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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS009904-17
Application #
3394086
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1976-09-01
Project End
1992-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
17
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Arts and Sciences
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269
Shih, Evelyn K; Sekerková, Gabriella; Ohtsuki, Gen et al. (2015) The Spontaneous Ataxic Mouse Mutant Tippy is Characterized by a Novel Purkinje Cell Morphogenesis and Degeneration Phenotype. Cerebellum 14:292-307
Lee, Sun Kyong; Sillitoe, Roy V; Silva, Coralie et al. (2015) ?-Synuclein Expression in the Mouse Cerebellum Is Restricted to VGluT1 Excitatory Terminals and Is Enriched in Unipolar Brush Cells. Cerebellum 14:516-27
Sekerková, Gabriella; Watanabe, Masahiko; Martina, Marco et al. (2014) Differential distribution of phospholipase C beta isoforms and diaglycerol kinase-beta in rodents cerebella corroborates the division of unipolar brush cells into two major subtypes. Brain Struct Funct 219:719-49
Sekerková, Gabriella; Kim, Jin-Ah; Nigro, Maximiliano J et al. (2013) Early onset of ataxia in moonwalker mice is accompanied by complete ablation of type II unipolar brush cells and Purkinje cell dysfunction. J Neurosci 33:19689-94
Perge, Janos A; Niven, Jeremy E; Mugnaini, Enrico et al. (2012) Why do axons differ in caliber? J Neurosci 32:626-38
Kim, Jin-Ah; Sekerkova, Gabriella; Mugnaini, Enrico et al. (2012) Electrophysiological, morphological, and topological properties of two histochemically distinct subpopulations of cerebellar unipolar brush cells. Cerebellum 11:1012-25
Rousseau, Charly V; Dugue, Guillaume P; Dumoulin, Andrea et al. (2012) Mixed inhibitory synaptic balance correlates with glutamatergic synaptic phenotype in cerebellar unipolar brush cells. J Neurosci 32:4632-44
Mugnaini, Enrico; Sekerkova, Gabriella; Martina, Marco (2011) The unipolar brush cell: a remarkable neuron finally receiving deserved attention. Brain Res Rev 66:220-45
Nunzi, M G; Mugnaini, E (2009) Aspects of the neuroendocrine cerebellum: expression of secretogranin II, chromogranin A and chromogranin B in mouse cerebellar unipolar brush cells. Neuroscience 162:673-87
Russo, Marco J; Yau, Hau-Jie; Nunzi, Maria-Grazia et al. (2008) Dynamic metabotropic control of intrinsic firing in cerebellar unipolar brush cells. J Neurophysiol 100:3351-60

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