Intense research efforts over the past four decades have provided a wealth of information on the development, structure, and function of the cerebellum. Still there remain many outstanding issues on the role of the cerebellum in motor learning and its neuronal substrate, the spatial and temporal interactions between climbing and mossy fiber afferent systems, and the relations between neuronal activity and cerebellar blood flow. Also there remain many gaps in our understanding of the molecular events governing cerebellar neuronal development and on the specific glutamate receptor subtypes associated with the neural input to Purkinje cells. Obtaining answers to these questions is critical for defining the basic events underlying cerebellar development and functional organization and for obtaining insights into the mechanism leading to cerebellar dysfunction. This program project application builds upon the strong interactions and productive collaborations established among the investigators during the last funding period to continue to explore cerebellar gene expression, neuronal development, neurochemistry and function. The investigators use state-of-the-art molecular, cellular and system approaches to address hypothesis concerning: 1) the role of the CREB family of transcription factors system in Purkinje cell synaptic plasticity; 2) the interaction between cell cycle regulatory neuronal differentiation, 3) glutamate receptor subtypes associated with the molecular layer of the cerebellum and their involvement in nitric oxide production; 4) neural mechanisms mediating changes in cerebellar blood flow during normal cerebellar function; and 5) the spatial and temporal characteristics and interactions of the climbing and mossy fiber afferents. This Program Project offers a unique and highly integrated multi-disciplinary approach to continue to provide new information on fundamental aspects of cerebellar development, structure and function.
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