LONG-TERM POTENTIATION IS ASSOCIATED WITH INCREASED [H-3] AMPA BINDING IN RAT HIPPOCAMPUS

The location and nature of the changes underlying long-term potentiation (LTP) remain controversial issues. In this study, we tested the possibility that changes in binding properties of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/quisqualate and N-methyl-D-aspartate (NMDA) subtype of glutamate receptors are associated with LTP. LTP was elicited in vivo by stimulation of the perforant pathway in anesthetized rats. One hour following stimulation the animals were sacrificed. We performed quantitative ligand binding autoradiography on frozen brain sections using [H-3]AMPA and [H-3]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([H-3]TCP) to label the AMPA/quisqualate and the NMDA receptors, respectively. No changes in [H-3]TCP binding were detected in any of the treatment groups. However, increases in [H-3]AMPA binding were observed only in animals that exhibited LTP. These increases were bilateral and present in several subfields of the hippocampus and cortical areas. Administration of the NMDA receptor antagonist, ketamine, prior to tetanic stimulation prevented both the increase in binding and the induction of LTP. These results suggest that changes in the characteristics of AMPA/quisqualate receptors are a biochemical correlate of LTP.