c e ECS was a d -  t o t h i s s i d e , thus  to test the p o s s i b i l i t y  decreasing t h a t ECS  they conducted a second experiment i n w h i c h  t r a i n e d t o r u n f r o m a s t a r t b o x t o a g o a l box t o  A f t e r a c q u i s i t i o n of t h i s r e s p o n s e , t h e c o n d i t i o n s w e r e  so t h a t t h e a n i m a l s  p r e v i o u s l y had b e e n " s a f e " . either  they  t h e n o n - s h o c k e d s i d e , any a v e r s i v e  e f f e c t s m i g h t h a v e become c o n d i t i o n e d the tendency t o a v o i d .  and  w e r e now s h o c k e d i n t h e g o a l b o x w h i c h ECS was a d m i n i s t e r e d  20 s e c , 60 s e c , o r 1 h r . a f t e r  Coons and M i l l e r  to s e p a r a t e  the shock i n the g o a l box.  f o u n d t h a t t h e 20-second g r o u p l e a r n e d  to avoid the  g o a l b o x f a s t e r t h a n t h e 60-second g r o u p , and t h a t b o t h o f l e a r n e d f a s t e r t h a n t h e 1-hour g r o u p .  groups  these  This gradient i s e x a c t l y the  o p p o s i t e o f t h a t w h i c h w o u l d be e x p e c t e d i f ECS w e r e d i s t u r b i n g memory c o n s o l i d a t i o n .  They s u g g e s t e d  t h a t ECS h a s a v e r s i v e e f f e c t s  w h i c h may summate w i t h t h e a v e r s i v e e f f e c t s o f t h e f o o t s h o c k . a r g u e d t h a t t h e ECS g r a d i e n t f o u n d by Duncan p r o b a b l y  They  reflects a  g r a d i e n t o f t h e a v e r s i v e e f f e c t s o f ECS, and n o t a g r a d i e n t o f a m n e s i a .  I n a n o t h e r a t t a c k on t h e c o n s o l i d a t i o n i n t e r p r e t a t i o n o f Duncan' f i n d i n g s , Adams and L e w i s (1962) showed t h a t a n i m a l s when p l a c e d ECSs.  became i m m o b i l e  i n an a p p a r a t u s i n w h i c h t h e y had r e c e i v e d a s e r i e s o f  They s u g g e s t e d  convulsions"  that repeated  t o be c o n d i t i o n e d  ECS t r e a t m e n t s  caused  t o t h e p l a c e w h e r e ECS was  I f f r a c t i o n a l c o n v u l s i o n s were c o n d i t i o n e d  atus  training,  f o r t h e g r a d e d a p p e a r a n c e o f t h e ECS d e f i c i t s . Suboski  (1969) h a v e p o i n t e d  explained  acquisition.  t o become c o n d i t i o n e d  i n t h e g r o u p s g i v e n ECS s o o n e r a f t e r  situation,  a n d , i n Duncan's  experiment, such i n h i b i t i o n would appear as i m p a i r e d w o u l d be more l i k e l y  administered  to the t r a i n i n g  t h e y m i g h t be e x p e c t e d t o i n h i b i t l a t e r r e s p o n d i n g ,  Convulsions  "fractional  to the appar-  thereby  accounting  However, S p e v a c k and  o u t t h a t Adams and L e w i s '  r e s u l t s c a n be  s i m p l y by t h e a v e r s i v e e f f e c t s o f a s e r i e s o f ECSs.  o f t e n become i m m o b i l e when c o n f r o n t e d  with stimuli previously  i a t e d w i t h aversive s t i m u l a t i o n (Estes & Skinner, t h e r e i s no d i r e c t e v i d e n c e s u p p o r t i n g  1941).  Rats assoc-  Moreover,  t h e c l a i m t h a t an ECS-produced  c o n v u l s i o n c a n f u n c t i o n a s an u n c o n d i t i o n e d  stimulus  (Kent, Hawkins, &  Sharpe, 1960). To a v o i d  t h e c r i t i c i s m s r a i s e d by Coons and M i l l e r  Adams and L e w i s (1962) , e x p e r i m e n t e r s avoidance t r a i n i n g procedures consolidation. footshock,  I n these  (1960) and  began u s i n g o n e - t r i a l  passive  (Hudson, 1950) t o i n v e s t i g a t e memory  tasks, animals  a r e p u n i s h e d , u s u a l l y by  f o r m a k i n g a r e s p o n s e s u c h as s t e p p i n g down f r o m a p l a t -  f o r m , o r p r e s s i n g a b a r . T h e r e a r e two a d v a n t a g e s o f o n e - t r i a l ive avoidance tasks.  F i r s t , since the animal  pass-  l e a r n s to i n h i b i t a  p u n i s h e d r e s p o n s e , any  a v e r s i v e e f f e c t s of ECS  summate w i t h  the  e f f e c t s of t h e s h o c k t o i n c r e a s e t h e l a t e n c y t o p e r f o r m t h e However, i f ECS w i l l continue testing.  response.  p r o d u c e s a l o s s of memory f o r t h e f o o t s h o c k ,  the  t o p e r f o r m t h e r e s p o n s e w i t h a s h o r t l a t e n c y on  has  was  involves  an a d d i t i o n a l a d v a n t a g e of o n l y r e q u i r i n g  the a d m i n i s t r a t i o n of a s i n g l e ECS i n w h i c h ECS  animal  later  Secondly, the p a s s i v e avoidance t a s k , s i n c e i t o n l y  a single training t r i a l ,  aversive  administered  i n c o n t r a s t t o Duncan's p r o c e d u r e  f o l l o w i n g each d a i l y  a d v a n t a g e b e c a u s e a s i n g l e ECS  trial.  This  does n o t p r o d u c e as s t r o n g  i s an  aversive  e f f e c t s as m u l t i p l e ECSs ( H u d s p e t h , McGaugh, & Thompson, 1 9 6 4 ) . A s i n g l e ECS  has  g e n e r a l l y been found to produce time-dependent  i m p a i r m e n t s of p a s s i v e a v o i d a n c e r e s p o n s e s H e r i o t & C o l e m a n , 1962; McGaugh, 1966; others). a bar  For  K i n g , 1967;  M i l l e r , 1968;  administered  t h r o u g h the b a r .  ECS  e i t h e r 1, 7,  26,  t r o l group r e c e i v e d  t h e a n i m a l s were r e t u r n e d 10-minute s e s s i o n was  acquired, a punishing  S e p a r a t e g r o u p s of r a t s  the p u n i s h i n g  shock.  t o t h e b a r and  recorded.  The  with  received  the  delays.  The  A  con-  g r o u p s g i v e n ECS  m i n u t e s a f t e r the p u n i s h m e n t showed s i g n i f i c a n t l y  a t 1, 7,  later,  in a bar  t h i s i m p a i r m e n t was  i n a graded f a s h i o n , the g r e a t e s t a t t e n u a t i o n  the s h o r t e s t ECS  press  Twenty-four hours  punishment impaired  and  shock  t h e number o f p r e s s e s  p r e s s i n g r e s p o n s e i n the c o n t r o l g r o u p , b u t u a t e d by ECS  1965;  60 or 180 m i n u t e s a f t e r t h e p u n i s h m e n t . only  1966;  Coleman (1962) t r a i n e d r a t s t o  A f t e r t h i s r e s p o n s e was  was  1965;  Kopp, Bohdenecky, & J a r v i k ,  Quartermain, P a o l i n o , & M i l l e r ,  e x a m p l e , H e r i o t and  f o r food.  (Chorover & S c h i l l e r ,  atten-  appearing 26,  l e s s impairment  or  60  than  7 the  controls. R e c e n t l y , s e v e r a l other o n e - t r i a l l e a r n i n g procedures have been  used to i n v e s t i g a t e r e t r o g r a d e amnesia. t r a i n i n g , i n v o l v e s an i n c r e a s e  One  procedure, " a p p e t i t i v e "  i n the s t r e n g t h  of an a p p e t i t i v e l y  motivated response as the r e s u l t of a s i n g l e experience w i t h water.  For example, Tenen (1965a) allowed t h i r s t y r a t s to f i n d water  i n a previously  empty c u l de sac.  i e n c e , the r a t s showed an increased c u l de sac on a l a t e r t e s t s e s s i o n . avoidance" t r a i n i n g . one  As a r e s u l t of t h i s s i n g l e expertendency to r e t u r n to the empty Another procedure i s  "discriminated  I n t h i s paradigm two responses are a v a i l a b l e  of them i s followed  by punishment.  A s i n g l e punishment i s s u f f i -  c i e n t to e s t a b l i s h a preference f o r the other response.  For  example,  P f i n g s t and K i n g (1969) t r a i n e d hungry r a t s i n a T-maze which had a v a i l a b l e i n both arms.  of the maze.  showed an increased  administered upon e n t e r i n g  As a r e s u l t of t h i s s i n g l e punishment, the r a t s preference f o r the other arm  of the maze.  a v e r s i v e and  amnesic e f f e c t s are not opposed i n these two  i t generally  p o s s i b l e to detect the presence of a v e r s i v e  v i d i n g the response b a s e l i n e p r e s e n t i n g ECS  food  A f t e r the r a t s were accustomed to running  the maze f o r food, a p u n i s h i n g shock was one arm  and  Although  tasks, i t effects.  Pro-  i s s u f f i c i e n t l y h i g h before t r a i n i n g ,  immediately a f t e r making the response i n q u e s t i o n  should produce a decreased tendency to make t h i s response on l a t e r testing.  While t h i s c o n t r o l i s not completely s a t i s f a c t o r y , a number  of experiments have observed time-dependent e f f e c t s of ECS not a p p a r e n t l y due  to a v e r s i v e  e f f e c t s of ECS  which are  w i t h both a p p e t i t i v e  ( P i n e l , 1 9 6 9 ; S c h i l l e r & C h o r o v e r , 1967; T e n e n , 1 9 6 5 a , 1965b) and d i s criminated avoidance procedures  (Carew,  1970; P f i n g s t & K i n g , 1 9 6 9 ) .  O n e - t r i a l l e a r n i n g p r o c e d u r e s have b e e n p o p u l a r n o t o n l y they p e r m i t an assessment  because  of r e t r o g r a d e amnesia w i t h o u t the c o n f o u n d i n g  f a c t o r of a v e r s i v e e f f e c t s , b u t a l s o because  they p e r m i t a c l e a r de-  t e r m i n a t i o n o f t h e t r a i n i n g - E C S i n t e r v a l and c o n s e q u e n t l y a more p r e c i s e e s t i m a t e o f t h e d u r a t i o n o f memory c o n s o l i d a t i o n .  This i s an  advantage  o v e r some o t h e r p r o c e d u r e s i n w h i c h a s e r i e s o f massed  were used  ( G e r b r a n d t , B u r e s o v a , & B u r e s , 1966; Thompson & P e n n i n g t o n ,  1957).  trials  A l t h o u g h o n l y a s i n g l e a d m i n i s t r a t i o n o f ECS was r e q u i r e d i n  t h e s e t a s k s , s p e c i f i c a t i o n o f t h e t i m e d u r i n g t r a i n i n g a t w h i c h memory c o n s o l i d a t i o n b e g a n was n o t p o s s i b l e s i n c e c o n s o l i d a t i o n may h a v e s t a r t e d a t any t i m e d u r i n g t h e t r a i n i n g I t i s now w e l l e s t a b l i s h e d  period.  t h a t time-dependent  impairments of  -performance c a n be p r o d u c e d b y ECS i n a v a r i e t y o f t r a i n i n g Many o t h e r t r e a t m e n t s have a l s o b e e n f o u n d deficits.  to produce  situations.  time-dependent  These i n c l u d e e t h e r and p e n t o b a r b i t a l a n e s t h e s i a ( P e a r l m a n ,  S h a r p l e s s , & J a r v i k , 1 9 6 1 ) , CO2 ( P a o l i n o , Q u a r t e r m a i n , & M i l l e r , cooling  ( R i c c i o , Hodges, & R a n d a l l , 1 9 6 8 ) , and c o r t i c a l s p r e a d i n g  d e p r e s s i o n (Bures & Buresova, 1963). i n t e r p r e t e d as r e t r o g r a d e a m n e s i a , being a t t r i b u t e d  These i m p a i r m e n t s a r e f r e q u e n t l y  t h e i r t e m p o r a l l y graded  nature  t o a n u n d e r l y i n g memory c o n s o l i d a t i o n p r o c e s s .  R e c e n t l y , a number o f a l t e r n a t i v e e x p l a n a t i o n s have a l s o offered  1966),  f o r these gradients.  been  Most o f t h e s e a l t e r n a t i v e e x p l a n a t i o n s  a r e s p e c i f i c a l l y d i r e c t e d a t g r a d i e n t s o b t a i n e d w i t h a s i n g l e ECS i n  9 a passive  avoidance t r a i n i n g  s i t u a t i o n which  i s t h e most p o p u l a r  digm f o r i n v e s t i g a t i n g memory c o n s o l i d a t i o n . however, a l s o a p p l y other  treatments  i n other  Alternatives Pinel  i n v a r y i n g degrees  and C o o p e r  (1966) , w h i l e  examining  various  times a f t e r  referred  to the gradients  This  training,  improvement  found  that passive  i n passive  t o as t h e " i n c u b a t i o n " e f f e c t  1969; P i n e l ,  that rather  ECS c o u l d be v i e w e d  bation hypothesis. 1 minute) r e f l e c t  have b e e n o b t a i n e d appetitive  (Herz,  discriminated point  improved  i n many  1970) p a s s i v e  t h e time c o u r s e  avoidance  tasks.  of improvement i n  of t h e i r  ECS g r a d i e n t . process,  h a l t i n g the i n c u b a t i o n of the r e s p o n s e .  that b r i e f  amnesia, w h i l e They c l a i m e d  i n the other 1969; P i n e l ,  avoidance  of a  time has been  (1969) h a v e f u r t h e r e l a b o r a t e d  retrograde  Gradients  1968; McGaugh, 1966) b u t n o t a l l  to the length  They p r o p o s e d  h a l t i n g of i n c u b a t i o n .  avoidance  than d i s r u p t i n g a c o n s o l i d a t i o n  as s i m p l y  Spevack and S u b o s k i  the  that  avoidance corresponded  They s u g g e s t e d  with  of r a t s a t  and h a s b e e n f o u n d  ( B a i l e y , Garman, & C h e r k i n ,  (1966) n o t e d  groups  avoidance over  & Curtis,  P i n e l and Cooper  the s t r e n g t h  different  (Irwin, Banuazizi, Kalsner,  passive  obtained  t o The C o n s o l i d a t i o n I n t e r p r e t a t i o n o f ECS  avoidance response by t e s t i n g  time.  explanations,  situations.  passive  over  These  para-  one-trial  ECS g r a d i e n t s longer  periods  that only b r i e f  & Chorover,  (Carew, 1970; P f i n g s t & K i n g , i n these  incu-  (less  than  a r e due t o  gradients  l e a r n i n g procedures,  1969; S c h i l l e r  o u t t h a t i n c u b a t i o n does n o t a p p e a r  this  namely  1967) and  1 9 6 9 ) , and t h e y  situations  (Pinel,  1969; and  Suboskl, Suboski's  Spevack, L i t n e r , & Beaumaster, 1969). hypothesis  Tenen (1965b) has task.  However, S p e v a c k  i s not c o n s i s t e n t w i t h a l l the a v a i l a b l e d a t a .  r e p o r t e d an ECS  g r a d i e n t of 3 h o u r s i n an a p p e t i t i v e  In a d d i t i o n , s e v e r a l passive avoidance tasks i n which  g r a d i e n t s w e r e f o u n d do  not  long  show i n c u b a t i o n ( B a i l e y e t a l . , 1969;  Pinel,  1970). Weiskrantz of treatments ients ECS  (1966) has  s u c h as ECS.  p r o p o s e d an a l t e r n a t i v e m o d e l f o r t h e e f f e c t s He  s u g g e s t s t h a t w h i l e v e r y s h o r t ECS  (20 s e c o n d s ) m i g h t r e f l e c t d i s t u r b a n c e s  of c o n s o l i d a t i o n , l o n g e r  g r a d i e n t s r e f l e c t i m p a i r m e n t s of memory r e t r i e v a l .  t h a t memories c o n t i n u e  He  assumes  t o i n c r e a s e i n s t r e n g t h o v e r a p e r i o d of weeks  ( i n the s e n s e of the n e u r a l s i g n a l u n d e r l y i n g memory b e c o m i n g t o p r o d u c e a l a r g e r " s i g n a l to n o i s e " r a t i o ) . treatments  s u c h as ECS  trace continues  sufficiently  a number of  In fact,  As  w i l l be  i n v e s t i g a t o r s (e.g., Z i n k i n & M i l l e r ,  be more i m p o r t a n t  out  T h i s model p r e d i c t s temporary, d i s a p -  t e m p o r a r y d e f i c i t s have b e e n f o u n d  t h i s model a l s o p r e d i c t s t h a t the should  the  to i n c r e a s e i n s t r e n g t h , i t e v e n t u a l l y stands  f r o m t h e n o i s e l e v e l to be r e c a l l e d .  time.  a l s o assumes t h a t  the s i g n a l to n o i s e r a t i o .  t h a t p e r f o r m a n c e d e f i c i t s p r o d u c e d by ECS pearing with  He  stronger  introduce a d d i t i o n a l noise which prevents  »recall of weaker t r a c e s by d e c r e a s i n g -the  grad-  1967).  by  However,  t i m e between t r a i n i n g and  testing  t h a n the i n t e r v a l b e t w e e n t r a i n i n g and  ECS,  a f i n d i n g t h a t i s not c o n s i s t e n t w i t h the a v a i l a b l e d a t a . N i e l s o n (1968) a t t e m p t e d to e x p l a i n ECS through suggesting  e f f e c t s on  that.ECS produces b r a i n e x c i t a b i l i t y  performance changes.  These changes w e r e t h o u g h t t o i m p a i r r e c a l l mechanism.  He s u g g e s t e d t h a t p e r f o r m a n c e  a f t e r ECS b e c a u s e training.  through a "state-dependent"  i s impaired  f o r up t o 4 d a y s  t h e b r a i n i s i n a d i f f e r e n t s t a t e t h a n i t was  Nielson provided  in brain excitability  some d i r e c t e v i d e n c e f o r t e m p o r a r y  as a r e s u l t o f ECS.  4 days.  response increased  N i e l s o n ' s model,  changes  He showed t h a t t h e i n t e n -  s i t y of s u b c o r t i c a l e l e c t r i c a l s t i m u l a t i o n n e c e s s a r y t o e l i c i t conditioned  during  a  f o l l o w i n g ECS and t h e n d e c r e a s e d o v e r  l i k e ' W e i s k r a n t z ' s , p r e d i c t s that the im-  p a i r m e n t p r o d u c e d by ECS w o u l d  o n l y be t e m p o r a r y .  However, N i e l s o n  makes no a t t e m p t t o a c c o u n t f o r t h e t i m e - d e p e n d e n t  n a t u r e of these  impairments. P o s l u n s and V a n d e r w o l f effects:  a d i s r u p t i o n o f c o n s o l i d a t i o n and an i m p a i r m e n t o f r e s p o n s e  inhibition.  T h e s e two e f f e c t s a r e v i e w e d a s c o m b i n i n g i n t a s k s  requiring immobility gradients  (1970) h a v e s u g g e s t e d t h a t ECS h a s two  ( s u c h as t h e p a s s i v e a v o i d a n c e ) t o p r o d u c e  than i n tasks not r e q u i r i n g immobility.  c l e a r f r o m t h e i r m o d e l how a t i m e - d e p e n d e n t b i n e w i t h a non-time-dependent longer  time-dependent  longer  However, i t i s n o t  e f f e c t (amnesia) c a n com-  effect (disinhibition)  to produce a  effect.  I n a d d i t i o n t o t h e t h e o r e t i c a l m o d e l s w h i c h have been p r e s e n t e d as a l t e r n a t i v e s t o t h e c o n s o l i d a t i o n h y p o t h e s i s , recent  evidence which i s d i f f i c u l t  there  to reconcile with  i s a l s o some  t h e memory c o n -  s o l i d a t i o n i n t e r p r e t a t i o n , b u t w h i c h has n o t y e t g i v e n r i s e quate a l t e r n a t i v e e x p l a n a t i o n s .  S e v e r a l s t u d i e s have  i m p a i r m e n t s of p e r f o r m a n c e w h i c h a r e n o t d e p e n d e n t  t o ade-  demonstrated  on t h e t i m e b e t w e e n  t r a i n i n g and ECS, b u t r a t h e r on t h e t i m e b e t w e e n some o t h e r e v e n t and ECS.  S c h n e i d e r and Sherman (1968) p r e s e n t e d ECS  to r a t s e i t h e r  0.5  s e c o n d s , 30 s e c o n d s , o r 6 h o u r s a f t e r a s i n g l e p a s s i v e a v o i d a n c e training t r i a l .  They f o u n d t h a t p e r f o r m a n c e of t h e p a s s i v e a v o i d a n c e  r e s p o n s e was  i m p a i r e d i n t h e 0.5  conditions.  They f o u n d , h o w e v e r , t h a t i f a n a d d i t i o n a l , n o n c o n t i n g e n t  f o o t s h o c k was ECS,  d e l i v e r e d 0.5  p e r f o r m a n c e was  s e c o n d b u t n o t 30 s e c o n d o r 6 h o u r  s e c o n d s b e f o r e t h e 30 s e c o n d o r 6 h o u r  also impaired.  M i s a n i n , M i l l e r , and L e w i s ( 1 9 6 8 ) . e m o t i o n a l r e s p o n s e (CER) showed t h a t i f ECS  They e s t a b l i s h e d a  g i v e n 24 h o u r s a f t e r t r a i n i n g was impaired.  