Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus

The NMDA and AMPA receptors have been shown to play critical roles in various forms of synaptic plasticity (learning and memory, long-term potentiation). The present study investigated the involvement of these two receptors in a well-characterized classical conditioning paradigm. Following classical conditioning of the rabbit nictitating membrane the binding properties of these two subclasses of excitatory amino acid transmitter receptors were analyzed in dorsal hippocampi by quantitative autoradiography. [³H]TCP and [³H]AMPA were used to identify the NMDA and AMPA receptors, respectively. The binding of [³H]TCP to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of the conditioned and unconditioned stimuli resulted in increased [³H]AMPA binding to the AMPA receptor in several subfields of the hippocampus, while unpaired presentations had no significant effects. The increase in binding was due to an increased affinity of the low-affinity component of the AMPA receptor. The results support the hypothesis that changes in glutamate receptors participate in the synaptic plasticity involved in certain forms of learning.