Neurotransmitter receptors for acetylcholine, gamma-aminobutyric acid, noradrenaline, serotonin and histamine in the cerebellar cortex of the mouse will be visualized by light-microscopic autoradiography of receptor-bound ligands. The localization of the receptors to regions and/or layers of the cerebellar cortex during postnatal development will be studied with special emphasis on the developmental stage at which receptors first appear. We will attempt to correlate the appearance of receptors with other known ontogenetic events, such as cell migration and synapse formation. MIce with genetic mutations affecting the structure, organization and development of the crebellar cortex will be used in studies aimed at elucidating the cellular localization of neurotransmitter receptors and/or any abnormalities in their normal pattern of development. to determine to what extent receptor appearance and localization is governed by the orderly structure and connections of the cerebellar cortex, cells from the rat cerebellum will be grown in dispersed cell culture and receptors visualized by autoradiography of receptor-bound ligands at various developmental stages. The stage of cerebellar development in culture at which receptors become """"""""functional"""""""" will be studied by the autoradiographic localization of changes in 2-deoxy-D-glucose utilization following administration of receptor agonists. Monoclonal antibodies, directed against cell surfaces of rat cerebellar neurons will be raised in mice to obtain reagents necessary for the identification of neuronal cell types in culture. These neurochemical studies could lead to a better understanding of malfunctions affecting the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS018089-07
Application #
3398148
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1981-12-01
Project End
1989-11-30
Budget Start
1988-09-01
Budget End
1989-11-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Garrett, K M; Haque, D; Berry, D et al. (1997) The GABAA receptor alpha 6 subunit gene (Gabra6) is tightly linked to the alpha 1-gamma 2 subunit cluster on mouse chromosome 11. Brain Res Mol Brain Res 45:133-7
Alam, K Y; Frostholm, A; Hackshaw, K V et al. (1996) Characterization of the 1B promoter of fibroblast growth factor 1 and its expression in the adult and developing mouse brain. J Biol Chem 271:30263-71
Evans, J E; Frostholm, A; Rotter, A (1996) Embryonic and postnatal expression of four gamma-aminobutyric acid transporter mRNAs in the mouse brain and leptomeninges. J Comp Neurol 376:431-46
Wu, C H; Frostholm, A; De Blas, A L et al. (1995) Differential expression of GABAA/benzodiazepine receptor subunit mRNAs and ligand binding sites in mouse cerebellar neurons following in vivo ethanol administration: an autoradiographic analysis. J Neurochem 65:1229-39
Zdilar, D; Luntz-Leybman, V; Frostholm, A et al. (1992) Differential expression of GABAA/benzodiazepine receptor beta 1, beta 2, and beta 3 subunit mRNAs in the developing mouse cerebellum. J Comp Neurol 326:580-94
Frostholm, A; Zdilar, D; Chang, A et al. (1991) Stability of GABAA/benzodiazepine receptor alpha 1 subunit mRNA expression in reeler mouse cerebellar Purkinje cells during postnatal development. Brain Res Dev Brain Res 64:121-8
Zdilar, D; Rotter, A; Frostholm, A (1991) Expression of GABAA/benzodiazepine receptor alpha 1-subunit mRNA and [3H]flunitrazepam binding sites during postnatal development of the mouse cerebellum. Brain Res Dev Brain Res 61:63-71
Russo-Neustadt, A; Rotter, A; Frostholm, A (1991) Distribution of muscarinic receptors in the developing rodent cerebellum. Brain Res 548:179-86
Neustadt, A; Frostholm, A; Rotter, A (1988) Topographical distribution of muscarinic cholinergic receptors in the cerebellar cortex of the mouse, rat, guinea pig, and rabbit: a species comparison. J Comp Neurol 272:317-30
Neustadt, A; Frostholm, A; Rotter, A (1988) On the cellular localization of cerebellar muscarinic receptors: an autoradiographic analysis of weaver, reeler, Purkinje cell degeneration and staggerer mice. Brain Res Bull 20:163-72

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