by  conditioned  t o a l i g h t by p a i r i n g i t w i t h s h o c k ,  l i g h t , p e r f o r m a n c e o f t h e CER was performance  S i m i l a r f i n d i n g s were r e p o r t e d  and  p r e c e d e d by  the  I n both these cases,  i m p a i r m e n t s w e r e r e p o r t e d w h i c h w e r e dependent  n o t on t h e  t i m e b e t w e e n t r a i n i n g and ECS, b u t r a t h e r on t h e t i m e b e t w e e n some o t h e r e v e n t s u c h as f o o t s h o c k o r l i g h t and ECS.  These f i n d i n g s  be d e s c r i b e d as r e f l e c t i n g t h e " r e i n s t a t e m e n t " o f t h e a b i l i t y to d i s r u p t  of  ECS  t h a t t h e p a i r i n g of  ECS  performance.  S c h n e i d e r and Sherman (1968) c o n t e n d e d and f o o t s h o c k - p r o d u c e d a r o u s a l c a u s e d " a f t e r  e f f e c t s " which impaired  t h e l a t e r p e r f o r m a n c e of t h e p a s s i v e a v o i d a n c e r e s p o n s e . al.  can  Misanin et  ( 1 9 6 8 ) , on t h e o t h e r h a n d , s u g g e s t e d t h a t p r e s e n t a t i o n o f t h e  l i g h t c a u s e d t h e memory t o be r e c a l l e d , and t h u s t o e n t e r a s t a t e i n w h i c h i t was more s u s c e p t i b l e t o d i s r u p t i o n .  N e i t h e r of t h e s e e x -  p l a n a t i o n s i s v e r y e x p l i c i t , and n e i t h e r has b e e n d i r e c t l y s u p p o r t e d . Moreover,  t h e s e phenomena a r e d i f f i c u l t  to r e p l i c a t e .  Banker, Hunt,  and  Pagano ( 1 9 6 9 ) , Dawson and  (19.70), and the f i r s t  L e e - T e n g (1970a) h a v e a l l f a i l e d  two  g o l d f i s h and  to o b t a i n  Klinger  (1969) h a v e r e p o r t e d  a one-way a v o i d a n c e t r a i n i n g p r o c e d u r e .  number of a g e n t s w h i c h w o u l d n o r m a l l y be performance.  successful  D e V i e t t i and  r e p l i c a t i o n of  "reinstatement e f f e c t " .  The  learned.  ECS  aroused, not The problem.  r a t s and  procedure.  (Howard & M e y e r ,  f o l l o w i n g c r i t e r i o n on o n l y was  t h e ECS,  same t y p e of m o t i v a t i o n  on  the n a t u r e of the age  of  i n t e r p r e t a t i o n of None of  to  but as  other the  third the  discriminations  third  discrimination  o t h e r d i s c r i m i n a t i o n was  the  the  the m o t i v a t i o n a l  s t a t e most  the  first  gradients  be-  recently  memories.  the r e i n s t a t e m e n t e f f e c t i s a v e r y r e a l  e x p l a n a t i o n s so f a r o f f e r e d  f i n d i n g s are d i f f i c u l t  the on  the  p e r f o r m a n c e of  p l a i n a l l the d a t a i n c l u d i n g t h e d i f f i c u l t y w i t h  t a t i o n of ECS  a CER  seemed t o d i s r u p t a c l a s s of r e s p o n s e s , i m p a i r m e n t  i n g d e p e n d e n t on  a  a  t h a t not  w e r e a l s o i m p a i r e d , e v e n when the  to  L a r s o n (1971) h a v e a l s o r e p o r t e d  g i v e n ECS  t h i r d d i s c r i m i n a t i o n i m p a i r e d by the  found to a l l o w  that bears s u b s t a n t i a l s i m i l a r i t y  results indicated  which involved  Re-exposure  I n these e x p e r i m e n t s , r a t s were t r a i n e d  t h r e e d i s c r i m i n a t i o n s , and task.  using  to  r e c e n t l y been r e p o r t e d  R o b b i n s & M e y e r , 1970)  How-  i n e f f e c t i v e at t h i s time  this effect using  A n o t h e r f i n d i n g has 1971;  these e f f e c t s ,  a similar finding  t r a i n i n g a p p a r a t u s 24 h o u r s a f t e r t r a i n i n g was  impair  Albert  experiments being attempts at exact r e p l i c a t i o n .  e v e r , D a v i s and  the  McGaugh ( 1 9 6 9 ) , J a m i e s o n and  to r e c o n c i l e w i t h since  the  these gradients  can  adequately  replication.  consolidation can  ex-  These  interpre-  be o b t a i n e d  at  14 t i m e s when c o n s o l i d a t i o n i s p r e s u m a b l y n o t o c c u r r i n g .  However, i t i s  important to point out that these data a r e not n e c e s s a r i l y with  the notion  t h a t ECS p r e s e n t e d s h o r t l y a f t e r t r a i n i n g  d i s r u p t s a memory c o n s o l i d a t i o n p r o c e s s . that consolidated  memories c a n become s u s c e p t i b l e t o d i s r u p t i o n f o r f o r most ECS g r a d i e n t s .  T h e r e i s a n o t h e r f i n d i n g w h i c h r a i s e s some q u e s t i o n i n t e r p r e t a t i o n o f ECS g r a d i e n t s .  f o l l o w e d w i t h i n 0.5 s e c o n d s a f t e r a f o o t s h o c k , seizure discharge  about the  C h o r o v e r and D e L u c a (1969) r e c e n t l y  f o u n d t h a t ECS d i d n o t p r o d u c e s e i z u r e d i s c h a r g e  i n the cortex  i f i t  b u t i t d i d produce  i f d e l a y e d f o r 30 s e c o n d s o r i f ECS was n o t p r e -  ceded by f o o t s h o c k .  This  f i n d i n g i n d i c a t e s that the s e i z u r e  by ECS i s n o t of a c o n s t a n t s e n t a t i o n of f o o t s h o c k .  f o r m , b u t c a n be m o d i f i e d  Since  footshock  produced  by p r i o r  pre-  i s g e n e r a l l y used i n p a s s i v e  -avoidance t r a i n i n g , t h i s f i n d i n g r a i s e s t h e p o s s i b i l i t y  rather  normally  I t i s p o s s i b l e , f o r example,  some r e a s o n q u i t e d i f f e r e n t f r o m t h a t r e s p o n s i b l e  gradients  inconsistent  t h a t ECS  m i g h t be due t o a change i n t h e s e i z u r e p r o d u c e d by ECS,  t h a n a change i n t h e u n d e r l y i n g Processes other  consolidation  process.  than'memory c o n s o l i d a t i o n h a v e n o t b e e n shown  t o a d e q u a t e l y a c c o u n t f o r most ECS g r a d i e n t s , a n d , a l t h o u g h some a s p e c t s of ECS g r a d i e n t s  are not completely  of memory c o n s o l i d a t i o n s t i l l While there  understood, a  a p p e a r s t o be t h e b e s t  explanation.  i s no d i r e c t way o f d e m o n s t r a t i n g t h a t t h e s e  r e f l e c t memory c o n s o l i d a t i o n , t h e r e  disturbance  gradients  i s i n d i r e c t s u p p o r t f o r t h e assump-  t i o n t h a t t h e y r e f l e c t memory l o s s e s r a t h e r Such s u p p o r t comes from t h e i r s i m i l a r i t y  t h a n some o t h e r  t o human r e t r o g r a d e  disturbance. amnesia,  as w e l l a s f r o m t h e f a c t t h a t t h e y a r e o b t a i n e d  i n a v a r i e t y of s i t -  u a t i o n s and w i t h a number o f d i f f e r e n t t r e a t m e n t s . g r a d i e n t s r e f l e c t memory l o s s , t h e b e s t  Assuming t h a t the  explanation for their  tempor-  a l l y g r a d e d c h a r a c t e r seems t o b e t h a t t h e y r e f l e c t a n u n d e r l y i n g s o l i d a t i o n process. as  However, b e c a u s e t h e r e i s s t i l l  con-  some u n c e r t a i n t y  t o w h e t h e r t h e d e f i c i t s a t r e t e s t a r e on r e t e n t i o n o r p e r f o r m a n c e ,  the t e r m "ECS g r a d i e n t " w i l l be used i n s t e a d o f t h e more common " a m n e s i a g r a d i e n t " t o r e f e r t o a n i m p a i r m e n t of a l e a r n e d r e s p o n s e w h i c h i s p r o d u c e d b y ECS and w h i c h d e p e n d s , i n a g r a d e d f a s h i o n , on t h e t i m e b e t w e e n t r a i n i n g and ECS. is  an i n t e r p r e t a t i o n of t h e g r a d i e n t and n o t j u s t a d e s c r i p t i o n .  ECS  Gradients  and t h e D u r a t i o n o f Memory C o n s o l i d a t i o n  This s e c t i o n w i l l ECS  T h i s i s done t o e m p h a s i z e t h a t " a m n e s i a "  f i r s t consider  t h e r e a s o n s why t h e l e n g t h s o f  g r a d i e n t s have b e e n i n t e r p r e t e d as r e f l e c t i n g  consolidation.  Recent evidence w i l l  the d u r a t i o n of  t h e n be p r e s e n t e d  showing  the l e n g t h o f t h e g r a d i e n t p r o d u c e d b y ECS i s n o t c o n s t a n t to  a limited  e x t e n t on ECS c u r r e n t p a r a m e t e r s .  the f a c t  i s completely  t h a t a s i n g l e ECS p r o -  duces o n l y a l i m i t e d p h y s i o l o g i c a l d i s t u r b a n c e . p l o r i n g t h i s question, the p o s s i b i l i t y  b u t depends  This l i m i t might r e -  f l e c t t h e p o i n t a t w h i c h t h e memory n o t y e t c o n s o l i d a t e d d i s t u r b e d , o r i t may s i m p l y r e f l e c t  that  As a means o f e x -  t h a t a s e r i e s o f ECS  treatments  may p r o d u c e a l o n g e r g r a d i e n t t h a n a s i n g l e ECS w i l l be examined. The  d u r a t i o n of t i m e r e q u i r e d f o r memory c o n s o l i d a t i o n has  f r e q u e n t l y been e s t i m a t e d  f r o m t h e l e n g t h o f t h e ECS g r a d i e n t .  The  r e a s o n f o r c h o o s i n g ECS  f o r t h i s p u r p o s e seems t o be b a s e d , a t l e a s t  i n p a r t , on t h e v i e w t h a t ECS m a x i m a l l y d i s r u p t s t h e memory c o n s o l i d a t i o n process.  Such a v i e w i s s u p p o r t e d by two w i d e l y h e l d a s s u m p t i o n s .  F i r s t , c o n s o l i d a t i o n has b e e n assumed t o i n v o l v e p a t t e r n e d  neural  f i r i n g w h i c h p e r s i s t s f o r a p e r i o d of t i m e f o l l o w i n g l e a r n i n g and w h i c h i s n e c e s s a r y f o r memories t o be p e r m a n e n t l y s t o r e d Hebb, 1949; J o h n , 1 9 6 7 ) . maximal d i s t u r b a n c e  Second, ECS has b e e n assumed t o p r o d u c e a  i s produced  (Toman, S w i n y a r d , & Goodman, 1 9 4 6 ) .  The most i n f l u e n t i a l s t a t e m e n t o f t h e p a t t e r n e d t h a t o f Hebb ( 1 9 4 9 ) .  tially  as p a t t e r n s  and l a t e r neurons continue  1955;  o f n e u r a l f i r i n g p r o v i d i n g t h a t a " c o m p l e t e be-  havioral convulsion"  is  (Gerard,  firing  Hebb s u g g e s t e d t h a t memory was  held  of n e u r a l f i r i n g r e v e r b e r a t i n g i n c l o s e d  hypothesis initicircuits,  i n the f o r m o f a l t e r e d s t r u c t u r a l r e l a t i o n s b e t w e e n the  i n the c i r c u i t . until  The  r e v e r b e r a t i n g a c t i v i t y was  thought to  t h e permanent s t r u c t u r a l c h a n g e s c o n s t i t u t i n g t h e  p r y were formed and t o be n e c e s s a r y f o r t h e i r f o r m a t i o n . s o l i d a t i o n was  assumed t o i n v o l v e p a t t e r n s  Since  of n e u r a l f i r i n g ,  memcon-  any  t r e a t m e n t w h i c h p r o d u c e d a s e v e r e d i s r u p t i o n of n e u r a l f i r i n g w o u l d  be  e x p e c t e d t o p r o d u c e a c o m p l e t e d i s r u p t i o n of memories n o t y e t c o n s o l i d a t e d and s t i l l h e l d  i n the f o r m of r e v e r b e r a t i n g a c t i v i t y .  t h o s e memories a l r e a d y p e r m a n e n t l y s t o r e d w o u l d r e m a i n  intact.  ECS, p r o v i d i n g t h e c u r r e n t i n t e n s i t y i s s u f f i c i e n t l y t y p i c a l l y produces a p e r i o d of h i g h v o l t a g e  Only  strong,  synchronous s e i z u r e  dis-  c h a r g e w h i c h a p p e a r s t h r o u g h o u t t h e b r a i n and w h i c h i s f o l l o w e d by a p e r i o d of d e p r e s s i o n  of n e u r a l a c t i v i t y .  This massive  disturbance  of n e u r a l a c t i v i t y s h o u l d neural f i r i n g , solidation  d i s r u p t any o n g o i n g p a t t e r n s o f  and t h e r e f o r e p r o d u c e a c o m p l e t e c e s s a t i o n o f t h e c o n -  process.  lost, while  completely  The memories s t i l l h e l d i n t h i s f o r m s h o u l d  t h o s e w h i c h had a l r e a d y b e e n p e r m a n e n t l y s t o r e d  remain i n t a c t . involve only  t h i s one p h a s e , namely t h e t r a n s c r i b i n g o f p e r m a n e n t  t h e l e n g t h o f t h e ECS g r a d i e n t s h o u l d  time normally The  should  A c c o r d i n g l y , i f memory c o n s o l i d a t i o n i s assumed t o  memory f r o m a l a b i l e memory t r a c e c o n s i s t i n g o f p a t t e r n e d ing,  be  reflect  r e q u i r e d f o r c o n s o l i d a t i o n to reach  seizure discharge  neural  fir-  the d u r a t i o n of completion.  p r o d u c e d by ECS i s u s u a l l y a c c o m p a n i e d b y  an o v e r t b e h a v i o r a l c o n v u l s i o n i n w h i c h a l l t h e s k e l e t a l m u s c l e s c o n tract.  The c o n v u l s i o n p r o d u c e d b y a s u f f i c i e n t l y s t r o n g ECS i s h i g h l y  stereo-typed,  involving a brief  a tonic extension. b o d y , and h i n d l i m b  t o n i c f l e x i o n o f t h e body f o l l o w e d b y  The t o n i c e x t e n s i o n s p r e a d s c a u d a l l y a l o n g t h e t o n i c e x t e n s i o n has g e n e r a l l y been taken  cate a complete b e h a v i o r a l c o n v u l s i o n . f o l l o w e d by a p e r i o d of c l o n u s  to i n d i -  The t o n i c e x t e n s i o n p h a s e i s  and t h e p o s t i c t a l coma.  Toman e t a l .  (1946) o b s e r v e d t h a t t h e f o r m o f t h e t o n i c c o n v u l s i o n d i d n o t v a r y w i t h ECS p a r a m e t e r s , and c o n c l u d e d during a t o n i c extensor  that "the b r a i n i s maximally a c t i v e  s e i z u r e , and t h e d i s c h a r g e  independent of the s t i m u l u s "  once i n i t i a t e d i s  ( p . 2 3 8 ) . L a r g e l y on t h e b a s i s o f t h i s  c o n c l u s i o n t h e a p p e a r a n c e of a t o n i c b e h a v i o r a l c o n v u l s i o n has b e e n incorrectly  assumed t o r e f l e c t a m a x i m a l n e u r a l s e i z u r e .  Recently,  C h o r o v e r and DeLuca (1969) f o u n d t h a t ECS f o l l o w i n g a f o o t s h o c k c a n produce a t o n i c c o n v u l s i o n w i t h o u t  producing  c o r t i c a l seizure  discharge  18 L e n g t h o f ECS G r a d i e n t s The l e n g t h s o f ECS g r a d i e n t s have b e e n f o u n d t o v a r y g r e a t l y ; g r a d i e n t s h a v e b e e n o b t a i n e d w h i c h e x t e n d f o r 10 s e c o n d s S c h i l l e r , 1 9 6 5 ) , 20 s e c o n d s (Quartermain et a l . ,  ( P f i n g s t & K i n g , 1 9 6 9 ) , 60 s e c o n d s  1 9 6 5 ) , 1 hour  (McGaugh, 1 9 6 6 ) , and even 6 h o u r s R o b u s t e l l i , G e l l e r , and J a r v i k  ( H e r i o t & Coleman, 1962), 3 hours (Kopp e t a l . , 1 9 6 6 ) .  A c l a i m by  (1970) t o have d e m o n s t r a t e d  of 23 h o u r s i s i n v a l i d , s i n c e t h e i r dependent.  (Chorover &  a gradient  e f f e c t was n o t shown t o be t i m e -  The l o n g e s t g r a d i e n t d e m o n s t r a t e d w i t h a s i n g l e ECS i s 6  hours. A number o f v a r i a b l e s have b e e n f o u n d t o a f f e c t t h e l e n g t h of t h e ECS g r a d i e n t . apparatus  These i n c l u d e p r i o r  e x p e r i e n c e w i t h the t r a i n i n g  ( M i l l e r , 1970), the l e v e l of f o o t s h o c k used  (Ray & B i v e n s ,  1 9 6 8 ) , t h e n a t u r e of t h e t r a i n i n g p r o c e d u r e ( C h o r o v e r & S c h i l l e r , 1966; Thompson & P e n n i n g t o n , 1 9 5 7 ) , and even t h e t i m e o f day ( S t e p h e n s & McGaugh, 1 9 6 8 ) .  The e x p l a n a t i o n s f o r t h e e f f e c t s o f t h e s e  treat-  ments on t h e l e n g t h o f t h e ECS g r a d i e n t have n o t b e e n e s t a b l i s h e d . However, one p o s s i b i l i t y  i s t h a t the d u r a t i o n of time r e q u i r e d f o r  c o n s o l i d a t i o n i s not c o n s t a n t b u t v a r i e s w i t h both the n a t u r e of the memory and t h e s t a t e o f t h e a n i m a l . A n o t h e r v a r i a b l e w h i c h has been f o u n d t o a f f e c t t h e l e n g t h of the ECS g r a d i e n t  i s t h e n a t u r e o f t h e ECS t r e a t m e n t .  The d i s r u p t i v e  e f f e c t s of ECS have b e e n found t o v a r y d e p e n d i n g on t h e manner i n w h i c h ECS i s a d m i n i s t e r e d . Ray and B a r r e t t c r o s s t h e eyes  (1969) f o u n d t h a t ECS a-  ( v i a c o r n e a l e l e c t r o d e s ) d i s r u p t e d performance at  lower i n t e n s i t i e s  than c u r r e n t across  the ears.  Likewise, King  (1969)  found t h a t c u r r e n t p a s s e d b e t w e e n s c r e w e l e c t r o d e s o v e r t h e a n t e r i o r c o r t e x d i s r u p t e d performance a t lower i n t e n s i t i e s across  e l e c t r o d e s over the p o s t e r i o r c o r t e x .  t h e amount of i m p a i r m e n t was  than that r e q u i r e d  I n both these experiments,  f o u n d t o be more d e p e n d e n t on t h e mode  of d e l i v e r y t h a n on t h e f o r m of t h e b e h a v i o r a l c o n v u l s i o n , s i n c e t h e l o w e r i n t e n s i t i e s of ECS  d i d not produce  tonic convulsions.  I n a d d i t i o n t o t h e i m p o r t a n c e of t h e l o c u s of ECS  administration,  a number of e x p e r i m e n t s have f o u n d t h a t t h e l e n g t h of t h e ECS depends on the c u r r e n t p a r a m e t e r s , even when a l l p a r a m e t e r s tonic convulsions. to a f f e c t  the l e n g t h of t h e g r a d i e n t .  Miller  the l e n g t h of t h e g r a d i e n t f r o m 5 m i n u t e s  (1968) f o u n d  e x p e r i m e n t s i n v e s t i g a t i n g t h e e f f e c t of v a r y i n g ECS  & J a r v i k , 1968; Hughes, B a r r e t t , & Ray, Bush, M a r t i n , & Hunt, 1969). 1965; Weissman, 1963)  failed  1970;  M o s t of t h e intensity (Dorfman  L e e - T e n g , 1969;  Pagano,  (Quartermain et a l . ,  t o f i n d an e f f e c t of ECS  i n t e n s i t y o n l y i n c r e a s e s up  increased  intensities  However, two s t u d i e s  p o s s i b l e r e a s o n f o r t h e s e two n e g a t i v e  that i n -  t o 100 ma  t o 50 m i n u t e s .  have a l s o f o u n d g r e a t e r i m p a i r m e n t s w i t h h i g h e r  ECS  produce  B o t h c u r r e n t i n t e n s i t y and d u r a t i o n have b e e n f o u n d  c r e a s i n g t h e i n t e n s i t y o f t h e c u r r e n t f r o m 35 ma  ether  gradient  intensity.  A  f i n d i n g s i s t h a t the e f f e c t of  to an a s y m p t o t e .  T h i s has b e e n shown  by t h e two s t u d i e s w h i c h have s y s t e m a t i c a l l y examined t h e e f f e c t o f i n c r e a s i n g ECS  intensity  (Dorfman  & J a r v i k , 1968;  I n b o t h e x p e r i m e n t s , t h e amount o f d i s t u r b a n c e was  Lee-Teng, 1969). found to  increase  w i t h i n t e n s i t y up t o a p o i n t , beyond w h i c h f u r t h e r i n c r e a s e s i n  20 i n t e n s i t y d i d not produce g r e a t e r d i s t u r b a n c e s The c a n t as  e f f e c t of ECS  intensity.  