This proposal is a neurophysiological study of the climbing fiber system's role in the cerebellar cortex and motor behavior. The global hypothesis underlying the grant is that the climbing fiber afferent system, possibly acting as an error signal, increases a Purkinje cell's responsiveness to mossy fiber input. The climbing fiber input to neighboring Purkinje cells is tightly correlated, resulting in an accentuation of the gain of a cerebellar cortical region. The altered Purkinje cell output from a cerebellar cortical region is hypothesized to modify motor behavior. Initial studies in acute cats will evaluate climbing fiber afferent modification of Purkinje cell responsiveness to mossy fiber input. Short and long term changes will be evaluated using analytical techniques designed to remove the simple spike signal from the background activity. These techniques will permit statistical evaluation of the changes in simple spike activity associated with climbing fiber afferent input. Using two models of behavior, locomotion in the premammillary cat and voluntary arm movements in the intact primate, the interaction between climbing fiber afferent input and Purkinje cell discharge will be evaluated. The evoked complex spike activity and associated changes in simple spike activity will be related to alterations in walking or limb movements. Statistical analyses are designed to evaluate the relationships between the complex spike discharge, simple spike activity and the movement kinematics. The inferior olive possesses an inherent tendency to oscillate. Acute cat studies will test whether the rhythmicity represents a brief, but stable limit cycle of a population of inferior olivary neurons. The resetting characteristics of spontaneous as well as evoked complex spike discharge will be evaluated and compared. In the primate movement studies the presence or absence of climbing fiber rhythmicity will be evaluated. Associated rhythmicity in the simple spike discharge, limb kinematics or EMG activity will be evaluated. Overall these studies will increase our understanding of the role of the climbing fiber afferent system in the cerebellar cortex and motor behavior.
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