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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS009904-28
Application #
2873124
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Spinella, Giovanna M
Project Start
1976-09-01
Project End
2001-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
28
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Evanston
State
IL
Country
United States
Zip Code
60201
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
Dino, M R; Mugnaini, E (2008) Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nucleus. Neuroscience 154:29-50

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