d u r a t i o n has  Dorfman and  P a o l i n o , Q u a r t e r m a i n , and L e v y e f f e c t of v a r y i n g ECS Dorfman and  n o t b e e n f o u n d t o be  J a r v i k (1968), M i l l e r (1969) have a l l f a i l e d  duration.  (0.1 t o 3.0  s e c o n d d u r a t i o n ECS  seconds).  impaired  (1968),  On  to d e t e c t  ( u s i n g lower  somehow be  The  f i n d i n g s t h a t ECS  tied  to 3 h o u r s .  0.2 im-  treatment  is incorrect.  hypothesis  of p a t t e r n e d  i n t e n s i t y ECS  The  durations  duration  t o keep the  total  i n l e n g t h depending  a-  neural f i r i n g , expected  on  as a u n i t a r y  These f i n d i n g s a l s o do n o t s u p p o r t  a  simple  s i n c e the s e i z u r e produced to d i s r u p t s u c h a p r o c e s s  same d e g r e e as the s e i z u r e p r o d u c e d by a h i g h  i n t e n s i t y ECS.  t h e s e f i n d i n g s n e c e s s i t a t e a r e c o n s i d e r a t i o n of t h e  s h i p of the l e n g t h of ECS  Alpern  equal). gradients vary  w o u l d be  differ-  to the f a c t that  c u r r e n t p a r a m e t e r s c l e a r l y show t h a t t h e e a r l y v i e w of ECS  dation  studies,  They f o u n d t h a t a  v a r i e d b o t h i n t e n s i t y and  i n t e n s i t i e s with higher  of energy a p p r o x i m a t e l y  quently  any  the o t h e r h a n d , p o s i t i v e r e s u l t s  s e c o n d s ) p r o d u c e d g r a d i e n t s of up  McGaugh (1968) s i m u l t a n e o u s l y  a low  and  a f t e r p a s s i v e a v o i d a n c e t r a i n i n g , w h i l e l o n g e r d u r a t i o n ECSs  or 0.8  fliount  signifi-  p e r f o r m a n c e o n l y when a d m i n i s t e r e d  ence b e t w e e n t h e s e r e s u l t s may and  as  I n the most t h o r o u g h of t h e s e  have b e e n f o u n d by A l p e r n and McGaugh ( 1 9 6 8 ) .  (0.4  performance.  J a r v i k (1968) f o u n d no d i f f e r e n c e s o v e r a v e r y w i d e r a n g e  of d u r a t i o n s  mediately  of  to  by the  Conserelation-  g r a d i e n t s t o t h e d u r a t i o n of memory  consoli-  21 Two P o s s i b l e R e l a t i o n s h i p s B e t w e e n t h e L e n g t h o f ECS and  Gradients  t h e D u r a t i o n o f Memory C o n s o l i d a t i o n  T h e r e a r e two h y p o t h e s e s c o n c e r n i n g  the d u r a t i o n of c o n s o l i d a t i o n  w h i c h f o l l o w f r o m t h e f i n d i n g s o f v a r i a t i o n s i n ECS g r a d i e n t s w i t h r e n t parameters. completely  One p o s s i b i l i t y  i s t h a t memory c o n s o l i d a t i o n i s n o t  d i s r u p t e d b y e v e r y ECS, b u t o n l y by t h o s e o f s u f f i c i e n t l y  high i n t e n s i t y .  Lee-Teng (1969),  and D o r f m a n and J a r v i k (1968) b o t h  f o u n d t h a t i n c r e a s i n g ECS i n t e n s i t y o n l y i n c r e a s e d turbance flect dated.  cur-  o f p e r f o r m a n c e up t o an a s y m p t o t e .  t h e amount o f d i s -  This asymptote might r e -  t h e p o i n t a t w h i c h ECS d i s r u p t e d a l l t h e memory n o t y e t c o n s o l i I f this possibility  i s c o r r e c t , the l e n g t h of the amnesia  g r a d i e n t p r o d u c e d b y a h i g h i n t e n s i t y ECS w o u l d c o r r e s p o n d  to the  d u r a t i o n o f t i m e r e q u i r e d f o r t h e c o n s o l i d a t i o n of memory. The  other hypothesis  i s that c o n s o l i d a t i o n continues  -than t h e l e n g t h o f ECS g r a d i e n t s , e v e n t h o s e t e n s i t y ECS. convulsant  This  i s supported  b e e n f o u n d w i t h ECS ( G h e r k i n ,  1969).  a v o i d a n c e r e s p o n s e when a d m i n i s t e r e d This very  was o b t a i n e d asymptotic The  long g r a d i e n t  g r a d i e n t t h a n any w h i c h h a v e that  performance of a p a s s i v e  24 h o u r s b u t n o t 48 h o u r s  i s of p a r t i c u l a r  i n the same s i t u a t i o n i n w h i c h Lee-Teng  g r a d i e n t of a p p r o x i m a t e l y  that f l u r o t h y l , a  C h e r k i n , u s i n g c h i c k s , found  a high c o n c e n t r a t i o n of f l u r o t h y l impaired  training.  obtained with a high i n -  by a r e c e n t f i n d i n g  v a p o u r , p r o d u c e s a much l o n g e r  f o r longer  after  interest since i t (1970b) f o u n d a n  one m i n u t e u s i n g ECS.  a s y m p t o t e found w i t h ECS i n t e n s i t y  (Dorfman & J a r v i k , 1968;  Lee-Teng, 1969) i s n o t i n c o n s i s t e n t w i t h t h i s l a t t e r  hypothesis.  Instead  of r e f l e c t i n g a c o m p l e t e d i s t u r b a n c e  of c o n s o l i d a t i o n , the  a s y m p t o t e may r e f l e c t some c h a r a c t e r i s t i c o f t h e s e i z u r e p r o d u c e d by ECS.  There i s evidence i n d i c a t i n g  that several aspects  of the s e i z u r e  p r o d u c e d by ECS i n c r e a s e w i t h ECS i n t e n s i t y up t o a c e r t a i n l e v e l b u t beyond t h i s l e v e l f u r t h e r i n c r e a s e s i n ECS i n t e n s i t y do n o t p r o d u c e increments i n the s e i z u r e .  F o r e x a m p l e , M i n z and Domino (1953) f o u n d  t h a t the d u r a t i o n of c o r t i c a l s e i z u r e d i s c h a r g e  p r o d u c e d b y ECS i n  s p i n a l c a t s i n c r e a s e d w i t h ECS i n t e n s i t y up t o a p o i n t b e y o n d w h i c h f u r t h e r i n c r e a s e s i n i n t e n s i t y d i d not r e s u l t i n l o n g e r d u r a t i o n s of discharge. discharge  Zornetzer  and McGaugh (1970) r e c e n t l y examined t h e s e i z u r e  p r o d u c e d by ECS i n r a t s .  Contrary  t o M i n z and Domino  they found t h a t the d u r a t i o n of s e i z u r e d i s c h a r g e with intensity. and  continued  The r e a s o n f o r t h i s d i f f e r e n c e i s u n c l e a r .  (1953),  to increase Zornetzer  McGaugh d i d , h o w e v e r , r e p o r t t h a t t h e f r e q u e n c y o f t h e s e i z u r e  discharge  o n l y i n c r e a s e d up t o a p o i n t .  W h i l e more r e s e a r c h needs t o  be done o n t h e r e l a t i o n s h i p o f s e i z u r e d i s c h a r g e  t o ECS  intensity,  t h e s e f i n d i n g s i n d i c a t e t h a t some a s p e c t s  of t h e s e i z u r e produced by  ECS may n o t c o n t i n u e  intensity.  t o i n c r e a s e w i t h ECS  On t h e b a s i s o f t h e a v a i l a b l e e v i d e n c e ,  i t i s not p o s s i b l e to  d e c i d e w i t h c e r t a i n t y w h e t h e r t h e a s y m p t o t e f o u n d w i t h ECS r e f l e c t s a maximal d i s t u r b a n c e of u n c o n s o l i d a t e d  intensity  memory, o r w h e t h e r i t  r e f l e c t s a f a i l u r e of t h e n e u r o n a l  disturbance  p r o d u c e d by ECS t o c o n -  t i n u e to i n c r e a s e w i t h i n t e n s i t y .  A p o s s i b l e way o f c l a r i f y i n g  i s s u e m i g h t be t o examine w h e t h e r i n c r e a s i n g t h e n e u r o n a l p r o d u c e d by ECS w i l l  result  i n further increases  this  disturbance  i n t h e amount o f  23 impairment.  A s e r i e s of ECSs, each of w h i c h produces a s e p a r a t e  s e i z u r e , s h o u l d p r o d u c e a g r e a t e r d i s t u r b a n c e t h a n a s i n g l e ECS.  M u l t i p l e ECSs S e v e r a l e a r l y experiments have observed time-dependent  impair-  ments u s i n g m u l t i p l e ECSs w h i c h w e r e o f g r e a t e r d u r a t i o n t h a n any r e p o r t e d w i t h a s i n g l e ECS.  Hunt and B r a d y  (1951) and B r a d y  (1952) f o u n d  t h a t a s e r i e s of 21 ECSs p r e s e n t e d t h r e e t i m e s p e r day i m p a i r e d t h e p e r f o r m a n c e o f a CER a c q u i r e d  through e i g h t t r i a l s  spaced over a 31-  day p e r i o d , i f t h e t r e a t m e n t s w e r e s t a r t e d 1 o r 2 d a y s a f t e r training  trial.  the l a s t  However, t h e e f f e c t o f t h e ECSs was m a r k e d l y  if  t h e ECSs w e r e d e l a y e d 30 d a y s , and o n l y s l i g h t i m p a i r m e n t  if  t h e d e l a y was 90 d a y s .  Williams  ( 1 9 6 1 , 1963) g a v e e i g h t  reduced appeared  daily  t r a i n i n g t r i a l s on a c o n f l i c t t r a i n i n g p r o c e d u r e , i n w h i c h r a t s w e r e trained  to cross an e l e c t r i f i e d  grid  to o b t a i n water.  A s e r i e s of  e i g h t d a i l y ECSs w e r e f o u n d t o e l i m i n a t e g r i d h e s i t a t i o n , of  c o n f l i c t , when s t a r t e d  ing  1 day b u t n o t 13 d a y s a f t e r  t h e measure  the l a s t  train-  trial. In  b o t h t h e s e s e t s of e x p e r i m e n t s , t h e t r a i n i n g p r o c e d u r e  many t r i a l s s p a c e d o v e r a p e r i o d o f d a y s , c r e a t i n g d i f f i c u l t y  involved  f o r com-  p a r i n g t h e s e f i n d i n g s t o t h o s e o b t a i n e d w i t h a s i n g l e ECS f o l l o w i n g trial  learning.  one  N e v e r t h e l e s s , these impairments a r e not g e n e r a l l y i n -  t e r p r e t e d as e x t e n s i o n s o f t h e s o r t o f d e f i c i t p r o d u c e d by a s i n g l e ECS  ( H u n t , 1965; McGaugh, 1 9 6 8 ) , b u t r a t h e r a r e u s u a l l y  on the b a s i s o f s e v e r a l s u p p o s e d l y a p p a r e n t e m p i r i c a l  distinguished  differences.  T h e r e a r e t h r e e ways i n w h i c h t h e d e f i c i t s p r o d u c e d by s i n g l e m u l t i p l e ECSs have b e e n t h o u g h t t o d i f f e r .  First,  the impairment p r o -  duced by m u l t i p l e ECS h a s b e e n r e p o r t e d t o be o n l y t e m p o r a r y 1 9 5 1 ) , n o t a p p e a r i n g i f t e s t i n g was ECSs i n s t e a d o f t h e u s u a l 4 d a y s . d e f i c i t s p r o d u c e d by a s i n g l e ECS 1965; L u t t g e s & McGaugh, 1 9 6 7 ) .  g i v e n 30 days a f t e r On  a r e u s u a l l y permanent  M i l l e r , & M i s a n i n , 1968). (1961) was  (Chevalier,  1969)  a l s o reappear spontaneously  or f o l l o w i n g a " r e m i n d e r " ( L e w i s , t h e d e f i c i t o b s e r v e d by  Williams  a p p a r e n t l y permanent f o r a t l e a s t 52 d a y s .  not to d i s t u r b other responses. p o r t e d t h a t m u l t i p l e ECS  thought to s e l e c t i v e l y  i . e . the CER was  acquired response. a s i n g l e ECS may of r e s p o n s e s .  i m p a i r a CER  G e l l e r , S i d m a n , and B r a d y  i m p a i r e d a CER,  and  (1955) r e -  but not a bar p r e s s response  f o r w a t e r even though t h e b a r p r e s s r e s p o n s e was  produced  performance  However, s e v e r a l s t u d i e s h a v e shown  Moreover,  S e c o n d , m u l t i p l e ECS was  CER,  (Brady,  the s e r i e s of  t h e o t h e r h a n d , the  t h a t r e s p o n s e s d i s t u r b e d by a s i n g l e ECS may o v e r t i m e ( e . g . , Pagano e t a l . ,  and  acquired after  s e l e c t i v e l y d i s t u r b e d , not j u s t  the most  the recently  However, t h e r e i s a l s o some e v i d e n c e s h o w i n g  that  b e more e f f e c t i v e i n d i s t u r b i n g CERs t h a n o t h e r s o r t s  C h o r o v e r and S c h i l l e r  l o n g e r g r a d i e n t s i n a CER  (1966) f o u n d t h a t a s i n g l e  ECS  t a s k t h a n i n two o t h e r v a r i a n t s o f  passive avoidance t r a i n i n g procedures. The  t h i r d a p p a r e n t d i f f e r e n c e b e t w e e n t h e e f f e c t s of s i n g l e  m u l t i p l e ECS  and  i s the r e p o r t e d requirement of the o v e r t c o n v u l s i o n f o r  the d i s t u r b a n c e p r o d u c e d by m u l t i p l e b u t n o t by s i n g l e ECS.  Hunt,  J e r n b e r g , and L a w l o r (1953) f o u n d t h a t t h e s e r i e s of 21 ECSs d i d n o t  p r o d u c e i m p a i r m e n t of a CER  i f they were p r e s e n t e d  were a n e s t h e t i z e d w i t h e t h e r . presenting blocked  H u n t and  Beckwith  the ECSs u n d e r phenacemide b u t  the e f f e c t of ECS.  while  the  (1955) f o u n d  B o t h e t h e r and  still  which blocked  the o v e r t c o n v u l s i o n .  Essman (1968) u s i n g l i d o c a i n e and and  was  g i v e n under ether  The  prevented  same r e s u l t was  The  t o d i f f e r q u a l i t a t i v e l y on  ECS  anesthesia obtained  2, 4, d i c h l o r o p h e n o x y a c e t i c  by  acid,  and  phena-  s i n g l e and m u l t i p l e ECSs do n o t  appear  the o v e r t  g r a d i e n t s p r o d u c e d by  McGaugh  a single  Weissman (1965) u s i n g p h e n o b a r b i t a l , d i p h e n y l h y d a n t o i n ,  c e m i d e , a l l of w h i c h b l o c k e d  the  seizure.  (1966) showed t h a t the i m p a i r m e n t p r o d u c e d by  a p p e a r e d e v e n t h o u g h t h e ECS  also  phenacemide prevented  t h e a p p e a r a n c e of a t o n i c e x t e n s i o n b u t n o t a r u n n i n g Alpern  that  not d i p h e n y l h y d a n t o i n  a p p e a r a n c e of o v e r t c o n v u l s i o n s , w h i l e d i p h e n y l h y d a n t o i n  and  animals  convulsion.  the b a s i s of e i t h e r t h e permanence of  e f f e c t o r the s e l e c t i v e d i s t u r b a n c e  o f CERs.  On  the o t h e r hand,  a p p a r e n t d i f f e r e n t i a l r e q u i r e m e n t of t h e c o n v u l s i o n does p r o v i d e  the the sup-  p o r t f o r t h e p o s s i b i l i t y t h a t t h e g r a d i e n t s p r o d u c e d by s i n g l e and m u l t i p l e ECSs r e f l e c t d i f f e r e n t p r o c e s s e s . of t h i s  However, c l o s e r  examination  l a t t e r d i f f e r e n c e reveals several f a c t o r s which create  c u l t i e s f o r drawing a f i r m d i s t i n c t i o n . d i f f e r e n t e x p e r i m e n t s and treatments  First,  i t i s i m p o s s i b l e t o be  ( a n t i c o n v u l s a n t d r u g d o s e s and  ECS  these data  c e r t a i n that  S t i l l e and  was  not b l o c k e d  from the  l e v e l s ) were c o m p a r a b l e .  T h i s i s a problem because i t i s p o s s i b l e t h a t the s e i z u r e p r o d u c e d by ECS  are  diffi-  discharge  even though the o v e r t c o n v u l s i o n  S a y e r s (1967) examined a number o f d r u g s w h i c h b l o c k e d  was. the  26 overt convulsion  ( i n c l u d i n g phenacemide, d i p h e n y l h y d a n t o i n ,  and pheno-  b a r b i t a l ) and f o u n d t h a t t h e c o r t i c a l s e i z u r e d i s c h a r g e was u n a f f e c t e d by  the drugs.  The d i f f e r e n t i a l e f f e c t s o b s e r v e d b e t w e e n s i n g l e and  m u l t i p l e ECS when t h e c o n v u l s i o n was b l o c k e d , may r e f l e c t  the s e i z u r e  being blocked  experiments,  i n t h e m u l t i p l e , b u t n o t i n t h e s i n g l e ECS  whether o r n o t t h e s e i z u r e s w e r e b l o c k e d  probably  depends on a n i n t e r -  a c t i o n b e t w e e n t h e amount o f d r u g and ECS p a r a m e t e r s , and i s d i f f i c u l t to e v a l u a t e  i n the absence of r e c o r d i n g s .  periments f i n d i n g  long gradients  w i t h m u l t i p l e ECS t r e a t m e n t s  t r a i n i n g p r o c e d u r e s i n v o l v i n g many t r i a l s creating d i f f i c u l t y  Second, b o t h s e t s of exused  spaced over a p e r i o d of days,  f o r comparing these f i n d i n g s to those  obtained  w i t h a s i n g l e ECS f o l l o w i n g o n e - t r i a l l e a r n i n g .  Summary and R a t i o n a l e o f t h e P r e s e n t I n v e s t i g a t i o n The  e a r l y v i e w t h a t t h e l e n g t h o f t h e ECS g r a d i e n t  t o t h e d u r a t i o n o f c o n s o l i d a t i o n i s no l o n g e r  tenable.  corresponded The l e n g t h o f  t h e g r a d i e n t p r o d u c e d by ECS has b e e n f o u n d t o v a r y w i t h ECS p a r a m e t e r s . S i n c e t h e l e n g t h o f t h e ECS g r a d i e n t i s n o t c o n s t a n t , i n g f u l to i d e n t i f y  i t i s n o t mean-  t h e d u r a t i o n o f c o n s o l i d a t i o n as t h e l e n g t h o f t h e  gradient obtained with  a n a r b i t r a r y ECS.  T h e r e r e m a i n two p o s s i b i l i -  t i e s f o r t h e r e l a t i o n of t h e l e n g t h o f t h e ECS g r a d i e n t of c o n s o l i d a t i o n . tion  One p o s s i b i l i t y  to the d u r a t i o n  i s that the d u r a t i o n of c o n s o l i d a -  c o r r e s p o n d s n o t t o t h e l e n g t h o f any a r b i t r a r y ECS g r a d i e n t ,  but o n l y t o those second p o s s i b i l i t y  obtained  w i t h an ECS o f s u f f i c i e n t i n t e n s i t y ,  i s t h a t memory c o n s o l i d a t i o n c o n t i n u e s  The  f o r longer  27 than the length of even a high i n t e n s i t y ECS  gradient.  Support f o r the f i r s t p o s s i b i l i t y comes p r i m a r i l y from the i n g that ECS level.  The  i n t e n s i t y only increases the ECS  asymptotic  l a t t e r p o s s i b i l i t y r e q u i r e s that t h i s asymptote r e f l e c t s  the l i m i t e d neuronal producing.  gradient to an  find-  disturbance which a s i n g l e ECS  There i s evidence  discharge produced by ECS  i s capable  that a l l e a s t some aspects  of  of the s e i z u r e  reach an asymptote with i n c r e a s i n g ECS  intensity. T e n t a t i v e support  f o r the second p o s s i b i l i t y i s provided  s e v e r a l e a r l y s t u d i e s (Brady, 1952;  W i l l i a m s , 1963)  by  which have found  gradients of much greater length than those obtained with a s i n g l e ECS.  However, inferences from these s t u d i e s are complicated  p o s s i b i l i t y that these longer gradients may cess than s i n g l e ECS  gradients.  by  the  reflect a different  This p o s s i b i l i t y i s suggested  m a r i l y by the apparent d i f f e r e n t i a l e f f e c t s found when the  propri-  convulsion  was.blocked. The purpose of the present i n v e s t i g a t i o n i s to determine whether a s e r i e s of ECSs can produce gradients which do not r e f l e c t a q u a l i t a t i v e l y d i f f e r e n t process  than gradients produced by a s i n g l e ECS,  but  which are of greater length.  I f such gradients can be obtained,  should provide strong support  f o r the p o s s i b i l i t y that memory c o n s o l i -  d a t i o n continues Two  f o r longer than the length of s i n g l e ECS  they  gradients.  p o s s i b l e ways of i n v e s t i g a t i n g the e f f e c t s of a s e r i e s of ECSs  are to vary the number of ECSs or to keep the number constant but the spacings between them.  This l a t t e r approach was  vary  used by Brady,  H u n t , and G e l l e r ( 1 9 5 4 ) .  They f o u n d t h a t a s e r i e s o f 21 ECSs p r o d u c e d  s u b s t a n t i a l i m p a i r m e n t o f a CER when s p a c e d 1, 8, o r 24 h o u r s  apart.  