The intent of this proposal is to determine the distribution, origin and physiological effect(s) of two putative neuromodulators, the indoleamine serotonin and the peptide enkephalin, on Purkinje cells in the cat's cerebellum.
The Specific Aims of this proposal are: 1) To determine the lobular and laminar distribution of serotonin and enkephalin in the cat's cerebellum using the peroxidase anti-peroxidation technique. 2) To localize the cells of origin of serotoninergic and enkephalinergic varicosities present within the cerebellum. This will be accomplished by using a double label technique which combines retrograde transport of horseradish peroxidase (HRP) with the PAP technique. 3) To analyze the physiological effects of serotonin and enkephalin on Purkinje cells. Various putative neuroactive substances (e.g. serotonin, enkephalin, glutamate, GABA) will be iontophoresed from multibarrel extracellular recording electrodes and their on Purkinje cell activity recorded. In some experiments an intracellular electrode will be combined with the drug electrode. The location of each unit will be marked either with Fast Green (extracellular recording) or HRP (intracellular recording). The tissue will be processed with the PAP technique to verify the presence of serotoninergic and enkephalinergic varicosities in areas from which physiological data are obtained. 4) To establish the relationship of serotoninergic and enkephalinergic varicosities to other axonal elements within the cat's cerebellum. The spatial relationship of immunoreactive varicosities to Purkinje cells intracellularly injected with HRP will be analyzed. In addition, the cytological characteristics or terminals containing serotonin and enkephalin as well as their synaptic relationships will be determined. The role of these chemically defined systems has not been incorporated into existing theories of cerebellar function as little is known about their effect(s) on specific populations of cortical neurons. It has been proposed that neuromodulators play a role in regulating neuronal activity and that they function to bias or fine tune neural circuits which, ultimately, influence on-going- movements. Thus, data from the proposed studies, when incorporated into our existing concepts of cerebellar physiology, will further extend our knowledge of how individual circuits in the cerebellar cortex contribute to the control and co-ordination of movement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS018028-07
Application #
3398057
Study Section
Neurology A Study Section (NEUA)
Project Start
1982-02-01
Project End
1992-02-29
Budget Start
1988-03-01
Budget End
1989-02-28
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
Bishop, G A (1998) Brainstem origin of corticotropin-releasing factor afferents to the nucleus interpositus anterior of the cat. J Chem Neuroanat 15:143-53
Nelson, T E; King, J S; Bishop, G A (1997) Distribution of tyrosine hydroxylase-immunoreactive afferents to the cerebellum differs between species. J Comp Neurol 379:443-54
Bishop, G A (1995) Calcitonin gene-related peptide modulates neuronal activity in the mammalian cerebellar cortex. Neuropeptides 28:85-97
Gilerovitch, H G; Bishop, G A; King, J S et al. (1995) The use of electron microscopic immunocytochemistry with silver-enhanced 1.4-nm gold particles to localize GAD in the cerebellar nuclei. J Histochem Cytochem 43:337-43
Kerr, C W; Bishop, G A (1992) The physiological effects of serotonin are mediated by the 5HT1A receptor in the cat's cerebellar cortex. Brain Res 591:253-60
Kerr, C W; Bishop, G A (1991) Topographical organization in the origin of serotoninergic projections to different regions of the cat cerebellar cortex. J Comp Neurol 304:502-15
Bishop, G A (1990) Neuromodulatory effects of corticotropin releasing factor on cerebellar Purkinje cells: an in vivo study in the cat. Neuroscience 39:251-7
Bishop, G A; King, J S (1986) Reticulo-olivary circuits: an intracellular HRP study in the rat. Brain Res 371:133-45
Bishop, G A; Ho, R H (1986) Cell bodies of origin of serotonin-immunoreactive afferents to the inferior olivary complex of the rat. Brain Res 399:369-73
Bishop, G A; Ho, R H; King, J S (1985) An immunohistochemical study of serotonin development in the opossum cerebellum. Anat Embryol (Berl) 171:325-38

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