The goal of this proposal is to investigate the spatial patterns of responses evoked by peripheral inputs to the cerebellar cortex. the intrinsic circuitry of the cerebellar cortex with its well defined geometry, as well as the spatial organizations which characterize the two main afferent systems are central to many theories of cerebellar function. A promising technique to study spatial patterns of activity in neuronal populations is optical recordings using voltage sensitive dyes and imaging processing techniques. Proposed are experiments to evaluate four specific aims concerning the patterns of responses evoked by peripheral inputs to the cerebellar cortex using optical imaging and voltage sensitive dyes. In the first specific aim, we propose to define the spatial characteristics of the responses evoked by peripheral inputs to the rat cerebellar cortex in vivo. Using electrical and natural stimulation of peripheral inputs, the patterns of optical response in a single folium will be imaged. The time course and depth dependency of the response patterns will be evaluated. Emphasis will be placed on correlating extracellular field recordings and single Purkinje cell activity with the optical responses. In the second specific aim, a series of experiments are proposed to dissect out several of the components in the optical response. These experiments include an evaluation of the contribution of presynaptic afferent activity to the optical response, the role of the intrinsic inhibitory circuit due to the GABAA receptor, and effects of golgi cell inhibition. In the third specific aim, studies are proposed to determine the relative contributions of mossy fiber and climbing fiber afferents to the spatial patterns of activity evoked by peripheral stimuli. Exploiting the long refractory period of inferior olivary neurons, the response patterns evoked by these two afferent systems will be dissociated. Additionally, the topographic relationships between the responses evoked by these two afferent systems will be mapped. The fourth specific aim is to determine the spatial component of any interaction between the climbing and mossy fiber afferent systems. These experiments will be based on an experimental paradigm in which either parallel fiber of mossy fiber inputs are imaged with and without activation of the contralateral inferior olive. These studies will permit an evaluation of how climbing fiber input modifies the spatial characteristics and amplitude of the response patterns evoked by either parallel fiber input or mossy fiber input.
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