However, when t h e 21 ECSs w e r e s p a c e d 30 m i n u t e s a p a r t , l e s s i m p a i r ment of t h e CER was f o u n d and when s p a c e d 1 s e c o n d a p a r t no i m p a i r ment was o b s e r v e d .  The a d v a n t a g e o f t h i s l a t t e r a p p r o a c h i s t h a t t h e  e f f e c t o f a s e r i e s o f ECSs c a n be examined w i t h o u t of c u r r e n t a d m i n i s t e r e d  to the animals  v a r y i n g t h e amount  i n the v a r i o u s c o n d i t i o n s .  In  a d d i t i o n , t h i s l a t t e r a p p r o a c h a p p e a r s t o be b e t t e r s u i t e d f o r t h e purpose of the p r e s e n t ECSs s p a c e d c l o s e l y  i n v e s t i g a t i o n , s i n c e by p r e s e n t i n g a s e r i e s o f  together  an e f f e c t o n l y s l i g h t l y g r e a t e r  p r o d u c e d by a s i n g l e ECS may be o b t a i n e d . ually  As the s p a c i n g s  than  that  are grad-  i n c r e a s e d , t h e e f f e c t of t h e ECS may a l s o g r a d u a l l y i n c r e a s e .  The o b t a i n e d  r e s u l t s may  t h e r e f o r e be c o m p a r a b l e t o t h o s e  obtained  w i t h a s i n g l e ECS e x c e p t g r e a t e r i n m a g n i t u d e . The p r e s e n t  experiments are d i v i d e d i n t o three p a r t s .  The  first  e x p e r i m e n t i n v e s t i g a t e d t h e e f f e c t o f a s e r i e s o f ECSs o n p e r f o r m a n c e of a p a s s i v e a v o i d a n c e r e s p o n s e a c q u i r e d  i n a single trial.  The  pur-  p o s e o f t h i s e x p e r i m e n t was t o d e t e r m i n e w h e t h e r t h e l e n g t h o f t h e g r a d i e n t c o u l d be i n c r e a s e d as t h e s p a c i n g s  b e t w e e n t h e ECSs w e r e i n -  creased . Since  the f i r s t  e x p e r i m e n t showed t h a t a l o n g e r g r a d i e n t  p r o d u c e d by a s e r i e s o f s p a c e d ECSs, a s e c o n d e x p e r i m e n t was to  d e t e r m i n e w h e t h e r t h i s l o n g e r g r a d i e n t w o u l d be a t t e n u a t e d  r e s u l t of b l o c k i n g the b e h a v i o r a l c o n v u l s i o n . included  to evaluate  the p o s s i b i l i t y  was  conducted as a  T h i s e x p e r i m e n t was  t h a t t h e s e r i e s o f ECSs p r o d u c e d  29 a q u a l i t a t i v e l y d i f f e r e n t e f f e c t than a s i n g l e A f i n a l e x p e r i m e n t was  included  ECS.  to determine whether  the s e r i e s  of ECSs w o u l d a l s o p r o d u c e a p r o l o n g e d g r a d i e n t f o r an a p p e t i t i v e r e sponse a c q u i r e d i n a s i n g l e  trial.  EXPERIMENT 1: ON  The  THE  EFFECT OF A SERIES OF  ECSS  RETENTION OF A PASSIVE AVOIDANCE RESPONSE  p u r p o s e of t h i s f i r s t  e x p e r i m e n t was  to a s c e r t a i n whether  a s e r i e s of ECSs w o u l d p r o d u c e a t i m e - d e p e n d e n t i m p a i r m e n t of  per-  f o r m a n c e w h i c h i s of g r e a t e r m a g n i t u d e t h a n t h o s e p r o d u c e d by a ECS.  I n order  t o do  t h i s , 5 ECSs w e r e p r e s e n t e d ,  a p a r t or spaced 1 minute a p a r t . was  s p a c e d 5 seconds,  p e r f o r m a n c e of t h e s e  two  groups  compared w i t h t h a t of a g r o u p w h i c h r e c e i v e d o n l y one  ECS  but  f i v e times  the d u r a t i o n .  The  singl  T h i s group served  as a c o n t r o l f o r any  s i b l e e f f e c t of the amount of c u r r e n t p e r s e . t a s k was  of  A passive  pos-  avoidance  u s e d s i n c e t h i s i s the t y p e of l e a r n i n g p r o c e d u r e i n w h i c h  the e f f e c t s of a s i n g l e ECS  have b e e n most t h o r o u g h l y  documented.  Method Sub j e c t s N a i v e , m a l e , h o o d e d , 200-300 gm Breeding  Farm (now  Canadian Breeding  r a t s obtained  f r o m Quebec  L a b o r a t o r i e s ) served  as  subjects  Surgery The was  placed  animal  ( u n d e r sodium p e n t o b a r b i t a l a n e s t h e s i a , 45 mg/kg)  i n a s t e r e o t a x i c head h o l d e r and  s m a l l h o l e s were d r i l l e d  bilaterally  screw e l e c t r o d e s  diamter).  erior  (0.8 mm  to the bregma and  4 mm  lateral  i t s s k u l l exposed.  to r e c e i v e the  stainless-steel  These w e r e p o s i t i o n e d 1 mm to the s a g i t t a l  These s c r e w e l e c t r o d e s , a t t a c h e d  v i a connecting  Two  post-  suture. wires  to p i n s ,  p e n e t r a t e d j u s t t h r o u g h t h e s k u l l and w e r e i n c o n t a c t w i t h t h e d u r a l surface.  Two o t h e r s c r e w s w e r e p l a c e d i n t h e s k u l l  d i t i o n a l support.  to p r o v i d e ad-  A f t e r t h e s u p p o r t i n g and e l e c t r o d e s c r e w s w e r e i n  p l a c e , t h e s k u l l was w i p e d d r y and d e n t a l a c r y l i c cement was  applied  to c o v e r t h e s c r e w s and t h e wound a r e a i n s u c h a way t h a t o n l y t h e pins protruded.  Immediately f o l l o w i n g s u r g e r y , the a n i m a l s were  i n j e c t e d i n t r a p e r i t o n e a l l y w i t h 40 mg/kg p e n t y l e n e t e t r a z o l and m u s c u l a r l y w i t h 0.2 c c sodium p e n i c i l l i n  (Crysticillin).  intra-  Penicillin  was a l s o r o u t i n e l y g i v e n on t h e d a y f o l l o w i n g s u r g e r y and on t h e second f r o m l a s t p r e t r a i n i n g d a y . Apparatus The t r a i n i n g a p p a r a t u s was a g r a y p l y w o o d cm w i d e , and 20 cm h i g h .  alley  122 cm l o n g , 11  A s t a i n l e s s s t e e l d r i n k i n g spout s i m i l a r to  t h o s e u s e d i n t h e home c a g e s , b u t c o v e r e d w i t h m a s k i n g  tape except  for  A  t h e t i p , p r o t r u d e d f o r 2 cm t h r o u g h one end w a l l .  Physiological  E l e c t r o n i c s I n c . d r i n k o m e t e r was c o n n e c t e d t o t h e w a t e r s p o u t and t h e grid  f l o o r below the spout.  The t a p e on t h e d r i n k i n g s p o u t was t o  prevent the drinkometer from being a c t i v a t e d The g r i d f l o o r c o n s i s t e d o f 3 mm  except through the t i p .  d i a m e t e r b r a s s r o d s s p a c e d 13  mm a p a r t and w h i c h e x t e n d e d f o r 18 cm, t h e l a s t r o d b e i n g j o i n e d t o the h a r d w a r e c l o t h w h i c h c o m p r i s e d t h e f l o o r o f t h e r e s t o f t h e a l l e y . The g r i d f l o o r was c o n n e c t e d t o a c o n s t a n t c u r r e n t shock s o u r c e w h i c h c o u l d d e l i v e r 2.0 ma, AC f o o t s h o c k . ECS was a 60 Hz s i n e wave f r o m a n 840 v o l t w i t h a 44,000 ohm r e s i s t a n c e .  transformer i n series  ECS was d e l i v e r e d f r o m t h e t r a n s f o r m e r  via  f l e x i b l e w i r e s t e r m i n a t i n g i n b u t t e r f l y c l i p s w h i c h c o u l d be a t -  t a c h e d t o t h e p i n e x t e n s i o n s o f t h e screw, e l e c t r o d e s . In  o r d e r t o d e t e r m i n e t h e ECS c u r r e n t i n t e n s i t y , a s w e l l a s t h e  impedance imals  between  t h e c o r t i c a l s c r e w e l e c t r o d e s , i n a number o f a n -  t h e v o l t a g e d r o p a c r o s s e i t h e r t h e 44,000 ohm r e s i s t a n c e o r t h e  s c r e w e l e c t r o d e s was measured Oscilloscope. v a r y between 18.4  The impedance  d u r i n g ECS w i t h a T e k t r o n i c s 565 S t o r a g e between  t h e s c r e w e l e c t r o d e s was f o u n d t o  1,500 and 3,000 ohms, and t h e c u r r e n t b e t w e e n  17.9 and  milliamps.  T r a i n i n g Procedure The  a n i m a l s w e r e housed  i n g r o u p c a g e s and m a i n t a i n e d on f r e e l y  a v a i l a b l e w a t e r and P u r i n a f o o d chunks f o r a t l e a s t a week b e f o r e surgery.  F o l l o w i n g s u r g e r y , t h e a n i m a l s w e r e housed  individually.  Food c o n t i n u e d t o be f r e e l y a v a i l a b l e t h r o u g h o u t t h e e x p e r i m e n t , b u t crn  t h e s e c o n d day a f t e r s u r g e r y , t h e w a t e r b o t t l e s w e r e removed and  23-hour w a t e r d e p r i v a t i o n was m a i n t a i n e d f o r t h e r e s t o f t h e e x p e r i ment.  The a n i m a l s w e r e b r i e f l y h a n d l e d on t h e two days  surgery.  following  On t h e t h i r d d a y a f t e r s u r g e r y , e a c h a n i m a l , 21 t o 23 h o u r s  w a t e r d e p r i v e d , was p l a c e d i n t h e a p p a r a t u s f o r 10 m i n u t e s .  Animals  w e r e a l w a y s p l a c e d a t t h e end o p p o s i t e t h e d r i n k i n g s p o u t , f a c i n g t h e spout.  One h o u r a c c e s s t o w a t e r was g i v e n i n t h e home cages  each p r e t r a i n i n g s e s s i o n . in  On t h e f o u r t h d a y , t h e a n i m a l s w e r e p l a c e d  t h e a p p a r a t u s f o r 5 m i n u t e s and o n t h e f i f t h  first  d a y , f o r two p e r i o d s ,  f o r 3 m i n u t e s and t h e n , 1-2 h o u r s l a t e r , f o r 2 m i n u t e s .  s i x t h and s e v e n t h d a y s  following  On t h e  ( t h e l a s t two p r e t r a i n i n g d a y s ) t h e a n i m a l s  were given 3 t r i a l s , each of 1 minute d u r a t i o n , separated by 30-45 minutes.  This p r e t r a i n i n g procedure was used because p r e l i m i n a r y exper-  iments showed i t to be an e f f i c i e n t way of e s t a b l i s h i n g a strong d r i n k i n g response. On the l a s t two days of p r e t r a i n i n g , the d r i n k i n g latency was recorded with a stopwatch.  Animals not d r i n k i n g during each 1 minute  t r i a l were assigned a score of 60 seconds.  Those with mean l a t e n c i e s  over the three t r i a l s on the l a s t p r e t r a i n i n g day of greater than 23 seconds were d i s c a r d e d .  Approximately 10 percent of the animals were  excluded f o r t h i s reason. On the passive avoidance t r a i n i n g day (eighth day f o l l o w i n g surgery), the animals were placed on a stand beside the apparatus and wires f o r administering the ECS were attached.  A f t e r 1 minute of a-  daptation to the wires, a l l animals were given a s i n g l e t r i a l .  Upon  touching the spout the animals received one of s e v e r a l treatments depending on the experimental c o n d i t i o n . Experimental Conditions T h i s experiment involved a number of stages which were run seq u e n t i a l l y but which w i l l be presented together f o r s i m p l i c i t y .  Ani-  mals were g e n e r a l l y run i n l o t s of 30, with each l o t containing a n i mals i n 3 to 5 d i f f e r e n t treatment c o n d i t i o n s .  In order to minimize  d i f f e r e n c e s between treatment groups due to v a r i a t i o n i n l o t s of animals, the animals were assigned to groups on the b a s i s of t h e i r p r e t r a i n i n g l a t e n c i e s and a l l treatment 'groups were equated on t h i s measure.  There were g e n e r a l l y between 5 and 7 animals per treatment  34 group  ( s e e T a b l e 1 f o r t h e e x a c t number of a n i m a l s i n e a c h g r o u p ) . The a n i m a l s r e c e i v i n g p a s s i v e a v o i d a n c e t r a i n i n g w e r e a l l  a 1.0 s e c o n d , 2.0 ma f o o t s h o c k upon t o u c h i n g t h e s p o u t .  given  I n the im-  m e d i a t e ECS c o n d i t i o n , ECS o n s e t c o i n c i d e d w i t h t h e o f f s e t o f t h e f o o t s h o c k and was a d m i n i s t e r e d i n t h e a l l e y .  D e l a y e d ECS g r o u p s w e r e  r e t u r n e d t o t h e i r home c a g e s f o l l o w i n g t h e f o o t s h o c k and were  later  g i v e n ECS on t h e f e e d i n g s t a n d b e s i d e b e s i d e t h e a l l e y . W i t h i n t h i s f r a m e w o r k , t h e e f f e c t s o f t h r e e ECS t r e a t m e n t s w e r e examined.  T h e s e w e r e f i v e ECSs each o f 0.5 s e c o n d s d u r a t i o n s p a c e d 5  s e c o n d s a p a r t , f i v e ECSs o f 0.5 s e c o n d s d u r a t i o n s p a c e d 1 m i n u t e a p a r t , and one ECS o f 2.5 s e c o n d s d u r a t i o n . presented  i n T a b l e 1.  The t r e a t m e n t c o n d i t i o n s a r e  The o r i g i n a l d e s i g n i n c l u d e d o n l y t h e i m m e d i a t e ,  1 h o u r and 24 h o u r ECS d e l a y s .  When i t became a p p a r e n t t h a t t h e f i v e  ECSs s p a c e d 1 m i n u t e a p a r t i m p a i r e d p e r f o r m a n c e e v e n when p r e s e n t e d 24 h o u r s a f t e r t r a i n i n g , a d d i t i o n a l g r o u p s w e r e added t o e v a l u a t e w h e t h e r t h i s i m p a i r m e n t was t i m e - d e p e n d e n t . I n a d d i t i o n t o t h e s e e x p e r i m e n t a l g r o u p s , a number o f c o n t r o l c o n d i t i o n s were i n c l u d e d .  First,  to confirm that the d r i n k i n g r e -  s p o n s e e s t a b l i s h e d d u r i n g p r e t r a i n i n g was s t a b l e o v e r t h e d u r a t i o n o f the e x p e r i m e n t , two g r o u p s o f a n i m a l s w e r e g i v e n n e i t h e r  footshock  n o r ECS on t h e t r a i n i n g d a y , b u t w e r e s i m p l y removed f r o m t h e a p p a r a t u s upon t o u c h i n g t h e w a t e r s p o u t . after  One group was t e s t e d 48 h o u r s  t h e t r a i n i n g s e s s i o n and t h e o t h e r was t e s t e d a t 11 d a y s .  To  show t h a t t h e p a s s i v e a v o i d a n c e r e s p o n s e was a l s o s t a b l e , two o t h e r g r o u p s of r a t s w e r e g i v e n a f o o t s h o c k on t h e t r a i n i n g d a y , b u t no ECS.  35  Table 1  The Number of Subjects In Each Treatment C o n d i t i o n i n Experiment 1  Treatment  Time o f Testing  a  No FS  b  FS Only Immed.  FS-ECS Delay 1 hr. 24 h r . 48 h r . 9 days  No ECS  48 h r s .  N=5  N=10  -  -  -  -  -  No ECS  11 days  N=7  N=10  -  -  -  -  -  48 h r s .  N=5  -  N=5  N=7  N=6  48 h r s .  N=5  -  N=5  N=7  N=8  48 h r s .  N=5  -  N=8  N=7  N=7  11 days  -  N=6  N=5  1 ECS, 2.5 sec. duration  -  N=7  N=ll  N=8  5 ECS, 5 sec. apart 5 ECS, 1 min. apart 5 ECS, 1 min. apart  a  F o l l o w i n g ECS, or t r a i n i n g  b  F S = footshock  ( i n the no ECS conditions)  (passive avoidance t r a i n i n g )  These animals were tested either 48 hours or 11 days l a t e r . Several other control conditions were included to evaluate a l ternatives to the interpretation that the ECS treatments were producing a disturbance of memory consolidation.  F i r s t , three groups  were included to determine whether any aversive effects of the ECS treatments were s u f f i c i e n t l y strong to affect the drinking response. These received one of the three ECS treatments instead of footshock upon touching the water spout.  Second, to examine whether the impair  ments produced by the f i v e ECSs spaced 1 minute apart were permanent, two groups were given this treatment at 1 hour or 24 hours after training and tested 11 days following training. Animals i n a l l conditions received 1 hour access to water i n their home cages on each day of the experiment.  On days when ECS was  administered, water was given s t a r t i n g 1 hour after ECS. I f the animal received only t r a i n i n g , water was given 1 hour after training. A l l animals were approximately 23 hours water deprived during testing Retention tests were given either 48 hours after ECS, 48 hours after t r a i n i n g , or 11 days after t r a i n i n g , depending on the experimental condition (Table 1). Testing f o r a l l groups took the form of three t r i a l s , 30-45 minutes apart, i d e n t i c a l to those on the l a s t pretraining days.  Animals f a i l i n g to drink during the 60 second test  were removed and assigned a score of 60 seconds f o r that t r i a l .  The  latencies of the drinking response on each of the three t r i a l s on the test day were averaged f o r each animal. A l l s t a t i s i c a l analyses were performed on the mean drinking  37 latency  f o r each animal on the t e s t day.  These mean l a t e n c i e s d i d not  s a t i s f y the requirements f o r parametric a n a l y s i s , since score of 60 was obtained by a number of animals. Halperin's  the maximum  Consequently,  (1960) extension of the Mann-Whitney t e s t to samples cen-  sored a t the same f i x e d point was used. Results The  drinking  l a t e n c i e s f o r the c o n t r o l groups not r e c e i v i n g ECS  are presented i n Table 2. ance t r a i n i n g , the d r i n k i n g the  I n the groups not r e c e i v i n g passive avoidl a t e n c i e s of animals tested  48 hours a f t e r  t r a i n i n g day d i d not d i f f e r from those of animals not tested  11 days a f t e r the t r a i n i n g day.  These groups were therefore  With passive avoidance t r a i n i n g the s i t u a t i o n was s i m i l a r .  until  combined. The d r i n k -  ing l a t e n c i e s of the groups r e c e i v i n g passive avoidance t r a i n i n g (footshock) d i d not d i f f e r between the 48 hour and 11 day t e s t i n g s . At both times of t e s t i n g the l a t e n c i e s were s i g n i f i c a n t l y longer than the l a t e n c i e s of the corresponding groups not r e c e i v i n g passive a v o i d ance t r a i n i n g .  This f i n d i n g i n d i c a t e s  that the passive avoidance  t r a i n i n g procedure produced s i g n i f i c a n t l e a r n i n g which was s t a b l e over 11 days. also  The groups r e c e i v i n g passive avoidance t r a i n i n g were  combined. Figure 1 i l l u s t r a t e s  the median d r i n k i n g  l a t e n c i e s f o r the  groups r e c e i v i n g one of the ECS treatments f o l l o w i n g training.  The d r i n k i n g  passive avoidance  latency v a r i e s with both the type of ECS and  the time of ECS a d m i n i s t r a t i o n .  The s i n g l e 2.5 second ECS s i g n i f i -  c a n t l y impaired passive avoidance performance when presented  Table 2  D r i n k i n g L a t e n c i e s f o r the Groups i n Experiment 1 Which Did Not Receive ECS  Group  Test Latency (s econds) Median Rang;e  FS t e s t 48 h r s .  10  60. 0  a  15.6 - 60. 0  FS t e s t 11 days  10  60. 0  b  23.3 - 60. 0  FS Combined^  20  60.0  No FS t e s t 48 h r s .  5  2.3  1.6 - 4.3  No FS t e s t 11 days  7  2.0  2.0-4.0  12  2.0  1.6 - 4.3  No FS Combined  a  N  11  C  15.6 - 60. 0  S i g n i f i c a n t l y d i f f e r e n t from No FS t e s t 48 hours (p <.001).  b S i g n i f i c a n t l y d i f f e r e n t from No FS t e s t 11 days (p< .001). c  S i g n i f i c a n t l y d i f f e r e n t from Combined No FS group (p<.001).  d  The d i f f e r e n c e between the 48 hour and 11 day t e s t i n g s i s not significant.  immediately a f t e r t r a i n i n g 24 hours, or 9 days l a t e r  (p<(.001), but not when presented 1 hour, ( a l l comparisons are to the combined  shock-no ECS c o n t r o l s , o n e - t a i l e d ) .  