This proposal is designed to further characterize the specific cerebellar GABAergic processes that appear critical for a form of simple associative learning namely, classical conditioning of the rabbit nictitating membrane response. Behavioral experiments, employing pharmacological microinfusion techniques, are formulated to test several hypotheses: (1) that pharmacological manipulation of GABAergic transmission, which has been shown to impair retention of conditioned responding, will also impair acquisition; and (2) that benzodiazepine agonists and antagonists, which are known to differentially modulate GABA A transmission, can enhance and impair acquisition, respectively. Implicit in this hypothesis is the notion that enhancement of GABAergic transmission at these sites will enhance acquisition of the CR. Furthermore, concurrent receptor analyses, employing quantitative autoradiographic techniques, will test the hypothesis that learning-related plasticity may occur at these GABAergic processes within specific cerebellar loci and, in part, be expressed as modifications in the GABA-receptor-ionophore-complex. These studies will determine: (1) potential changes in both receptor affinity and number for the GABA and benzodiazepine recognition sites; and (2) potential modification in the interaction between these recognition sites. Together, these investigations should contribute to our understanding of the neural substrates subserving simple associative learning and the interface of this process with cerebellar control of motor function. In addition, these results should broaden our understanding of disease processes, including those involved in disorders of learning and memory and in cerebellar degenerations, which affect the loci addressed in this proposal.
