The long-term goal of research proposed in the present application is to delineate neuronal systems and processes involved in simple forms of learning and memory. More specifically, this research seeks to advance our understanding of the involvement of the cerebellum in a simple motor learning task, classical eyelid conditioning in rabbits. Three experiments are proposed that use anesthetized classical conditioning preparations. These preparations involve the pairing of brain microstimulation in place of peripheral conditioning stimuli and recording unit activity from brain stem nuclei known to be involved in generating conditioning responses in place of monitoring overt behavioral responses. The proposed experiments include: (1) An analysis of extracellular single unit cerebellar activity during and after conditioning, (2) Manipulations of the """"""""behavioral"""""""" training regimen used during the anesthetized conditioning, and (3) Intracellular recordings coupled with HRP labeling after conditioning. These experiments have been designed to explore similarities and differences in conditioning between awake and anesthetized rabbits, to provide information about changes in the activity of cerebellar neurons induced by the anesthetized conditioning procedures, and to provide some insight into the connectivity between cerebellar and brain stem neurons involved in the conditioning. The further development of this anesthetized conditioning preparation should facilitate the definition and study of cerebellar and brain stem circuits activated during this form of learning. Intracellular analyses of neuronal activity should provide initial information about cellular processes and synaptic mechanisms associated with classical eyelid conditioning. We anticipate that these mechanisms may be generalizable to other motor learning and memory situations and therefore advance our understanding of basic cerebellar and brainstem neuronal function. Results from these experiments should also prove useful for understanding loss of normal function associated with cerebellar pathologies caused by injury or disease. Moreover, advancing our knowledge of cellular and synaptic processes involved in simple motor learning and memory should prove useful for understanding more complex learning and memory processes and the cellular bases of learning impairments and memory loss associated with disease and injury.
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