This competitive Continuation Research Program will be centered on A) Comparison between microcircuits of cerebellum and dorsal cochlear nucleus (DCN) to define their differences and similarities, using normal, newborn and adult laboratory mammals and certain murine mutants; and B) Distribution and principles of organization of inhibitory GABAergic neurons in cerebellar and acoustic systems in particular, and in CNS in general. Specific studies will be: I. In the Acoustic System, presence in DCN cartwheel cells of cytological markers shared with Purkinje cells; possible DCN abnormalities in murine mutants with cerebellar defects; continued studies of cellular typology and synaptic connections in DCN (with emphasis on axonal plexus of stellate and cartwheel cells, the Golgi cells, organization of deep DCN layers, reciprocal connections between DCN and VCN, and sources of cochlear mossy fibers); inhibitory GABAergic neurons of the brain stem acoustic system, especially those that may be part of afferents descending to cochlear nuclei. II. In the Cerebellar System, a study of features and synaptic connections of small cerebello-olivary GABAergic projection neurons of deep nuclei and of other source cells of GABAergic inputs to inferior olive. III. In general Neurology and Methodology, and atlas of GABAergic elements in CNS; advancements of immunocytochemistry, intended to qualify co-existence of neuropeptides and traditional transmitters in individual acoustic and cerebellar neurons. A battery of procedures will be used, including Golgi/EM, axonal transport methods, light and electron microscopic immunocytochemistry, and computer-assisted morphometry. The proposed studies will help understand ontogenetic and evoluntionary development and plasticity of CNS neural procesing, and participation of GABAergic neurons in sensory-motor and communication disorders.
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