The projects proposed in this grant focus on the role of the cerebellum and the nuclei to which it projects in the acquisition and performance of two different types of motor tasks: volitional goal-directed movements and classically conditioned reflex responses. Currently the specific function performed by the cerebellum in the learning and subsequent execution of these behaviors is a very controversial issue. The proposed experiments are based on the general hypotheses that: (I) this structure plays a critical role in the learning of motor behaviors because the integration it performs is crucial to the acquisition process rather than because it serves as an important, possibly exclusive site for the required plastic changes, (2) the cerebellum plays a critical role in organizing and coordinating motor sequences required for the acquisition as well as the execution of complex movements, and (3) discrete subsystems of the cerebellar output projections are critically involved in the acquisition-and -performance of different conditioned reflexes. The first group of experiments will employ a volitional forelimb task in- which cats learn to move a manipulandum through templates consisting of two to four successive, straight segments. Experiments using multiple single unit recording techniques as well as the microinjection of the temporary activating agent, muscimol, will determine the extent to which the cerebellum is critical for the acquisition of this behavior and examine the differences in modulation of cerebellar nuclear neurons during the performance of specific movement segments when each is performed in different contexts. The second series of experiments will explore the cerebellum's role in another type of motor learning, the classical conditioning of withdrawal reflexes. These experiments will assess the localization of the critical regions within these structures required for the acquisition and performance of the classically conditioned nictitating membrane (eyeblink) reflex using a newly developed microinjection technique for administering extremely small-quantities of muscimol in discrete locations within the cerebellar nuclei. After determining the location of these sites, anterograde and retrograde tracers will be injected to determine precisely the organization of the substrates which mediate the behavioral effects of the nuclear inactivation. Based on the findings obtained in the morphological studies, multiple single unit recording experiments will be performed to examine the relation of impulse activity in specific brainstem nuclei to the time course of the acquisition of this conditioned reflex. Last, the action of specific regions of the cerebellar nuclei on two different conditioned withdrawal reflexes, the eyeblink reflex and the flexion withdrawal reflex of the forelimb, will be evaluated to test the hypothesis that the cerebellar efferent projections participating in the regulation of conditioned reflexes involving entirely different patterns of behavior and different regions of the body are distinct. The results also will address the concept that the integration performed by the cerebellum is important for the execution of both the conditioned (learned) and unconditioned (unlearned) reflexes.
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