INDUCTION OF LTP IN THE HIPPOCAMPUS NEEDS SYNAPTIC ACTIVATION OF GLUTAMATE METABOTROPIC RECEPTORS

UNDERSTANDING the mechanisms of long-term potentiation (LTP) should pr ovide insights into the molecular basis of learning and memory in vert ebrates. Ionotropic glutamate receptors play a central role in LTP; AM PA ha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors and NM DA (N-methyl-D-aspartate) receptors mediate synaptic responses that ar e enhanced in LTP and, in addition, NMDA receptors are necessary for t he induction of LTP in most pathways1. There is also circumstantial ev idence that metabotropic glutamate receptors (mGluRs) may be involved in LTP because the specific mGluR agonist aminocyclopentane dicarboxyl ate can augment tetanus-induced LTP2 and, under certain circumstances, can itself induce a slow-onset potentiation3,4. But the absence of an y effective mGluR antagonist has prevented the determination of whethe r mGluRs are involved in the induction of tetanus-induced LTP. We repo rt here that (RS)-alpha-methyl-4-carboxyphenylglycine is a specific mG luR antagonist in the hippocampus and have used this compound to exami ne the nature of the involvement of mGluRs in LTP. We show that synapt ic activation of mGluRs is necessary for the induction of both NMDA re ceptor-dependent and NMDA receptor-independent forms of LTP in the hip pocampus.