Receptor blockade reveals a correspondence between hippocampal-dependent behavior and experience-dependent synaptic enhancement.

This study examined the involvement of N-methyl-D-aspartate receptors (NMDARs) in experience-dependent synaptic plasticity. Rats chronically received an NMDA receptor antagonist (AP5) or saline (SAL) and were exposed to individual cages (IC) or environmental enrichment (EC). AP5 impaired measures of hippocampal-dependent behavior and increased locomotor activity. Perforant path synaptic strength, measured in the in vitro hippocampal slice, was increased and long-term potentiation (LTP) was decreased for EC+SAL animals. The experience-dependent effects on synaptic function were inhibited by drug treatment. Measures of synaptic strength were correlated with hippocampal-dependent behavior and synaptic plasticity for EC animals. The results suggest a relationship between hippocampal-dependent behavior and experience-dependent modification of perforant path synaptic function through NMDAR activation.