foot-  The f i v e ECSs spaced 5 seconds  apart impaired performance when presented immediately (p< .001) or 1 hour  (p< .025) a f t e r t r a i n i n g , but not when presented at 24 hours.  I n c o n t r a s t , the f i v e ECSs spaced 1 minute apart impaired performance when presented immediately (p<£.001), 1 hour  (p<.001),  (p •(.Ol) and 48 hours (p<.02) but not 9 days a f t e r r e s u l t s show that each ECS formance which was of the ECS  24 hours  training.  These  treatment produced an impairment of per-  time-dependent.  These r e s u l t s a l s o show that each  treatments produced a g r a d i e n t of a d i f f e r e n t length.  Me-  dians, ranges and f u r t h e r s t a t i s t i c a l comparisons between these groups are presented i n Appendix A. None of the immediate ECS groups d i f f e r e d s i g n i f i c a n t l y from the eombined No FS c o n t r o l .  A l l other training-ECS groups were s i g n i f i -  cantly d i f f e r e n t from the No FS c o n t r o l s . The impairment of passive avoidance performance produced by the f i v e ECSs spaced 1 minute apart was appearing when t e s t i n g was  given 11 days r a t h e r than 48 hours a f t e r  t r a i n i n g , i n both the 1 hour p <.001) and the 24 hour conditions tailed) .  (compared  permanent over at l e a s t 11 days  (Median = 11.0, Range = 1.6 - 21.6;  (Median = 40.6, Range = 9.3 - 44.0; p<  to the combined  footshock-no ECS c o n t r o l s ,  .025) one-  These groups d i d not d i f f e r from the corresponding groups  tested at 48 hours. F i n a l l y , the three ECS  treatments given to animals not r e c e i v i n g  IMMED.  1 HR.  24 HR.  TIME OF F i g u r e 1. M e d i a n D r i n k i n g Latencies for the G r o u p s Receiving Passive A v o i d a n c e T r a i n i n g F o l l o w e d by o n e o f t h e ECS T r e a t m e n t s .  48 HR.  ECS  9 DAYS  footshock did not produce increased latencies as compared to the combined no footshock-no ECS controls (2.5 second ECS: f i v e ECSs, 5 seconds apart:  Median = 2.0;  Median = 2.3; f i v e ECSs, 1 minute apart:  Median = 2.3), showing that none of these treatments had a direct effect on the latency of the drinking response. Behavioral  Observations  The 2.5 second ECS consistently evoked a f u l l t o n i c - c l o n i c convulsion.  The f i v e ECSs spaced 5 seconds apart resulted i n only one  f u l l convulsion; however, each current onset was marked by a s l i g h t jerk.  The f i v e ECSs spaced 1 minute apart produced a separate re-  sponse to each stimulus:  to the f i r s t a t o n i c - c l o n i c convulsion, to  the second and third usually an i n i t i a l extension of the forelegs and opening of the mouth followed by a running seizure.  The fourth and  f i f t h ECSs produced s i m i l a r e f f e c t s , but were usually followed by more vigorous thrashing and running behavior. companied by vocalization.  These were often ac-  I t was frequently necessary to hold the  animal by the t a i l during these seizures to prevent his running off the feeding stand. Histology Following testing, the animals were k i l l e d ; the brains were removed and fixed i n formal saline. the cortex of any animal.  No hemorrhages were observed on  Two brains from animals which had received  the f i v e ECSs spaced 1 minute apart were sectioned at 40 microns and every f i f t h section for 1.5 millimeters anterior and posterior to the electrodes was taken and stained with thionin. Microscopic examination  42 revealed no gross morphological damage. Discussion A l l three ECS treatments produced impairments of passive avoidance which were time-dependent.  The time during which they were e f f e c t i v e  d i f f e r e d f o r each treatment; the single 2.5 second ECS produced a gradient of less than 1 hour, the f i v e ECSs spaced 5 seconds apart a gradient of between 1 and 24 hours, and the f i v e ECSs spaced 1 minute apart a gradient of between 48 hours and 9 days.  The greater impairment  produced by the longer spacings i s s i m i l a r to the findings reported by Brady et a l . (1954), and the present results confirm the reports of Brady (1952) and Williams (1963) that a series of ECSs can produce a long gradient.  In f a c t , the gradient of 48 hours produced by the f i v e  ECSs spaced 1 minute apart i s f a r greater than the longest gradient (6 hours) which has been reported with a single ECS (Kopp et a l . , 1966). A recent study (Weiner, 1970) has also found that a series of ECSs produced a longer gradient than a single ECS.  Using a m u l t i -  t r i a l shock-escape training procedure, he found that a series of four ECSs spaced 5 minutes apart impaired l a t e r performance when presented 5 or 30 minutes but not 24 hours after training.  In contrast, a single  ECS did not impair performance when presented at these times. However, Weiner also observed d e f i c i t s when either the series of ECSs or a single ECS were presented 7 or 14 days after t r a i n i n g , s i m i l a r to the effects found with anticholinesterase drugs (see page 69).  43  EXPERIMENT 2: OF  THE  ECSS TO ANESTHETIZED ANIMALS  A d i s t i n c t i o n has r e s p o n s e s p r o d u c e d by vations  t h a t t h e s e two  anticonvulsant ECS,  EFFECT OF PRESENTING A SERIES  drugs  been drawn b e t w e e n t h e i m p a i r m e n t s of  learned  s i n g l e and m u l t i p l e ECSs on the b a s i s of  obser-  treatments are d i f f e r e n t i a l l y a f f e c t e d  ( i . e . , McGaugh, 1 9 6 8 ) .  I n the c a s e of a s i n g l e  t h e d i s t u r b i n g e f f e c t on p e r f o r m a n c e i s s u p p o s e d l y u n a f f e c t e d  anticonvulsants  (Essman, 1968;  I n c o n t r a s t , m u l t i p l e ECS  B e c k w i t h , 1955).  ally,  a p p e a r t o have any  i s blocked  i n the  i t i s not  two  p o s s i b l e t o be  sure  t o the u s e  periments.  For  s e t s of e x p e r i m e n t s w e r e c o m p a r a b l e .  example, n e u r a l s e i z u r e d i s c h a r g e only  to block  I t i s d i f f i c u l t t o compare t h e d r u g and  discharge The  as w e l l as present  simply  l e v e l s of Specifichave  s e t s of  be  ECS  the s e i z u r e  t h a t the a n t i c o n v u l s a n t the o v e r t  ex-  necessary ECS  discharge.  l e v e l s used i n these  none of t h e s e e x p e r i m e n t s have i n c l u d e d  to c o n f i r m  Hunt &  the d r u g l e v e l s used i n the m u l t i p l e  s t u d i e s m i g h t have b e e n s u f f i c i e n t  recordings  may  per-  comparisons  of d i f f e r e n t d r u g l e v e l s i n the two  both e f f e c t s , but  p e r i m e n t s , and  e f f e c t on  t h a t the  may  by  Weissman, 1 9 6 5 ) .  (Hunt e t a l . , 1953;  the d i f f e r e n t i a l e f f e c t s of a n t i c o n v u l s a n t s  b e e n due  1966;  However, t h i s d i s t i n c t i o n i s b a s e d on  between s t u d i e s , and -anesthesia  McGaugh & A l p e r n ,  does not  f o r m a n c e when the c o n v u l s i o n  for  by  ex-  electrical  drugs blocked  the  convulsion.  e x p e r i m e n t examined the e f f e c t o f b l o c k i n g  the  seizure  c o n v u l s i o n on the i m p a i r m e n t of p a s s i v e a v o i d a n c e p e r f o r m a n c e  pro-  duced by f i v e ECSs s p a c e d 1 m i n u t e a p a r t .  I n o r d e r t o examine t h e  possibility  e f f e c t s of a n t i c o n v u l s a n t s  t h a t the r e p o r t e d d i f f e r e n t i a l  m i g h t be an a r t i f a c t o f d i f f e r e n t d r u g l e v e l s ,  the p r e s e n t e x p e r i m e n t  u s e d two d r u g s , b o t h of w h i c h b l o c k t h e o v e r t c o n v u s i o n , b u t w h i c h were found, through p r e l i m i n a r y r e c o r d i n g s , t o have q u i t e e f f e c t s on c o r t i c a l s e i z u r e d i s c h a r g e . e t h e r ) , was  found t o have l i t t l e  One  drug, ether  different  (diethyl  e f f e c t on s e i z u r e d i s c h a r g e , w h i l e  t h e o t h e r d r u g , sodium p e n t o b a r b i t a l , was  found to b l o c k or at  least  g r e a t l y a t t e n u a t e s e i z u r e d i s c h a r g e ( r e p r e s e n t a t i v e records are p r e sented i n Appendix C). Me thod S e v e n t y - s e v e n m a l e r a t s of t h e same age and s t r a i n a s t h o s e i n E x p e r i m e n t 1 were used h e r e . The a p p a r a t u s , s u r g i c a l and t o t h o s e used i n E x p e r i m e n t  t r a i n i n g p r o c e d u r e s were  identical  1.  The d e s i g n of t h e e x p e r i m e n t was  as f o l l o w s .  Ten g r o u p s , a l l  of w h i c h r e c e i v e d p a s s i v e a v o i d a n c e t r a i n i n g , w e r e t e s t e d .  Three  g r o u p s w e r e g i v e n t h e f i v e ECSs s p a c e d 1 m i n u t e a p a r t w h i l e a n e s t h e t i z e d w i t h e t h e r ( A n e s t h e t i c e t h e r , S q u i b b ) a t 1 hour hours  (n = 1 0 ) , o r 9 days  ( n = 10) a f t e r t r a i n i n g .  Three o t h e r groups  r e c e i v e d f i v e ECSs spaced 1 m i n u t e a p a r t u n d e r sodium anesthesia  ( N e m b u t a l , A b b o t t L a b o r a t o r i e s ) a t 1 hour  (n = 9 ) , or 9 d a y s  ( n = 6 ) , 24  pentobarbital (n = 7 ) , 24 h o u r s  (n = 6) .  To c o n t r o l f o r e f f e c t s of e t h e r o r sodium  pentobarbital alone  on p e r f o r m a n c e two g r o u p s were n o t g i v e n ECS b u t o n l y e t h e r sodium  p e n t o b a r b i t a l ( n = 7) a n e s t h e s i a 1 h o u r a f t e r  additional  ether  training.  sibility  training.  Two  g r o u p s w e r e i n c l u d e d ; t h e s e r e c e i v e d t h e 2.5 s e c o n d d u r -  a t i o n ECS u n d e r after  ( n = 6) o r  ( n = 8) o r s o d i u m p e n t o b a r b i t a l ( n = 8) 24 h o u r s  These g r o u p s w e r e i n c l u d e d s i m p l y t o examine  the pos-  t h a t e t h e r o r s o d i u m p e n t o b a r b i t a l m i g h t somehow augment t h e  e f f e c t o f ECS on p e r f o r m a n c e . Sodium p e n t o b a r b i t a l a n e s t h e s i a was p r o d u c e d b y i n j e c t i n g , peritoneally,  45 mg/kg o f s o d i u m p e n t o b a r b i t a l 15 m i n u t e s p r i o r  administration. thesia. jar  First,  A s t a n d a r d method was u s e d t o a d m i n i s t e r e t h e r the animals were p l a c e d  f o r approximately  45 s e c o n d s  (until  i n a 3-litre  ether  conds a f t e r b e i n g removed f r o m t h e j a r e t h e r was a g a i n  anes-  lost).  Fifteen seadministered  (a s m a l l v i a l c o n t a i n i n g e t h e r - s a t u r a t e d c o t t o n was f i t t e d snout).  t o ECS  saturated  t h e r i g h t i n g r e f l e x was  They were t h e n removed and t h e ECS c l i p s were a t t a c h e d .  intra-  over the  T h i s s e c o n d a d m i n i s t r a t i o n of e t h e r was n e c e s s a r y t o m a i n -  tain anesthesia.  The v i a l was o n l y k e p t o v e r t h e s n o u t f o r 15 s e c o n d s ,  and 15 s e c o n d s was a l w a y s a l l o w e d e t h e r and ECS. i n c l u d e d between  to e l a p s e between  a d m i n i s t r a t i o n of  A d d i t i o n a l 15-second a d m i n i s t r a t i o n s o f e t h e r were each ECS.  A l l a d m i n i s t r a t i o n s of e t h e r t o o k t h e  same f o r m w h e t h e r ECS was a d m i n i s t e r e d A l l a n a l y s e s , as i n t h e p r e v i o u s  or n o t . e x p e r i m e n t , were p e r f o r m e d on  the mean d r i n k i n g l a t e n c i e s f o r each a n i m a l on t h e t e s t d a y , u s i n g Halperin's  (1960) e x t e n s i o n o f t h e Mann-Whitney  test.  46 Results The f i v e ECSs spaced 1 minute apart, when presented to animals anesthetized with ether or sodium p e n t o b a r b i t a l , produced the same impairments of passive avoidance performance as had been found i n the previous experiment using unanesthetized animals (Figure 2). The f i v e ECSs spaced 1 minute apart under ether produced  significantly  lower d r i n k i n g l a t e n c i e s than the ether only c o n t r o l s when administered a t 1 hour  (p<.02) and 24 hours (p<.02), but not a t 9 days  after  Similarly,  training.  the f i v e ECSs spaced 1 minute apart under  sodium p e n t o b a r b i t a l produced s i g n i f i c a n t l y when administered a t 1 hour 9 days a f t e r are  training.  lower.drinking  latencies  (p (.01) or 24 hours (p <f.01) , but not a t  A d d i t i o n a l comparisons between these groups  presented i n Appendix B. There were no d i f f e r e n c e s between the ether and sodium pento-  barbital  groups under any of the c o n d i t i o n s .  groups d i f f e r e d  Moreover, none of these  s i g n i f i c a n t l y from the corresponding groups i n Exper-  iment 1. The 2.5 second ECS a t 24 hours under ether (Median = 60.0, Range = 12.0 - 60.0) or sodium p e n t o b a r b i t a l = 26.6 - 60.0) d i d not s i g n i f i c a n t l y the  (Median = 60.0, Range  impair performance r e l a t i v e to  groups r e c e i v i n g only ether or sodium p e n t o b a r b i t a l .  ing suggests that anesthesia d i d not augment the e f f e c t  This  find-  of ECS on  performance. Behavioral Observations Both ether and sodium p e n t o b a r b i t a l blocked the overt convulsion  I 47 to the extent that the response to ECS was fening during c u r r e n t p r e s e n t a t i o n .  Two  only a b r i e f j e r k or s t i f -  animals r e c e i v i n g ECS under  ether showed evidence of a motor s e i z u r e during ECS and were discarded from the  experiment. Discussion  Ether and sodium p e n t o b a r b i t a l a n e s t h e s i a , both of which blocked overt signs of a s e i z u r e , d i d not attenuate the e f f e c t of a s e r i e s of f i v e ECSs.  Under both drugs, the f i v e ECSs spaced  1 minute apart  paired performance of the passive avoidance response gree as had been found with unanesthetized animals  im-  to the same de-  i n the previous  experiment. • i  The present f i n d i n g s are i n c o n t r a s t to those of Hunt, et a l . , (1953) and Hunt and Beckwith  (1955) who  found that b l o c k i n g the be-  h a v i o r a l convulsion also blocked the e f f e c t of a s e r i e s of ECSs on performance.  Conversely, the present f i n d i n g s are c o n s i s t e n t with  the r e s u l t s u s u a l l y obtained with a s i n g l e ECS & Alpern, 1966;  Weissman, 1965).  (Essman, 1968;  These r e s u l t s , t h e r e f o r e , do not  support the hypothesis that the gradient produced .  ECSs spaced  McGaugh  by the s e r i e s of  1 minute apart represents a d i f f e r e n t process than that  r e s p o n s i b l e f o r s i n g l e ECS g r a d i e n t s . ;  McGaugh and Zornetzer (1970) have r e c e n t l y reported  evidence  which a l s o questions the d i s t i n c t i o n between s i n g l e and m u l t i p l e ECS gradients.  In t h e i r experiment,  mice trained i n a passive avoidance  task were l a t e r given ECS e i t h e r while anesthetized with ether or t  i ')  while unanesthetized.  They found the ECS  gradient was  blocked i f a  I  NO ECS  I  1 HR.  Median Drinking Latencies for the Groups Receiving 5 E C S ' S Spaced 1 Minute apart U n d e r Ether or S o d i u m Pentobarbital A n e s t h e s i a F o l l o w i n g Passive A v o i d a n c e T r a i n i n g .  I  24 HR.  1 9 DAYS  49  low intensity ECS and high concentration of ether were used, but not when either a high intensity ECS or low concentration of ether was used.  I t now appears that both single and multiple ECS gradients may  or may not be blocked by anticonvulsant drugs. The reason why anticonvulsant drugs i n some cases block the ECS gradient i s presumably because i n those cases some aspect of the neuronal disturbance which i s normally produced by ECS and which i s necessary to produce the ECS gradient i s blocked.  McGaugh and Zornetzer  (1970) reported that animals administered low intensity ECS under high concentrations of ether did not exhibit any disturbance of corti c a l neuronal a c t i v i t y as a result of the ECS, although c o r t i c a l seizures were observed i n those animals administered either high i n tensity ECS or low intensity ECS under low concentrations of ether. Therefore the condition i n which they observed the ECS gradient to be -blocked corresponded  to the condition i n which ECS did not produce a  detectable neuronal disturbance. In this experiment the ECS gradient appeared under a l l conditions, presumably because the ECS intensity was high r e l a t i v e to the levels of drugs used.  Nevertheless, i n the case of sodium pentobar-  b i t a l anesthesia an interesting result was obtained.  The l e v e l of  sodium pentobarbital anesthesia used here was found to block or greatly attenuate the c o r t i c a l seizure discharge normally produced by ECS suggesting that seizure discharge, at least i n the cortex, i s not necessary for the gradient produced by the series of ECSs.  This  result i s not inconsistent with the results of McGaugh and Zornetzer  50 (1970), since i n the present experiment other aspects of the neuronal disturbance such as the period of p o s t - i c t a l depression were not blocked by the drug.  More research i s needed to c l a r i f y which as-  pects of the disturbance produced by ECS are responsible for producing the ECS gradient.  51  EXPERIMENT 3: EFFECT OF A SERIES OF ECSS ON AN APPETITIVE RESPONSE ACQUIRED IN A SINGLE TRIAL  The f i r s t two experiments established that f i v e ECSs spaced 1 minute apart produced a longer gradient i n a passive avoidance task than has been found with a single ECS.  This gradient does not appear  to d i f f e r except i n magnitude from those produced by a single ECS. The present experiment examined the generality of this increased impairment by using a o n e - t r i a l appetitive training procedure.  This  task involves a quite different response (approach) than the previous passive avoidance task ( i n h i b i t i o n of approach). Method One hundred and thirteen rats of the same s t r a i n as i n Experiments 1 and 2 were used i n this experiment.  Of these, 40 were ex-  cluded for f a i l i n g to l i c k the spout with 10 minutes on the training day, leaving only 73 subjects. The apparatus and surgical procedures were i d e n t i c a l to those of Experiments 1 and 2.' The animals also received the same treatment as those i n the previous experiments u n t i l the f i r s t pretraining day. On this day, they were each placed i n the a l l e y for 10 minutes with the water spout empty.  The number of l i c k s at the empty spout was  recorded on the drinkometer. procedure was followed.  For the next two days the i d e n t i c a l  The animals received 1 hour of access to  water i n their home cages following removal from the a l l e y .  