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POTENTIATION OF INHIBITION WITH PERFORANT PATH KINDLING: AN NMDA-DEPENDENT PROCESS
Citation:
Gilbert, M. POTENTIATION OF INHIBITION WITH PERFORANT PATH KINDLING: AN NMDA-DEPENDENT PROCESS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-91/322.
Description:
Kindling produces a long lasting enhancement of excitatory and inhibitory neurotransmission. Both long-term potentiation and kindling-induced potentiation of hippocampal excitatory neurotransmission are suppressed by N-methyl-d-aspartate (NMDA) antagonists. We have previously reported prolonged after discharges (AD) in perforant path kindled animals treated with the NMDA antagonist, MK-801, despite a retardation in the development of kindling. In the present study the potentiation of excitation and inhibition was assessed during perforant path kindling when NMDA channels were blocked with MK-801. Paired pulse (PP) inhibition was monitored before and during kindling development. MK-801 delivered prior to perforant path stimulation increased AD thresholds and delayed kindling development. Potentiation of the excitatory postsynaptic potential (EPSP) and of PP inhibition measured 18-20 h after each drug administration/stimulation were suppressed in MK-801-treated animals. Paradoxically, AD durations were prolonged by MK-801. Longer AD durations could be accounted for by a higher incidence of secondary AD bouts in MK-801 relative to control animals. Development of potentiation of the early phase of paired pulse inhibition was delayed and the potentiation of the late phase of inhibition was completely blocked by MK-801. hus, some of the enhancement of inhibition seen with kindling is dependent upon NMDA neurotransmission. Suppression of this potentiated inhibition may account for prolonged focal ADs in the perforant path and dentate gyrus.