The proposed experiments will investigate the effects that a conditioned stimulus (CS) exerts on the behavioral responses and neuronal activity elicited by the unconditioned stimulus (US) during classical conditioning of the nictitating membrane (NM) response in rabbit. Behaviorally, at brief CS-US intervals (20-60 msec), a CS markedly inhibits the unconditioned NM response, whereas at longer intervals (greater than 100 msec), a CS produces strong facilitation of the unconditioned response. Physiologically, we have found that CSs modify US-elicited activity of Purkinje cells in the cerebellum and that the modifications are also dependent on the duration of the CS-US interval. A strong relationship between the ability of a CS to facilitate unconditioned NM responses and the ability of the CS to support the acquisition of overt conditioned responses (CRs) has been supported by both behavioral and pharmacological evidence. In that the behavioral and physiological effects of the CS on US-elicited activity are observed from the beginning of training and long before the appearance of overt CRs, the initial CS-US interactions may represent the early stages of CR acquisition. Investigation of these interactions offers the possibility of uncovering the antecedents of associative conditioning. In the proposed experiments we will use lesion, electrophysiological, and behavioral techniques to investigate US-elicited behavior prior to the appearance of conditioned responses.
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