On the fourth day, appetitive training was carried out. The animals were placed i n the a l l e y as usual, only on this day the water spout contained water. to drink for 15 seconds.  Those animals finding the water were allowed They were then removed and the wires for ad-  ministering ECS were attached. Three ECS treatments were used i n this experiment.  Two of these, f i v e ECSs spaced 1 minute apart and one 2.5  second duration ECS were the same as those used i n the previous experiments.  A third ECS treatment, one 0.5 second duration ECS, was also  examined. Separate groups received the f i v e ECSs spaced 1 minute apart at 15 seconds (n =5) or 1 hour (n = 7) following t r a i n i n g .  Similarly,  the one ECS of 2.5 seconds duration was given at 15 seconds (n = 5) and 1 hour (n = 9) after t r a i n i n g .  The one ECS of 0.5 seconds duration  was also given at 15 seconds (n = 5) and 1 hour (n = 8). The 15 second delay was required to attach the wires. feeding stand beside the a l l e y .  ECS was always given on a  The 1 hour delay animals were returned  to their home cages for the hour. To determine the aversiveness of the three ECS treatments, three control groups (n = 5 each) were not given water on the training day but were removed 15 seconds after f i r s t touching the spout (the time allowed the other groups for drinking) and were given one of the three ECS treatments 15 seconds l a t e r . Two groups were not given ECS: one received water (appetitive training, n = 10), the other (n = 9) did not. A l l animals were given 1 hour access to water i n their home cages either 1 hour after ECS or  53 1 hour a f t e r  the t r a i n i n g  trial.  F o r a l l g r o u p s , t e s t i n g was  g i v e n 48 h o u r s a f t e r  training,  and  c o n s i s t e d of r e c o r d i n g t h e number o f l i c k s a t t h e empty s p o u t i n a m i n u t e s e s s i o n as on p r e t r a i n i n g d a y s .  Comparisons  between groups  were made on t h e b a s i s of t h e number of l i c k s on t h e t e s t day. d a t a were a n a l y s e d u s i n g n o n - p a r a m e t r i c t e s t s  10  The  (Mann-Whitney U ) .  Results The a p p e t i t i v e t r a i n i n g p r o c e d u r e p r o d u c e d an i n c r e a s e i n the amount of l i c k i n g a t t h e empty s p o u t on t h e t e s t day. c e i v i n g water  The  ( a p p e t i t i v e t r a i n i n g ) on the t r a i n i n g day  Range = 4 - 266) showed a s i g n i f i c a n t l y  group r e -  ( M e d i a n = 95,  (U = 7, p < .001)  g r e a t e r num-  b e r of l i c k s a t t h e s p o u t on t h e t e s t day t h a n t h e g r o u p n o t g i v e n water  ( M e d i a n = 8, Range = 1 - 2 4 ) .  This r e s u l t demonstrates that  d r i n k i n g e x p e r i e n c e on t h e t r a i n i n g day p r o d u c e d  substantial  the  learning  of t h e p r e s e n c e o f w a t e r i n t h e s p o u t . R e s u l t s f o r the groups r e c e i v i n g a p p e t i t i v e t r a i n i n g f o l l o w e d one of t h e ECS  t r e a t m e n t s a r e p r e s e n t e d i n T a b l e 3.  were o b s e r v e d b e t w e e n the t h r e e ECS  treatments.  No  by  differences  E a c h ECS  treatment  p r o d u c e d s i g n i f i c a n t i m p a i r m e n t o f t h e a p p e t i t i v e r e s p o n s e when p r e s e n t e d 15 s e c o n d s a f t e r  t r a i n i n g , b u t n o t when p r e s e n t e d 1 hour  after  training. I n s p e c t i o n of t h e m e d i a n number o f l i c k s f o r the t h r e e g r o u p s r e c e i v i n g ECS  a t 1 hour a f t e r  t r a i n i n g shows t h a t t h e s e s c o r e s a r e  somewhat l o w e r t h a n t h e m e d i a n f o r t h e no ECS, H2O d i f f e r e n c e m i g h t s u g g e s t t h a t some i m p a i r m e n t was  control. still  This  produced  by  54 Table 3  Number of Licks at the Empty Water Spout on the Test Day for the Groups i n Experiment 3  Type of ECS  Time of ECS  No ECS H 0 Control 2  N  Median  10  95  No ECS No H 0 Control  1 ECS, 2.5 sec. duration  5 ECSs, 1 min. apart  a  7***  42  4**  9*  15 sec.  22  17  1 hr.  53  22 - 254  1***  35  4**  10* 43  15 sec.  5  43  14 -  1 hr.  9  54  30 - 248  0***  15 sec.  39  11 _ 48  4**  1 hr.  62  17 - 234  3**  Compared to No ECS, No H 0 Control  a  2  b  266  U  1-24  2  1 ECS, 0.5 sec. duration  Range  Compared to No ECS, H 0 Control 2  *  p<.05  (one-tailed)  **  p<.01  (one-tailed)  ***  p^.001  (one-tailed)  68  9* 32  the ECS treatments when administered at this time, even though the i n d i v i d u a l comparisons to the no ECS,  control were not s i g n i f i c a n t .  However, this p o s s i b i l i t y i s not supported by the finding that even when combined, these three groups do not d i f f e r from the no ECS,  H0 2  control (U = 110, n.s.). A l l groups receiving appetitive training followed by ECS showed s i g n i f i c a n t l y higher numbers of l i c k s at the empty spout than the cont r o l group which had not received appetitive training (Table 3). These differences suggest that s i g n i f i c a n t retention of the appetitive t r a i n ing was present i n every group. The results from the control groups receiving only ECS on the training day indicate that the impaired performance found with the f i v e ECSs spaced 1 minute apart and the 2.5 second duration ECS were not due to punishment.  ECS alone did not affect the number of l i c k s  ( r e l a t i v e to the control group not receiving appetitive training) i n the f i v e ECSs spaced 1 minute apart condition (Median = 4, Range = 0 - 76, U = 19) or the 2.5 second duration ECS condition (Median = 0, Range = 0 - 106, U = 17).  If ECS was aversive, i t would be ex-  pected to decrease the frequency of a response which preceded i t . Because these two treatments did not decrease the.number of l i c k s , the impairment found i n the groups given these treatments 15 seconds after appetitive training cannot be explained by punishment.  On the  other hand, the single 0.5 second duration ECS produced a s i g n i f i c a n t l y lower number of l i c k s (Median = 1, Range = 0 - 2, U = 3; p ^ . O l ) , i n dicating that administration of this treatment may have been aversive.  Discussion In the a p p e t i t i v e task used here, there were no d i f f e r e n c e s between the lengths of the gradients produced by the three ECS The  f i v e ECSs spaced 1 minute apart produced only a s l i g h t  of performance when presented ment when presented  treatments.  impairment  15 seconds a f t e r t r a i n i n g , and no impair-  1 hour a f t e r t r a i n i n g .  I t should be pointed out  that the s u b j e c t s r e c e i v i n g a p p e t i t i v e t r a i n i n g showed considerable variability  i n the response measure used i n t h i s task.  I t i s possible  that t h i s v a r i a b i l i t y masked small d i f f e r e n c e s between the ECS t r e a t ments, although observed  i t i s q u i t e u n l i k e l y that d i f f e r e n c e s of the magnitude  i n Experiments 1 and 2 would not have been detected.  Because of the low response l e v e l i n the groups not given a p p e t i t i v e t r a i n i n g , the adequacy of the c o n t r o l s f o r a v e r s i v e e f f e c t s of ECS might be questioned.  A v e r s i v e e f f e c t s might not have been detected  because the animals were already responding  a t such a low r a t e .  How-  ever, i n the case of the f i v e ECSs spaced 1 minute apart and the s i n g l e 2.5 second d u r a t i o n ECS, no a v e r s i v e e f f e c t s were detected i n E x p e r i ment 1 (or i n t h i s experiment) and i t therefore appears safe to i n t e r pret the d e f i c i t s produced by these treatments as amnesia.  i n t h i s a p p e t i t i v e task  On the other hand, the s i n g l e 0.5 second d u r a t i o n ECS,  which was not examined i n Experiment 1, appeared to produce s i g n i f i c a n t a v e r s i v e e f f e c t s i n t h i s a p p e t i t i v e task.  Therefore i t i s p o s s i b l e  that the gradient produced by t h i s treatment  was due to punishment,  not amnesia. The  length of the gradients produced by each of the ECS  treatments  i n this task, between 15 seconds and 1 hour, i s shorter than the 3 hours found by Tenen (1965b) but i s somewhat comparable to those reported by P i n e l (1969), 1 minute, and Herz (1969), 20 seconds, a l l of whom used a single ECS and appetitive tasks.  However, t h i s gradient  i s much shorter than the gradient found with f i v e ECSs spaced 1 minute apart i n the passive avoidance task (Experiments 1 and 2).  I t should  be noted that even i f a l l three gradients are interpreted as r e f l e c t i n g aversive e f f e c t s , the main conclusion of this experiment, namely that the series of ECSs did not produce a longer gradient than a single ECS i n this task, i s unchanged. The f a i l u r e to observe v a r i a b i l i t y i n the lengths of the gradients produced by the d i f f e r e n t ECS treatments i s not inconsistent with a v a i l able data.  No study has previously examined the effects of varying ECS  parameters i n a o n e - t r i a l appetitive task, although a comparison of the results of P i n e l (1969) and Tenen (1965b) suggests that ECS intensity may affect the length of the gradient i n an appetitive task.  P i n e l used  60 ma. and found a gradient of 1 minute; Tenen used 150 ma. and found a gradient of 3 hours. The present results are consistent with those of Sidman et a l . , (1955) who found that a series of ECSs impaired the performance of a CER, but not a more recently acquired appetitive response (bar press). The results of Sidman et a l . (1955) and of the present experiment suggest that a series of ECSs i s more effective i n producing a long gradient when a shock-motivated appetitive response i s used.  inhibitory response i s used than when an  58  GENERAL DISCUSSION  T h r e e i s s u e s w i l l be d i s c u s s e d  here:  f i r s t , the p o s s i b i l i t y  that  memory c o n s o l i d a t i o n i s r e l a t i v e l y b r i e f and i s m a x i m a l l y d i s t u r b e d b y a s i n g l e ECS; s e c o n d , p o s s i b l e e x p l a n a t i o n s obtained  f o r the d i f f e r e n t  results  i n t h e p a s s i v e a v o i d a n c e and a p p e t i t i v e t a s k s ; and t h i r d , t h e  e f f e c t o f ECS on t h e c o n s o l i d a t i o n  process.  ECS  Gradients  The  d u r a t i o n o f t i m e r e q u i r e d f o r memory c o n s o l i d a t i o n i s u s u a l l y  estimated as ECS.  and t h e D u r a t i o n  o f Memory C o n s o l i d a t i o n  f r o m t h e l e n g t h of t h e g r a d i e n t s Because the l e n g t h s  p r o d u c e d by t r e a t m e n t s s u c h  of such g r a d i e n t s vary  somewhat w i t h  t r e a t m e n t p a r a m e t e r s , i t seems p r o b a b l e t h a t c o n s o l i d a t i o n  continues  •for a t l e a s t as l o n g as t h e l e n g t h o f t h e l o n g e s t g r a d i e n t w h i c h c a n be o b t a i n e d .  However, t h e r e i s a n o t h e r p o s s i b i l i t y , namely t h a t mem-  o r y c o n s o l i d a t i o n i s m a x i m a l l y d i s t u r b e d by a s i n g l e ECS, and t h a t longer gradients process.  obtained  w i t h other  treatments r e f l e c t  some o t h e r  The v i e w t h a t a s i n g l e ECS m a x i m a l l y d i s r u p t s t h e c o n s o l i -  d a t i o n p r o c e s s o r i g i n a t e d f r o m d u a l p r o c e s s t h e o r i e s of c o n s o l i d a t i o n ( e . g . , Hebb, 1 9 4 9 ) , i n w h i c h ECS was assumed t o d i s r u p t neural f i r i n g .  patterned  While such t h e o r i e s a r e s e r i o u s l y questioned  by t h e  f i n d i n g of v a r i a b i l i t y i n ECS g r a d i e n t s w i t h ECS p a r a m e t e r s , t h e v i e w t h a t s i n g l e ECS g r a d i e n t s s o l i d a t i o n has l i n g e r e d on.  reflect  a maximal d i s t u r b a n c e  of c o n -  C o n s o l i d a t i o n i s g e n e r a l l y assumed t o  59 be  c o m p l e t e w i t h i n a few m i n u t e s o r a t l o n g e s t a few h o u r s a f t e r  ing, corresponding The  present  train-  t o t h e l e n g t h of ECS g r a d i e n t s . i n v e s t i g a t i o n a t t e m p t e d t o show t h a t g r a d i e n t s  be p r o d u c e d w i t h a s e r i e s o f ECSs w h i c h w e r e l o n g e r gradients but not otherwise  different.  could  t h a n s i n g l e ECS  Such a f i n d i n g w o u l d be i n c o n -  s i s t e n t w i t h t h e p o s i t i o n t h a t s i n g l e ECS g r a d i e n t s r e f l e c t a m a x i m a l d i s r u p t i o n o f memory c o n s o l i d a t i o n , and w o u l d i n s t e a d s u g g e s t memory c o n s o l i d a t i o n c o n t i n u e s  that  f o r a longer p e r i o d than i s estimated  f r o m t h e l e n g t h of s i n g l e ECS g r a d i e n t s . I n E x p e r i m e n t 1, i n w h i c h a p a s s i v e a v o i d a n c e t r a i n i n g  procedure  was u s e d , a s e r i e s o f f i v e ECSs s p a c e d 1 m i n u t e a p a r t p r o d u c e d a g r a d i e n t of 48 h o u r s , s u b s t a n t i a l l y l o n g e r t h a n t h e g r a d i e n t  ( l e s s than 1  h o u r ) p r o d u c e d by a s i n g l e ECS.  This gradient i s also of greater  l e n g t h than the longest g r a d i e n t  (6 h o u r s ) w h i c h h a s p r e v i o u s l y b e e n  r e p o r t e d w i t h a s i n g l e ECS (Kopp e t a l . , 1 9 6 6 ) . W h i l e t h e g r a d i e n t o f 48 h o u r s f o u n d i n E x p e r i m e n t 1 i s c o n s i d e r a b l y l o n g e r t h a n t h e d u r a t i o n o f t i m e t h a t memory c o n s o l i d a t i o n i s g e n e r a l l y assumed t o c o n t i n u e  f o r , i t i s comparable i n l e n g t h to the  g r a d i e n t s f o u n d i n two o t h e r r e c e n t found t h a t impaired  B u r e s o v a and B u r e s  KC1 a p p l i e d t o t h e c o r t e x o f r a t s f o r a p r o l o n g e d  l a t e r performance of a shock-motivated  when a d m i n i s t e r e d i l a r l y , Cherkin impaired  studies.  period  pattern discrimination  24 h o u r s b u t n o t 14 days f o l l o w i n g t r a i n i n g . (1969) showed t h a t h i g h c o n c e n t r a t i o n s  passive avoidance behavior  b u t n o t 48 h o u r s a f t e r  training.  (1971)  Sim-  of f l u r o t h y l  i n c h i c k s when p r e s e n t e d  24 h o u r s  Experiment 2 examined whether the long gradient found with s e r i e s of ECSs i n Experiment 1 was ECS  gradients.  The  and m u l t i p l e ECS  q u a l i t a t i v e l y d i f f e r e n t from s i n g l e  primary support  f o r a d i s t i n c t i o n between s i n g l e  gradients comes from studies showing that a n t i c o n -  v u l s a n t drugs blocked et a l . , 1953;  the  the gradients produced by m u l t i p l e ECSs (Hunt  Hunt & Beckwith, 1955)  McGaugh & A l p e r n , 1966;  but not s i n g l e ECSs (Essman,  Weissman, 1965).  1968;  In Experiment 2 a s e r i e s of  f i v e ECSs spaced 1 minute apart were s t i l l found to produce a long gradient when presented both of which blocked  under ether or sodium p e n t o b a r b i t a l anesthesia,  overt signs of a convulsion.  This f i n d i n g i s  opposite to the r e s u l t s p r e v i o u s l y reported with m u l t i p l e ECSs, but s i m i l a r to those found with s i n g l e ECSs.  Therefore  i t i s probable  that the d i f f e r e n c e s p r e v i o u s l y found between the e f f e c t s of a n t i convulsant  drugs on s i n g l e and m u l t i p l e ECS  .different drug l e v e l s or ECS and not due  gradients were due  to  parameters i n the d i f f e r e n t experiments,  to a q u a l i t a t i v e d i f f e r e n c e between the gradients  pro-  duced by s i n g l e and m u l t i p l e ECSs. The  r e s u l t s of a recent study by McGaugh and  also i n d i c a t e that the d i f f e r e n c e s reported and m u l t i p l e ECS s i n g l e ECS  The  e a r l i e r between s i n g l e  invalid.  They found that  and a high concentration of ether were used, but  e i t h e r a high i n t e n s i t y ECS  used.  (1970)  gradients could be blocked by ether anesthesia i f a low  i n t e n s i t y ECS if  gradients are probably  Zornetzer  not  or low concentration of ether were  f i n d i n g s of McGaugh and  Zornetzer  (1970) together  with  the r e s u l t s of Experiment 2 suggest that a d i s t i n c t i o n between  61 s i n g l e and m u l t i p l e ECS g r a d i e n t s on the b a s i s of supposed d i f f e r e n t i a l e f f e c t s of a n t i c o n v u l s a n t drugs i s i n c o r r e c t . A q u a l i t a t i v e d i s t i n c t i o n between s i n g l e and m u l t i p l e ECS gradi e n t s i s not supported any other evidence.  by the e f f e c t s of a n t i c o n v u l s a n t drugs, nor by  The longer g r a d i e n t s produced by a s e r i e s of ECSs  l i k e l y r e f l e c t a g r e a t e r d i s t u r b a n c e of the same u n d e r l y i n g  process  which i s d i s t u r b e d by a s i n g l e ECS. Assuming that ECS g r a d i e n t s r e f l e c t the d i s t u r b a n c e of memory c o n s o l i d a t i o n , the c o n c l u s i o n f o l l o w s from the r e s u l t s of Experiments 1 and 2 that the c o n s o l i d a t i o n process f o r t h i s p a s s i v e avoidance response continues f o r at l e a s t 48 hours. While a s e r i e s of ECSs produced a long g r a d i e n t i n the p a s s i v e avoidance t a s k , i t d i d not produce a longer g r a d i e n t than a s i n g l e ECS (of 0.5 or 2.5 seconds d u r a t i o n ) i n a one t r i a l a p p e t i t i v e task. A l l three treatments  produced only a s l i g h t impairment a t 15 seconds,  and none a t 1 hour.  This f i n d i n g has a number of p o s s i b l e i m p l i c a -  t i o n s which w i l l be considered  i n the next s e c t i o n .  P a s s i v e Avoidance - A p p e t i t i v e Task D i f f e r e n c e s The f i n d i n g that a s e r i e s of ECSs spaced 1 minute apart produced g r a d i e n t s of q u i t e d i f f e r e n t lengths i n the passive avoidance and a p p e t i t i v e tasks i s not p r e d i c t e d by c o n s o l i d a t i o n theory, but i s from two other p o s i t i o n s (Posluns & Vanderwolf, 1970; Spevack & Suboski, 1969) both of which do not view ECS g r a d i e n t s i n p a s s i v e avoidance tasks as evidence f o r memory c o n s o l i d a t i o n .  Nevertheless,  this finding i s not inconsistent with consolidation theory, and can b explained from a consolidation position i n two ways.  These four view  points w i l l be considered here. Incubation theory, as presented by Spevack and Suboski  (1969),  holds that ECS gradients i n passive avoidance tasks r e f l e c t the h a l t ing of an incubation process, not interference with memory consolidation.  