This competitive renewal examines morphological and chemical phenotypes and other cellular properties of two populations of cerebellar neurons, the small neurons of the roof nuclei and the newly discovered unipolar brush cells of the cerebellar granular layer, which are presumably excitatory But utilize still undetermined neurotransmitter and neuropeptides. We proved that most of the small nuclear neurons project to the inferior olive, utilize the inhibitory neurotransmitter GABA, and are likely to control the synchronicity of climbing fiber firing. Structure-function data accumulated during the past budget period suggest that the unipolar brush cells produce powerful feed forward excitation of mossy fiber activity. The principal aims of this project are to characterize the small nucleo- olivary development and efferent connections of the unipolar brush cells. We will study the form and fine structure of the small cerebellar nuclei neurons with a battery of experimental methods, attempt to determine whether other subpopulations of these small neurons differ from the nucleo-olivary category, and analyze their plastic changes in mutant mice that lose their Purkinje cells. We will also study the cytoskeleton of the unipolar bush cells and the postsynaptic proteins situated at the giant synapse that receive from mossy fibers, explore the relations between ultrastructure and physiological characteristics of the two main forms of this synapse, continuous and fragmented, and probe the susceptibility of the cells to excitotoxic damage. The progenitors from which these cells originate will be identified in vivo and their developmental pattern analyzed in normal and mutant animals. Enriched and purified dissociated cultures of unipolar brush cells will be used to re-establish in vitro their synapses with mossy fibers and ascertain their cell-autonomous and cell-extrinsic properties. Data obtained from these studies will promote better understanding of the function of the cerebellar system in movement control and sensorimotor transformations.
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