Abstracts

Rationale: Excitatory synapses onto GABAergic interneurons of CA3 stratum radiatum are named type II or type I respectively if they express or lack Ca2+-permeable AMPA receptors. We have previously demonstrated that Ca2+-permeable AMPA receptors, activated at hyperpolarizing membrane potentials, are required for long-term depression (LTD) induced by high frequency bursts at type II synapses. Based on that and on the fact that synaptic NMDA receptors are widely expressed at excitatory synapses onto hippocampal interneurons, we tested whether activation of NMDA receptors, following epileptic-like burst stimulation, could induce long-term potentiation (LTP) at type II synapses. Methods: Whole-cell patch clamp recordings were obtained from interneurons in hippocampal slices prepared from juvenile rats. EPSCs evoked by electrical stimulation of CA3 pyramidal cells in the presence of 10 M bicuculline were monitored for 5 minutes at low frequency (0.16 Hz). Then, a high frequency stimulation consisting of epileptic-like bursts (3x100 Hz, 0.3s) was applied while the neuron was voltage clamped at a potential of V30 mV to activate synaptic NMDA receptors. Results: Synaptic potentiation of the EPCSs amplitude (198 + 20 %, n=4) occurred at 4 out of 6 type II synapses. In contrast, no significant change in EPSC amplitude was detected after burst stimulation at type I synapses (111 + 9 %, n=3). In addition, in two interneurons expressing type II synapses, loaded with 30 mM BAPTA, potentiation following high frequency stimulation was not observed. In most of the experiments a slow synaptic current blocked by 50-100 M D-APV was detected at + 40 mV, suggesting that NMDA receptors were expressed at both synapses. Conclusions:The present findings suggest a possible role of NMDA receptors, activated by tetanic depolarization, in inducing LTP at type II synapses. In combination with our previous demonstration of a Ca2+-permeable AMPA receptor dependent LTD requiring hyperpolarization, these results support the idea that type II synapses can differently decode information carried by high frequency bursts depending on the level of postsynaptic voltage. This work was supported by American Epilepsy Society (FL) and NIH.