The strength of the learned response i s assumed to increase  (incubate) following t r a i n i n g , and ECS i s assumed to h a l t this incubation process.  On the other hand, brief ECS gradients (less than  1 minute) which have been found i n appetitive and discriminated avoidance tasks were assumed to r e f l e c t a true interference with cons o l i d a t i o n since the learned responses i n these tasks do not appear to incubate.  According to their theory, a short gradient would be  predicted i n the appetitive task since responses i n such tasks pre' sumably do not incubate.  The passive avoidance task might be ex-  pected to y i e l d a longer gradient since the learned response might undergo a long incubation period. However, there i s some direct evidence against Spevack and Suboski's incubation hypothesis. ient  Tenen (1966b) found a long grad-  (3 hours) i n a one t r i a l appetitive task.  In. addition, Bailey  et a l . (1970) and P i n e l (1970) found no evidence for incubation i n passive avoidance tasks which yielded long gradients.  Incubation  theory has one other serious flaw; because ECS i s assumed to halt the incubation process the theory i s incapable of explaining v a r i a b i l i t y i n ECS gradients with current parameters.  Therefore, while  63 i n c u b a t i o n theory p r e d i c t s d i f f e r e n t length g r a d i e n t s i n p a s s i v e avoidance and a p p e t i t i v e s i t u a t i o n s , as p r e s e n t l y formulated  i t is  inadequate to account f o r the present f i n d i n g s . Posluns and Vanderwolf (1970) suggested that ECS has two e f fects:  first,  i t impairs i n h i b i t i o n of responding;  and second, i f  presented w i t h i n a few seconds of t r a i n i n g i t can d i s r u p t memory consolidation.  They suggest that ECS produces long g r a d i e n t s i n  tasks where response i n h i b i t i o n f a c i l i t a t e s the learned response, such as the passive avoidance, but not i n tasks where response i n h i b i t i o n i s incompatible with the learned response, such as a p p e t i t i v e tasks.  However, t h e i r theory evades the c r i t i c a l question of  how a time-dependent e f f e c t dependent e f f e c t longer g r a d i e n t .  (amnesia) combines with the non-time-  (impairment of response i n h i b i t i o n ) to produce a Therefore  t h i s theory i s not able to account f o r  the time dependence of the long gradient found here with a s e r i e s of ECSs. I t should be pointed out the theory of Posluns and Vanderwolf o f f e r s an i n t e r e s t i n g explanation f o r the f a i l u r e of the s e r i e s of ECSs to produce a longer gradient than a s i n g l e ECS i n the a p p e t i t i v e task.  They have shown that a s e r i e s of ECSs produces greater  impair-  ment of response i n h i b i t i o n than a s i n g l e ECS (Posluns & Vanderwolf, 1970).  I f a s e r i e s of ECSs a l s o produces a greater disturbance of  memory c o n s o l i d a t i o n than a s i n g l e ECS, these two e f f e c t s could have c a n c e l l e d one another so that both treatments produced gradients of s i m i l a r length.  From a c o n s o l i d a t i o n p o i n t of view, the most l i k e l y  explanation  for  the d i f f e r e n t length g r a d i e n t s  two  tasks i s that the c o n s o l i d a t i o n processes r e q u i r e d i f f e r e n t times  to reach completion.  produced by a s e r i e s of ECSs i n the  S e v e r a l s t u d i e s have shown that the l e n g t h of  the g r a d i e n t produced by ECS  depends on a number of v a r i a b l e s which do  not l i k e l y a f f e c t the n e u r a l d i s t u r b a n c e may  produced by ECS,  exert t h e i r e f f e c t through "speeding up"  but which  the c o n s o l i d a t i o n process.  These v a r i a b l e s i n c l u d e p r i o r experience w i t h the t r a i n i n g apparatus ( M i l l e r , 1970), the l e v e l of footshock used (Ray & Bivens, 1968), and the nature of the t r a i n i n g procedure (Chorover & S c h i l l e r , 1966). Some c h a r a c t e r i s t i c s of the a p p e t i t i v e t r a i n i n g used here may  have been  more conducive to r a p i d c o n s o l i d a t i o n than the c h a r a c t e r i s t i c s of  the  passive avoidance t r a i n i n g procedure. There i s a second e x p l a n a t i o n f o r the passive  avoidance-appetitive  ' d i f f e r e n c e which i s a l s o c o n s i s t e n t w i t h c o n s o l i d a t i o n theory. than r e f l e c t i n g d i f f e r e n c e s i n the d u r a t i o n of the two  Rather  consolidation  processes, the d i f f e r e n t l e n g t h gradients might r e f l e c t d i f f e r e n c e s i n the s u s c e p t i b i l i t y of the two c o n s o l i d a t i o n processes to d i s r u p t i o n . A s e r i e s of ECSs might produce a more pronounced disturbance  of  the  c o n s o l i d a t i n g p a s s i v e avoidance memory than of the c o n s o l i d a t i n g appeti t i v e memory, even though the two processes might r e q u i r e s i m i l a r times to reach completion.  This could happen f o r example i f the two memories  were being stored i n d i f f e r e n t areas of the b r a i n , which were d i f f e n t i a l l y . a f f e c t e d by ECS.  There i s evidence that l i m b i c s t r u c t u r e s  be i n v o l v e d i n the c o n s o l i d a t i o n of passive avoidance responses  may  (Barcik, 1969; Kesner & Doty, 1968) and limbic areas are known to be highly susceptible to seizures. Unfortunately the brain structures involved i n the storage of appetitive responses have not as yet been investigated. The f a i l u r e of the series of ECSs spaced 1 minute apart to produce a longer gradient than a single ECS i n the one t r i a l appetitive task suggests that the process being disturbed i n this task d i f f e r s from that responsible for the long gradient i n the passive avoidance task.  While the nature of the differences between these processes i s  s t i l l unclear, i t should be emphasized that this finding does not imply that ECS gradients i n the passive avoidance task do not r e f l e c t memory consolidation. On the contrary, the explanation for the gradient i n the passive avoidance task which i s consistent with the l a r g est amount of data i s that of a disruption of memory consolidation. The d i f f e r e n t findings obtained with a series of ECSs i n the passive avoidance and appetitive tasks may indicate either that the consolidation processes i n the two tasks require d i f f e r e n t times to reach completion or that somewhat d i f f e r e n t changes are involved i n consolidation of the two memories. The gradient of 48 hours found i n Experiment 1 does not appear to be q u a l i t a t i v e l y different from shorter gradients produced by a single ECS, nor does i t appear to be due to some process other than a disturbance of memory consolidation. Instead, this long gradient seems to be best explained by the assumption that memory consolidation continues for at least 48 hours after training i n this passive  avoidance task.  Although 48 hours i s c o n s i d e r a b l y  longer  than c o n s o l -  i d a t i o n has been g e n e r a l l y assumed to continue f o r , i t appears necessary t o conclude that the c o n s o l i d a t i o n process may i n some cases cont i n u e f o r at l e a s t t h i s l e n g t h of time.  However, i t i s s t i l l necessary  to e x p l a i n why even though c o n s o l i d a t i o n continues f o r t h i s l o n g , a s i n g l e ECS may s t i l l produce only a b r i e f g r a d i e n t .  I n order to c l a r -  ify  the mechanism r e s p o n s i b l e f o r v a r i a t i o n s i n ECS g r a d i e n t s  with  ECS  parameters, the next s e c t i o n examines the nature of the e f f e c t of  ECS  on the c o n s o l i d a t i o n process.  The E f f e c t of ECS on the C o n s o l i d a t i o n Process The  e a r l y view of memory c o n s o l i d a t i o n was a process by which  i n f o r m a t i o n was transformed from a l a b i l e memory t r a c e to a s t a b l e permanent memory ( f o r example, Hebb, 1949). was assumed t o i n v o l v e patterned  The i n i t i a l l a b i l e t r a c e  n e u r a l f i r i n g , the c o n t i n u a t i o n of  which was necessary f o r the permanent memory to be e s t a b l i s h e d . sequently,  Con-  ECS was assumed to stop the c o n s o l i d a t i o n process, s i n c e  by d i s r u p t i n g the patterned  f i r i n g f u r t h e r memory was prevented from  e n t e r i n g the s t a b l e s t a t e .  Accordingly,  the amount of memory a v a i l -  able to the animal a t the time of t e s t i n g corresponded to the amount which had entered the permanent s t a t e at the time ECS was  administered.  However, the e a r l y dual t r a c e theory of c o n s o l i d a t i o n cannot adequately e x p l a i n why, f o r example, the d i f f e r e n t i n t e n s i t i e s of ECS produce d i f f e r e n t length g r a d i e n t s . be viewed as stopping  C l e a r l y both i n t e n s i t i e s cannot  the c o n s o l i d a t i o n process.  An a l t e r n a t i v e  f o r m u l a t i o n of the e f f e c t of ECS on the c o n s o l i d a t i o n process i s r e quired to account f o r t h i s v a r i a b i l i t y i n the ECS g r a d i e n t w i t h ECS parameters. A second f i n d i n g which i s a l s o d i f f i c u l t to r e c o n c i l e w i t h the e a r l y d u a l process model i s t h a t the g r a d i e n t s produced by ECS a r e o c c a s i o n a l l y only temporary and i f the time of t e s t i n g i s delayed the d e f i c i t disappears (e.g., Pagano et a l . , 1969).  I f ECS had stopped  the c o n s o l i d a t i o n process through d i s t u r b i n g patterned f i r i n g , the s t r e n g t h of the permanent memory should have remained constant over time.  Therefore t h i s f i n d i n g a l s o n e c e s s i t a t e s the f o r m u l a t i o n of an  a l t e r n a t i v e view of the e f f e c t of ECS on the c o n s o l i d a t i o n process. Two approaches to t h i s problem w i l l be considered here. One approach which has been taken to account f o r these two f i n d i n g s i s to p o s t u l a t e t h a t the memory t r a c e continues to change ' over a long p e r i o d and t h a t ECS produces a d i s t u r b a n c e which i n t e r f e r e s w i t h r e c a l l of the memory (Deutsch, 1971; Weiskrantz, 1966). Weiskrantz  (1966) assumes t h a t memory i n c r e a s e s over a prolonged  period of time, i n the sense of a c h i e v i n g a greater s i g n a l to n o i s e r a t i o ( t h i s time-dependent change i n the memory might be termed cons o l i d a t i o n although Weiskrantz does not r e f e r to i t as such).  He  suggests t h a t ECS does not d i s r u p t t h i s process (except when admini s t e r e d w i t h i n a few seconds of t r a i n i n g ) , but r a t h e r adds more n o i s e to the system.  This n o i s e impairs the r e c a l l of r e c e n t memories but  not o l d e r memories which have a g r e a t e r s i g n a l to n o i s e r a t i o . Weiskrantz's model can e x p l a i n the d i f f e r e n t g r a d i e n t s produced by  d i f f e r e n t i n t e n s i t i e s of ECS through assuming that the high intensity ECS produces more noise.  His model also predicts that ECS gradients  would only be temporary, since the signal to noise r a t i o continues to increase even after ECS i s administered, so that when the signal becomes s u f f i c i e n t l y strong, retention appears. There i s one major inadequacy of Weiskrantz's model.  I t implies  that the c r i t i c a l variable determining whether ECS w i l l impair performance i s the time between training and testing, and not the time between training and ECS. This follows because the two processes, noise produced by ECS and increasing strength of the memory signal, are assumed to be independent.  In other words, ECS i s not assumed to  d i r e c t l y affect the consolidation process at the time of administration; rather this process continues at i t s normal rate after ECS. Since the strength of the memory signal i s assumed to only depend on the time between training and testing, and since the noise produced by ECS i s independent of the time of ECS administration, presenting ECS between training and testing should have the same effect regardless of how long after training I t i s administered, so long as the time between  training and testing i s held constant.  However, con-  trary to this prediction, the time between training and ECS has been found to be much more important than the time between training and testing; i n f a c t , most experiments demonstrating ECS gradients keep the training-testing i n t e r v a l roughly constant.  For example, i n Ex-  periment 1 the series of ECSs impaired performance when administered at 1 or 24 hours but not 9 days after training even when the training-  69 testing i n t e r v a l was held constant at 11 days. Deutsch (1971) has proposed a similar model to Weiskrantz's although i t i s not simply intended to explain ECS gradients, but rather i s also concerned with the nature of memory storage.  Deutsch  assumes that memory i s stored i n the form of decreased synaptic r e sistance i n some cholinergic synaptic pathways. sistance  He assumes the r e -  continues to decrease for a number of days after t r a i n i n g  (again, this time-dependent change i n the memory i s not s p e c i f i c a l l y referred to as consolidation by Deutsch).  As evidence for this change  i n resistance, he has shown that anticholinesterase drugs impair performance of several tasks when administered ing, but not when administered  5 or more days after t r a i n -  1 or 3 days after t r a i n i n g . Deutsch  assumes that since the anticholinesterase drugs decrease the rate of breakdown of acetylcholine they w i l l f a c i l i t a t e synaptic  transmission.  ' Since synaptic resistance i s assumed to be high 1 or 3 days a f t e r t r a i n i n g , the synaptic f a c i l i t a t i o n w i l l f a c i l i t a t e (or at least not impair) r e c a l l .  However, at 5 or more days after t r a i n i n g , synaptic  resistance i s lower, and the synaptic f a c i l i t a t i o n produced by the drug w i l l produce too great a f a c i l i t a t i o n of synaptic resulting i n a blockage of r e c a l l .  transmission  As additional support for h i s  theory Deutsch has shown that anticholinergic drugs which impair synaptic transmission through blocking the effect of acetylcholine produce the opposite effects of anticholinesterase drugs, namely an impairment of performance when administered when administered  at 5 or more days.  at 1 or 3 days and no effect  In Deutsch's experiments the drugs are assumed to produce a temporary impairment of r e c a l l , and the treatment-testing i n t e r v a l i s kept constant at 24 hours, a time when acetylcholine or cholinesterase a c t i v i t y i s presumably s t i l l being affected by the injected substance. While Deutsch's data support the notion that memory continues to change over a period of days following t r a i n i n g , and also suggest that a change i n cholinergic synapses i s involved i n the memory, his model does not d i r e c t l y bear on the interpretation of gradients produced by other treatments such ECS.  If an attempt i s made to extend Deutsch's  model to other gradients, i t w i l l f a i l to adequately explain the f i n d ings, because Deutsch's model, l i k e Weiskrantz's, involves two  inde-  pendent processes; the drug i s not assumed to affect the change i n synaptic resistance at the time of administration. The second approach which has been taken to explain findings such as temporary gradients as w e l l as v a r i a b i l i t y i n the ECS  gradient  with ECS parameters i s to assume that ECS d i r e c t l y affects the consolidation process at the time of administration, and that the effect of ECS i s not necessarily to stop consolidation, but simply to slow i t s rate.  While several versions of this slowing hypothesis have been  presented (Albert, 1966; Cherkin, 1969; McGaugh & Dawson, 1971) a l l basically assume that consolidation may continue after ECS and that the degree to which consolidation continues depends on the ECS parameters.  The slowing hypothesis can be seen most clearly by contrast-  ing i t with the early view that ECS stopped consolidation.  When ECS  i s assumed to stop consolidation, the amount of memory present at  71  t e s t i n g would j u s t correspond t o the amount already c o n s o l i d a t e d when ECS was administered.  According  to the slowing h y p o t h e s i s , some mem-  ory would a l s o be c o n s o l i d a t e d a f t e r ECS a d m i n i s t r a t i o n .  Therefore,  at t e s t i n g the animal would have a v a i l a b l e the amount of memory cons o l i d a t e d before ECS as w e l l as the amount of memory c o n s o l i d a t e d a f t e r ECS. A s l o w i n g hypothesis  can e x p l a i n temporary g r a d i e n t s s i n c e i n  some cases s u f f i c i e n t c o n s o l i d a t i o n may continue f o l l o w i n g ECS to produce increased r e t e n t i o n when t e s t e d at longer times a f t e r t r a i n i n g than when t e s t e d soon a f t e r t r a i n i n g .  I t can a l s o e x p l a i n the v a r i -  a b i l i t y i n the l e n g t h of ECS g r a d i e n t s w i t h ECS parameters s i n c e a weaker ECS treatment might only s l i g h t l y r e t a r d c o n s o l i d a t i o n so t h a t a s u b s t a n t i a l amount of memory would be c o n s o l i d a t e d a f t e r ECS.  A  stronger ECS treatment on the other hand would slow c o n s o l i d a t i o n t o ' a greater degree, so that l i t t l e memory would be c o n s o l i d a t e d a f t e r 'ECS and consequently,  r e t e n t i o n would be poorer.  Mah, A l b e r t , and Jamieson (1972) have r e c e n t l y provided f o r a slowing hypothesis.  support  They found that a s i n g l e ECS given 5 min-  utes a f t e r p a s s i v e avoidance t r a i n i n g produced only a s l i g h t i m p a i r ment.  However, when a second ECS was presented  at 1 or 2 but not: 3  hours a f t e r a f i r s t ECS a t 5 minutes an a d d i t i o n a l d e f i c i t was observed.  The time-dependent e f f e c t of the second ECS appears to r e f l e c t  a d i s t u r b a n c e of c o n s o l i d a t i o n , i n d i c a t i n g that c o n s o l i d a t i o n was cont i n u i n g f o l l o w i n g the f i r s t ECS. The slowing hypothesis does not s u f f e r from the problem of models  72 such as Weiskrantz's (1966), since the effect of ECS i s assumed to be d i r e c t l y on the consolidation process.  