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Differential effects of calcium and tetanic stimulation frequencies on hippocampal synaptic potentiation and depression

University of British Columbia

In the hippocampus, tetanic stimulation of an input results in a long lasting potentiation (LLP) of synaptic transmission involving that input. While high frequency tetanic stimulations are preferred to elicit LLP, low frequency tetanus induces homosynaptic and heterosynaptic depressions. The present investigations were conducted to (1) analyse the characteristics of pulses in orthodromic and antidromic tetanic stimulations and relate them to post-tetanic changes in evoked potentials (2) determine if potentiation and depression co-occur and (3) determine whether an established LLP in one input is subsequently modified by the initiation of LLP in another input (to the same CAlb neurons) or whether LLP can be reversed by homosynaptic and heterosynaptic depressions and lastly (4) determine how interference or enhancements of calcium and potassium fluxes with pharmacological substances related to potentiation and depression. Experiments were conducted on transversely sectioned rat hippocampal slices. Evoked potentials in subfield CAlb were elicited with stimulations of CAlb axons, commissural (Com), or Schaffer collaterals (Sch). Sch terminal excitability was tested with a stimulating electrode placed in the Sch/CAlb synaptic regions. Recordings were made with microelectrodes positioned in the CAlb cell bodies and/or dendritic regions, and in field CA3. It was found that potentiation and depressions co-occur. Presynaptic volleys accompanied all tested tetanic trains. Similarly, antidromic trains discharged CAlb neurons continuously but did not cause LLP. Low frequency tetanic trains caused facilitated synchronous discharges of CAlb neurons during significant portions of these trains. In contrast, few if any syn- chronous discharges followed high frequency tetanus. Yet high frequency tetanus elicited LLP and low frequency tetanus caused homo- and heterosynaptic depressions. An established LLP could be masked but not reversed by homo- and heterosynaptic depressions but this LLP was not interrupted by subsequently induced LLP of a separate input. Iontophoretic L-glutamate on CAlb cell bodies caused depression which was more pronounced if a tetanus was evoked during L-glutamate ejections. The depressions to low frequency tetanus and L-glutamate were counteracted by verapamil. Lastly, barium and 4-aminopyridine potentiations were reversed with washing. Applications of these drugs did not alter Sch terminal excitability. Tetanus induced during the presence of 4-aminopyridine still elicited LLP. It is concluded that homo- and heterosynaptic depressions are partly due to the accumulation of calcium into the CAlb neurons. The magnitude of calcium entry into presynaptic and postsynaptic regions is governed by the tetanic frequencies evoked. The results are consistent with a presynaptic mediated LLP.

Text

2010-05-11

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http://hdl.handle.net/2429/24594

Pharmacology

University of British Columbia

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