SELECTIVE CHANGES IN AMPA RECEPTORS IN RABBIT CEREBELLUM FOLLOWING CLASSICAL-CONDITIONING OF THE EYELID-NICTITATING MEMBRANE RESPONSE

lpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) recepto rs are critically involved in several forms of synaptic plasticity pro posed to be neural substrates for learning and memory, e.g., long-term potentiation and long-term depression (LTD). The present study was de signed to determine changes in cerebellar AMPA receptors following cla ssical conditioning of the eyeblink-nictitating membrane response (NMR ) in the rabbit. Quantitative autoradiography was used to assess chang es in ligand binding properties of cerebellar AMPA receptors following NMR conditioning elicited by pairing electrical stimulation of the po ntine nuclei with an ah-puff to the eye. [H-3]AMPA and [H-3]-6-cyano-7 -nitroquinoxaline-2,3-dion (CNQX) binding were determined following pr eincubation of frozen-thawed brain tissue sections at 0 or 35 degrees C. With 0 degrees C preincubation, no significant differences in [H-3] AMPA binding to cerebellar AMPA receptors were seen between any of the experimental groups tested. In contrast, preincubation at 35 degrees C revealed significant decreases in [H-3]AMPA binding to the trained s ide of the cerebellar cortex resulting from paired presentations of th e conditioned and the unconditioned stimuli, while unpaired presentati ons of the stimuli resulted in no significant effect. With 35 degrees C preincubation, there were no significant differences in [H-3]CNQX bi nding between any of the experimental groups and no significant differ ences in [H-3]AMPA binding in the untrained side of the cerebellum. Th ese results indicate that NMR conditioning is associated with a select ive modification of AMPA-receptor properties in brain structures invol ved in the storage of the associative memory. Furthermore, they suppor t the hypothesis that cerebellar LTD, resulting from decreased synapti c efficacy at parallel fiber-Purkinje cell synapses mediated by a chan ge in AMPA-receptor properties, is a form of synaptic plasticity that supports this type of learning. (C) 1998 Published by Elsevier Science B,V. All rights reserved.