Because ECS i s assumed to af-  fect consolidation at the time of administration, the training-ECS i n t e r v a l should be a more important determinant of the effect of ECS than the t r a i n i n g - t e s t i n g i n t e r v a l , a prediction consistent with most available evidence.  One slight, d i f f i c u l t y with the slowing  hypothesis  is that some authors (e.g., McGaugh & Dawson, 1971) interpret i t as predicting that consolidation would eventually reach completion i n a l l groups regardless of the training-ECS i n t e r v a l .  While this prediction  does not necessarily follow (for example, i f slowed s u f f i c i e n t l y no further consolidation might take place), several modifications of the slowing hypothesis can eliminate this interpretation. For example, McGaugh and Dawson (1971) postulate that ECS affects a short term memory stage, and the amount of short term memory determines the l e v e l that long term memory eventually reaches.  Another modification which  eliminates this interpretation would be to assume that ECS blocked some of the memory outright, and that only part of i t continued to consolidate.  Nevertheless, some form of a slowing hypothesis appears  to be the best explanation for the effects of ECS on the consolidation process. Clearly, a revised view of the consolidation process i s required. Rather than simply involving the formation of a permanent memory from neural f i r i n g patterns, consolidation must involve a gradual change i n the stored representation of the memory which may continue for at least several days after training.  Instead of being stopped by ECS, this  process may be slowed  to v a r y i n g degrees by d i f f e r e n t ECS treatments.  However, two major questions a r e s t i l l unanswered.  F i r s t , does con-  s o l i d a t i o n i n a t l e a s t some cases continue i n d e f i n i t e l y , so t h a t the memory never reaches a permanent s t a t e ?  Second, i s c o n s o l i d a t i o n i n  some cases completed more q u i c k l y ( w i t h i n a few minutes or hours) than i n other cases, as i s suggested by the r e s u l t s of Experiment 3?  Fur-  ther r e s e a r c h should provide answers to these questions as w e l l as the more b a s i c q u e s t i o n of the nature of the mechanism which underly the storage of i n f o r m a t i o n i n the b r a i n .  74  CONCLUSIONS  A series of f i v e ECSs produced greater impairment of a learned passive avoidance response when spaced 1 minute apart than when spaced 5 seconds apart or when presented i n one continuous burst.  In a l l  three cases the impairment was time-dependent; the length of the gradient varying from less than 1 hour (single ECS) to between 2 and 9 days (five ECSs spaced 1 minute apart).  The impairment produced by  the f i v e ECSs spaced 1 minute apart was permanent over 11 days, and was not attenuated when the ECSs were presented while the animals were anesthetized with ether or sodium pentobarbital, both of which blocked the convulsion normally produced by ECS. This long gradient does not appear to be q u a l i t a t i v e l y d i f f e r e n t from those found with a single ECS, and because of i t s greater length, probably r e f l e c t s a greater disturbance of the same process response for single ECS gradients. The most l i k e l y explanation for this process i s a time-dependent change i n the memory (consolidation). Therefore, i n this passive avoidance task the memory consolidation process appears to continue for at least several days. In a one t r i a l appetitive task, the f i v e ECSs spaced 1 minute apart did not produce a longer gradient than a single ECS. This f i n d ing might indicate that the consolidation processes i n the two tasks are q u a l i t a t i v e l y different and are d i f f e r e n t i a l l y disturbed by ECS, or that the consolidation process i s completed more quickly i n the appetitive task.  7.5  REFERENCES  A l b e r t , D. J . 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D i f f e r e n t temporal g r a d i e n t s of retrograde amnesia produced by carbon d i o x i d e anesthesia and e l e c t r o c o n v u l s i v e shock. J o u r n a l of Comparative and P h y s i o l o g i c a l Psychology, 1969, 69., 141-149. Pearlman, C. A. J r . , Sharpless, S. K., & J a r v i k , M. E. Retrograde amnesia produced by anestheic and convulsant agents. Journal of Comparative and P h y s i o l o g i c a l Psychology, 1961, _54, 109-112.  81 Pfingst, B. E., & King, R. A. Effects of posttraining electroconvulsive shock on retention-test performance involving choice. Journal of Comparative and Physiological Psychology, 1969, 68, 645-649. P i n e l , J. P. J. A short gradient of ECS-produced amnesia i n a onet r i a l appetitive learning s i t u a t i o n . Journal of Comparative and Physiological Psychology, 1969, .68, 650-655. P i n e l , J. P. J . Two types of ECS-produced disruption of o n e - t r i a l training i n the r a t . Journal of Comparative and Physiological Psychology, 1970, J72, 272-277. P i n e l , J. P. J . , & Cooper, R. M. The relationship between incubation and ECS gradient effects. Psychonomic Science, 1966, _6, 125126. Posluns, D., & Vanderwolf, C. H. Amnesia and d i s i n h i b i t o r y effects of electroconvulsive shock i n the r a t . Journal of Comparative and Physiological Psychology, 1970, 73, 291-306. Quartermain, D., Paolino, R. M., & M i l l e r , N. E. A b r i e f temporal gradient of retrograde amnesia independent of s i t u a t i o n a l change. Science, 1965, 149, 1116-1118. Ray, 0. S., & Barrett, R. J . Disruptive effects of electroconvulsive shock as a function of current l e v e l and mode of delivery. Journal of Comparative and Physiological Psychology, 1969, 67, 110-116. Ray, 0. S., & Bivens, L. W. Reinforcement magnitude as a determinant of performance decrement after electroconvulsive shock. Science, 1968, 160, 330-332. R i c c i o , D. C., Hodges, L. A., & Randal, P. K. Retrograde amnesia produced by hypothermia i n r a t s . Journal of Comparative and Physiological Psychology, 1968, j56, 618-622. Robbins, M. J . , & Meyer, D. R. Motivational control of retrograde amnesia. Journal of Experimental Psychology, 1970, .84, 220225. R o b u s t e l l i , F., Geller, A., & Jarvik, M. E. Temporal gradient of 23 hours with electroconvulsive shock and i t s implications. Communications i n Behavioral Biology, 1969, .4, 79-84. Russell, W. R., & Nathan, P. W. .69, 280-300.  Traumatic, amnesia.  Brain, 1946,  S c h i l l e r , A. M. , & Chorover, S. L. Short-term amnesic effect of electroconvulsive shock i n a o n e - t r i a l maze learning paradigm. Neuropsychologia, 1967, _5, 155-163. Schneider, A. M., & Sherman, W. Amnesia: a function of the temporal r e l a t i o n of footshock to electroconvulsive shock. Science, 1968, 159, 219-221.  Spevack, A. A., & Suboski, M. D. Retrograde effects of electroconvulsive shock on learned responses. Psychological B u l l e t i n , 1969, 72, 66-76.  Stephens, G. J . , & McGaugh, J. L. Retrograde amnesia: effects of p e r i o d i c i t y and degree of training. Communications i n Behavi o r a l Biology, 1968, 1, 267-275. S t i l l e , G., & Sayers, A. Motor convulsions and EEG during maximal electroshock i n the r a t . International Journal of Neuropharmacology, 1967, j>, 169-174. Suboski, M. D., Spevack, A. A., L i t n e r , J . , & Beaumaster, E. Effects of ECS following o n e - t r i a l discriminated avoidance conditioning Neuropsychologia, 1969, 7_, 67-78. Tenen, S. S. Retrograde amnesia from electroconvulsive shock i n a o n e - t r i a l appetitive learning task. Science, 1965, 148, 12481250 (a). * Tenen. S. S. Retrograde amnesia.  Science, 1965, 149, 1521 (b).  •Thompson, R., & Pennington, D. F. Memory decrement produced by ECS as a function of d i s t r i b u t i o n i n o r i g i n a l learning. Journal of Comparative and Physiological Psychology, 1957, J50, 401-404. Toman, J. E. P., Swinyard, E. A., & Goodman, L. S. Properties of maximal seizures and their a l t e r a t i o n by anticonvulsant drugs and other agents. Journal of Neurophysiology, 1946, 9_, 231239.  Weiskrantz, L. Experimental studies of amnesia. In C. W. M. Whitty and 0. L. Zangwill (Eds.), Amnesia. London: Butterworth & Co. 1966, 1-35.  Weissman, A. Effect of electroconvulsive shock intensity and seizure pattern on retrograde amnesia i n rats. Journal of Comparative and Physiological Psychology, 1963, 5_6, 806-810. Weissman, A. Effect of anticonvulsant drugs on electroconvulsive shock-induced retrograde amnesia. Archives Internationales de Pharmacodynamie et de Therapie, 1965, 154, 122-131.  83 Weiner, N. I. Electroconvulsive shock induced impairment and enhancement of a learned escape response. Physiology and Behavior, 1970, 5, 971-974. Williams, G. J . The e f f e c t of electroconvulsive shock on an i n strumental conditioned emotional response ( " c o n f l i c t " ) . Journal of Comparative and Physiological Psychology, 1961, 54, 633-637. Williams, G. J . The effect of varying the i n t e r v a l between c o n f l i c t training and electroconvulsive shock on an instrumental conditioned emotional response. Journal of Comparative and Physiol o g i c a l Psychology, 1963, _56, 129-131. Zinkin, S., & M i l l e r , A. J . Recovery of memory after amnesia induced by ECS. Science, 1967, 155, 102-103. Zornetzer, S. R, & McGaugh, J. L. Effects of f r o n t a l brain electroshock stimulation on EEG a c t i v i t y and memory i n r a t s : r e l a tionship to ECS-produced retrograde amnesia. Journal of Neurobiology, 1970, 1, 379-394. Zubin, J , & Berrera, S. E. Effect of e l e c t r i c convulsive therapy on memory. Proceedings of the Society for Experimental Biology and Medicine, 1941, 48, 596- 597.  84  APPENDICES  Appendix A B C  Page  A d d i t i o n a l S t a t i s t i c a l Analyses on Data from Experiment 1  85  A d d i t i o n a l S t a t i s t i c a l Analyses on Data from Experiment 2  88  E l e c t r i c a l Recordings Under Ether and Sodium Pentobarbital Anesthesia  90  85  APPENDIX A  A d d i t i o n a l S t a t i s t i c a l Analyses  1.  Data f o r experimental  Type o f ECS 5 ECSs s p a c e d 1 minute apart  5 ECSs s p a c e d 5 sec. apart  1 ECS, 2.5 s e c . duration  on D a t a From E x p e r i m e n t 1  groups  Time o f ECS  N  Median  Range  1.6  immed.  8  2.2  -  1 hr.  7  21.3  2 .3 - 23.6  24 h r s .  7  28.3  4 .0 - 60.0  48 h r s .  11  36.0  9 .0 - 60.0  9 days  8  59.3  31 .6 - 60.0  immed.  5  2.3  1 hr.  7  39.6  19 .0 - 60.0  24 h r s .  8  60.0  33 .6 - 60.0  immed.  5  3.3  1 hr.  7  51.3  2 .0 - 60.0  24 h r s .  6  57.8  31 .6 - 60.0  9 days  7  60.0  42 .3 - 60.0  2 .0 -  2 .3 -  3.0  2.6  3. 6  Appendix A (continued). 2.  Comparison between ECS d e l a y s f o r each ECS c o n d i t i o n . A l l analyses a r e done w i t h H a l p e r i n ' s (1960) e x t e n s i o n of the Mann-Whitney t e s t .  P r o b a b i l i t i e s a r e o n e - t a i l e d s i n c e the  longer ECS delays were not expected to produce greater impairments than the s h o r t e r d e l a y s .  5 ECSs 1 minute apart Immed. 1 hr.  1 hr.  24 h r s ,  .01  24 h r s .  .001  n. s.  48 hrs.  .001  .05  n. s.  .001  .001  .02  9 days  5 ECSs 5 seconds apart Immed. 1 hr.  .001  24 hrs.  .001  1 hr.  .02  1 ECS, 2.5 seconds d u r a t i o n Immed.  1 hr.  1 hr.  .001  24 hrs.  .001  n. s.  9 days  .001  n. s.  24 h r s  n.s.  87  Appendix A ( c o n t i n u e d ) . 3.  Comparisons between ECS treatments  f o r each ECS delay. A l l  analyses a r e done w i t h H a l p e r i n ' s (1960) e x t e n s i o n of the Mann-Whitney t e s t .  P r o b a b i l i t i e s a r e o n e - t a i l e d s i n c e the  g r e a t e r spacings were expected to produce g r e a t e r impairments.  Immediate ECS 1 ECS, 2.5 sec. d u r a t i o n 5 ECSs 5 sec. apart  .01  5 ECSs 1 min. apart  .02  5 ECSs 5 sec. apart  n.s.  1 hour ECS 1 ECS, 2.5 sec. d u r a t i o n 5 ECSs 5 sec. apart  .025  5 ECSs 1 min. apart  .001  5 ECSs 5 sec. apart  .02  24 hour ECS 1 ECS, 2.5 sec. d u r a t i o n 5 ECSs 5 sec. apart  n.s.  5 ECSs 1 min. apatt  .03  9 day ECS 1 ECS, 2.5 sec. d u r a t i o n 5 ECSs 1 min. apart  n.s.  5 ECSs 5 sec. apart  .01  APPENDIX B  A d d i t i o n a l S t a t i s t i c a l Analyses on Data from Experiment 2  Data f o r groups r e c e i v i n g 5 ECSs spaced 1 Drug Ether  Sodium Pentobarbital  Time of ECS  N  Median  1 hr.  6  11.5  1.6 - 60,0  24 h r s .  10  21.6  5.3 - 60.0  9 days  10  60.0  42.6 - 60.0  1 hr.  7  3.3  2.0 - 15.6  24 h r s .  9  11.3  1.6 - 60.0  9 days  6  54.8  25.6 - 60.0  Range  Appendix B (continued).  2.  Comparisons between ECS delays f o r each drug c o n d i t i o n . A l l analyses a r e done w i t h H a l p e r i n ' s (1960) e x t e n s i o n of the Mann-Whitney t e s t .  P r o b a b i l i t i e s are o n e - t a i l e d s i n c e the  longer ECS delays were not expected to produce g r e a t e r impairments than the s h o r t e r d e l a y s .  5 ECSs 1 minute apart under ether 1 hour 24 hours  n.s.  9 days  .01  24 hours  .01  5 ECSs 1 minute apart under sodium p e n t o b a r b i t a l 1 hour 24 hours  n.s.  9 days  .001  24 hours  .05  90  APPENDIX C  E l e c t r i c a l Recordings Under Ether and Sodium Pentobarbital Anesthesia  The r e c o r d i n g s presented here were obtained i n a p r e l i m i n a r y investigation;  these animals d i d not undergo t r a i n i n g .  L e v e l s of  a n e s t h e s i a a r e the same as those used i n Experiment 2. The r e c o r d i n g s were taken from a b i p o l a r e l e c t r o d e c o n s i s t i n g of t w i s t e d s t a i n l e s s s t e e l w i r e s , i n s u l a t e d except f o r 0.5 mm from the t i p , w i t h a 1.0 mm t i p s e p a r a t i o n . The e l e c t r o d e was aimed a t the c o r t e x 2.0 mm a n t e r i o r to bregma, 2.0 mm l a t e r a l t o the s a g g i t a l s u t u r e and 1.0 mm below the d u r a l s u r f a c e , and was implanted along w i t h ECS screw e l e c t r o d e s i d e n t i c a l to those used i n Experiments 1, 2, and 3.  A l l the r e c o r d i n g s presented here a r e from animals i n which  the e l e c t r o d e s were confirmed h i s t o l o g i c a l l y , to be i n the c o r t e x . Recordings were taken about a week a f t e r surgery.  Seizure d i s -  charge was recorded on an EEG channel of a Grass Model 7 polygraph. During passage of the ECS c u r r e n t , the polygraph leads were shorted to ground, and immediately a f t e r c u r r e n t o f f s e t were switched back to the animal.  Two to three seconds were l o s t to " b l o c k i n g " .  Recordings  were taken w i t h a time constant of 0.3, c h a r t speed of 2.5 mm per second, and s e n s i t i v i t y of 150 m i c r o v o l t s per cm. I n both F i g u r e 1 and F i g u r e 2 the r e c o r d i n g s from 10 d i f f e r e n t  91 Appendix C ( c o n t i n u e d ) . animals a r e presented.  The f i r s t segment s t a r t s w i t h the onset of the  c u r r e n t w h i l e the animal i s unanesthetized.  The f i r s t few seconds of  the records c o n t a i n s t i m u l u s a r t i f a c t s i n d i c a t i n g ECS onset and o f f s e t (the f i r s t two s p i k e s ) and the s w i t c h i n g of the r e c o r d i n g leads back to the animal from ground ( t h i r d s p i k e ) . a r e c o r d i n g taken 3 minutes a f t e r the ECS.  The second segment i s  The t h i r d segment s t a r t s  w i t h onset of an ECS g i v e n the f o l l o w i n g day w h i l e the animal was a n e s t h e t i z e d w i t h sodium p e n t o b a r b i t a l (Figure 1) or ether ( F i g u r e 2 ) . Again the three s t i m u l u s a r t i f a c t s can be seen a t the beginning of each r e c o r d .  The l a s t segment i s taken s h o r t l y ( u s u a l l y 10-30 seconds)  before ECS, i . e . , w h i l e the animal i s a n e s t h e t i z e d . The unanesthetized h i g h amplitude seconds.  (normal) s e i z u r e d i s c h a r g e was t y p i c a l l y of  (300-500 m i c r o v o l t s ) and l a s t e d between 15 and 18  The frequency was h i g h l y v a r i a b l e between animals,  although  i t t y p i c a l l y slowed toward the end of the s e i z u r e to 2 or 3 per s e cond.  I n some cases a few h i g h amplitude  s p i k e s appeared a f t e r the  s e i z u r e discharge had ended (animals 1, 2, 6, 7, 15). These may have been movement a r t i f a c t s .  I n some r e c o r d s , the post s e i z u r e d e p r e s s i o n  i s masked by r e s p i r a t i o n a r t i f a c t (1, 2, 3, 5, 10, 11, 12, 13, 15, 16, 19, 20). The s e i z u r e discharge under sodium p e n t o b a r b i t a l anesthesia was g r e a t l y attenuated  or absent.  I n no case d i d the s e i z u r e discharge  continue f o r longer than 12 seconds, nor was the amplitude higher than 75 m i c r o v o l t s (the l a r g e s p i k e i n record 8 was probably an a r t i f a c t ) .  Appendix C (continued). The post ECS d e p r e s s i o n i s very marked (the lowered p i r a t i o n caused by the a n e s t h e s i a decreases  i n t e n s i t y of r e s -  the magnitude of a r t i f a c t ) ,  The d e p r e s s i o n i s not an e f f e c t of the a n e s t h e s i a i t s e l f s i n c e the pre ECS r e c o r d ( l a s t column F i g u r e 1) t y p i c a l l y shows h i g h amplitude vity.  acti-  I t seems c l e a r that the c o n c e n t r a t i o n of sodium p e n t o b a r b i t a l  used here g r e a t l y attenuates s e i z u r e d i s c h a r g e , although the p e r i o d of post s e i z u r e d e p r e s s i o n i s s t i l l  present.  The r e c o r d i n g s under ether a n e s t h e s i a ( F i g u r e 2) are not as consistent. two animals  Two  animals  (11, 16) showed almost no s e i z u r e d i s c h a r g e ;  (12, 19) showed attenuated s e i z u r e d i s c h a r g e , and the other  s i x seemed to show a b r i e f e r p e r i o d of h i g h frequency a c t i v i t y normal, f o l l o w e d by a long s e r i e s of low frequency about 1 1/2 per s e c ) .  than  spikes (usually  This p e r i o d of low frequency s p i k i n g i s not  seen i n any of the unanesthetized r e c o r d i n g s (although 3 approximates i t ) , and i n some cases  (11, 14, 15) continues f o r longer than unan-  esthetized seizure discharge.  Two  c o n c l u s i o n s can be drawn about the  e f f e c t of ether anesthesia on s e i z u r e d i s c h a r g e :  f i r s t , i n most cases  the s e i z u r e d i s c h a r g e i s not b l o c k e d , and second, the p a t t e r n of s e i z u r e d i s c h a r g e under ether a n e s t h e s i a i s d i f f e r e n t from the unanesthetized pattern.  Figure 1.  Seizure Discharge f o r 10 Rats Receiving ECS While Unanesthetized and Later Under Sodium P e n t o b a r b i t a l Anesthesia.  F i g u r e 2.  Seizure Discharge f o r 10 Rats Receiving ECS While Unanesthetized and Later Under Ether Anesthesia.  

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