Associative nictitating membrane (NM), or eyeblink, conditioning in the rabbit will be used to examine alterations in the structural organization of the cerebellum and associated brainstem structures that occur as a result of learning. The substrates of learning are believed to be fundamental mechanisms of brain information storage that are involved in brain development, memory, recovery from brain damage, as well as in certain pathological conditions, perhaps including epileptogenesis. Associative conditioning involves the pairing of a conditioned stimulus (CS) tone with the delivery of an unconditioned stimulus (US) puff of air to the cornea of the eye over repeated trials such that a conditioned eyeblink response (CR) comes to be elicited by the tone alone. Comparison with rabbits that experience tones and airpuffs at random intervals allows identification of brain changes specific to associative learning and exclusion of brain changes brought about by exposure to the stimuli or emission of the motor response. In addition, as conditioning occurs unilaterally, a within-animal control exists for nonassociative responses to the conditioning process (e.g. stress [which is not particularly evident in the subjects], extraneous motor activity, other general metabolic changes induced by conditioning). Considerable research has elucidated brainstem and cerebellar structures that mediate the conditioning process. Prior data indicates that structural changes in Purkinje and probably stellate neurons occurs in the cerebellar (lobule HVI) hemisphere that mediates the conditioned response, while no structural effects are evident in animals receiving random stimulus presentation. The goal of this proposal is to discern the types of morphological changes at the cellular (neuronal) that occur both in cerebellar cortex and deep nuclei and in brainstem structures that carry input and output information that is critical to the acquisition and performance of the conditioned response. Other structures to be investigated are the dorsal accessory olive, source of US information, and the red nucleus, the primary post-cerebellar structure along the CR pathway. The methods to be employed include quantitative analysis of neurons impregnated by the Golgi techniques and unbiased stereological estimation of synaptic numerical change.
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