We demonstrate a form of long-term depression (LTD) in the perirhinal cortex that relies on interaction between different glutamate receptors. Group II metabotropic glutamate (mGlu) receptors facilitated group 1 mGlu receptor-mediated increases in intracellular calcium. This facilitation plus NMDA receptor activation may be necessary for induction of LTD at resting membrane potentials. However, depolarization enhanced NMDA receptor function and removed the requirement of synergy between group I and group II mGlu receptors: under these conditions, activation of only NMDA and group I mGlu receptors was required for LTD. Such glutamate receptor interactions potentially provide new rules for synaptic plasticity. These forms of LTD occur in the perirhinal cortex, where long-term decreases in neuronal responsiveness may mediate recognition memory.
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