Plasticity and variation of synaptic responses in hippocampus. Role of AMPA and NMDA receptors

Abstract: It is generally believed that synaptic plasticity in the central nervous system may underlie learning and memory as well as neuronal development. The most wellstudied examples of such synaptic plasticity are long-term potentiation (LTP) andlong-term depression (LTD). LTP is normally induced by high frequency (20-100 Hz)stimulation (HFS) and LTD by low frequency (1-10 Hz) stimulation (LFS). Thepresent study deals with a novel kind of synaptic plasticity induced by test frequency(¡« 0.1 Hz) stimulation (TFS). The involvement of AMPA and NMDA receptormediated responses was studied under different conditions.The experiments were carried out in hippocampal slices from 2-3 week oldSprague-Dawley rats. Extracellular recording or ¡°blind¡± whole-cell patch clamprecording technique were used to study a population of pyramidal cells or individualones in the CA1 area of hippocampus. A low Mg2+ perfusion solution was used toallow for expression of both AMPA and NMDA receptor mediated components of thefield excitatory postsynaptic potentials (EPSPs). Whole-cell patch clamp was used toexamine the variability of excitatory postsynaptic currents (EPSCs) mediated byAMPA and NMDA receptors at different holding potentials.The results showed that, under conditions of facilitated NMDAR activation, thedecay of LTP is an activity and NMDAR dependent process, and can be induced byTFS. TFS can also induce a potentiation and decay of synaptic responses underdifferent manipulations in a naive pathway. Both potentiation and decay are NMDARdependent processes. It was also shown that the decay was associated with equalrelative change of AMPA and NMDA components. Furthermore, the comparison wasmade between the TFS induced depression and LTD. LTP could be induced in thepresence of TFS induced depression but the degree of potentiation was inverselyrelated to the degree of depression. The depression was not significantly influencedby prior LTD but showed a partial interaction with LTD induced afterwards. Wholecellrecording showed that the variability of AMPA and NMDA EPSCs is basicallythe same under baseline conditions.The results suggest that TFS can modify and induce synaptic plasticity dependingon the history of synaptic activities and such synaptic plasticity has severalcharacteristic in common with LTD/LTP. A coupling between AMPA and NMDAreceptors with respect to their response variations under baseline conditions and to theresponse changes during LTD/LTP is also suggested.