Inhibitory conditioning is a central component of theoretical models of associative learning but its neural basis has not been fully elucidated. Conditioned inhibition is generally thought to be due to the development of an association between a conditioned stimulus (CS) and the omission of an unconditioned stimulus (US). The proposed project will initiate a research program to examine the neural mechanisms of inhibitory classical conditioning. The eyeblink conditioning preparation will be used in these experiments in order to compare the neural mechanisms of inhibitory conditioning with the previously identified neural mechanisms of excitatory conditioning. The experiments of Specific Aim 1 will investigate the role of the cerebellar cortex in conditioned inhibition using excitotoxic lesions, unit recording, and reversible inactivation. In the experiments of Specific Aim 2, pharmacological inactivation will be used to assess the roles of several possible sites within the neural circuitry underlying the acquisition and expression of excitatory eyeblink conditioning in the acquisition of conditioned inhibition. The experiments of Specific Aim 3 will determine whether conditioned inhibition involves neural systems that are distinct from the neural systems that mediate excitatory conditioning. The fundamental importance of inhibitory learning underscores the need to study its neural mechanisms. The proposed research project will provide important initial steps toward determining the neural mechanisms of inhibitory classical conditioning. A successful analysis of the neural mechanisms of inhibitory classical conditioning may lead to the application of this experimental approach to the study of excitatory and inhibitory processes that occur in other learning situations. The results of these studies may also lead to a better understanding of the functional pathology associated with various psychiatric disorders that involve deficits in behavioral inhibition.
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