Open Collections

Studies on the induction of short- and long-term synaptic potentiation in the hippocampus

University of British Columbia

High frequency repetitive stimulation of an excitatory input in the hippocampus results in a post-tetanic potentiation (PTP) of short duration (about 3 min) that can be followed by a long-term synaptic potentiation (LTP) of the same excitatory input (Schwartzkroin and Wester, 1975; Andersen et al., 1977). It has been reported that this tetanus-induced LTP cannot be elicited in a Ca²⁺-free medium and is therefore a Ca²⁺-dependent process (Dunwiddie et al., 1978; Dunwiddie and Lynch, 1979; Wigstrӧm et al., 1979). Whether the induction of LTP is directly dependent upon Ca²⁺, or whether, Ca²⁺ is required because synaptic transmission is needed to initiate certain postsynaptic process(es) (a postsynaptic depolarization, for instance) leading to LTP, is unknown. Recent studies from this laboratory showed that both short-term potentiation (STP; with a duration resembling PTP) and LTP can be associatively induced if activation of a test input co-occured with either a tetanic stimulation of separate excitatory inputs or a sufficient depolarization of the postsynaptic neurone (Sastry et al., 1985). In this study, experiments were performed to investigate (1) whether associative STP could be induced when activation of the test input preceded or followed the onset of the conditioning train and (2) whether LTP could be induced in the absence of Ca²⁺ in the extracellular medium if sufficient depolarizations of the presynaptic terminals and postsynaptic neurones were provided. All experiments were performed using the transversely sectioned hippocampal slice preparation. Test stimuli were delivered via an electrode located in the stratum radiatum while the conditioning tetani (100 Hz, 10 pulses per train) were delivered via another electrode located in the recorded from the apical dendritic area of CA₁ neurones. After the initial control stimulation period, 5 conditioning tetani were given at a frequency of 0.2 Hz. The test stimuli either preceded (-) or followed ( + ) the onset of each conditioning train by 0 to 100 ms. When the test stimulus followed the onset of each conditioning train, there was significant STP of the test EPSP up to a conditioning-test interval of +80 ms. When the test stimulus preceded the onset of each conditioning train, there was significant STP of the test EPSP up to a conditioning-test interval of -50 ms. Conditioning tetani that were given without co-activation of the test input resulted in a subsequent depression of the test EPSP. It is suggested that either the test or the conditioning input can initiate some postsynaptic process(es) which can in turn affect the activated presynaptic terminals to increase transmitter release or alter the subsynaptic dendritic properties. For studying the possibility of the induction of LTP in the absence of Ca²⁺ in the extracellular medium, population EPSPs were recorded from apical dendritic area of CA₁ neurones in response to stratum radiatum stimulation. After the control stimulation period, slices were exposed either to Ca²⁺-containing or Ca²⁺-free (with Mn²⁺ and Mg²⁺ replacing Ca²⁺) medium, with the concentration of KC1 at 10 to 80 mM. Long-term potentiation of the population EPSPs was observed following the exposure to high K⁺ in Ca²⁺-free media. Following a brief period of potentiation initially, population EPSPs often exhibited a tendency toward depression after exposure to high K⁺ in Ca²⁺-containing media. LTP induced by high K⁺ in Ca²⁺-free medium could also be observed when a fixed number of axons were being activated, indicating that a recruitment of presynaptic fibres cannot entirely account for the potentiation. LTP of the depolarizing commands were paired with activation of the stratum radiatum while the slices were exposed to Ca²⁺ -free medium (normal concentration of KC1). These results suggest that extracellular Ca²⁺, synaptic transmission and thus subsynaptic receptor activation are not necessary for the induction of LTP as long as sufficient depolarizations of the presynaptic terminals and postsynaptic neurones are provided.

Text

2010-07-16

For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

http://hdl.handle.net/2429/26497

Pharmacology and Therapeutics

University of British Columbia

UBCV

DSpace