The output of the inferior olive, described as climbing fibers in the cerebellar cortex, has been implicated as playing a critical role in """"""""cerebellar learning"""""""". Changes in olivary output result in significant alterations in the firing pattern of Purkinje cells in the cerebellar cortex. The nature of olivary output is modified by multiple afferent systems and by local inhibitory circuits which have been postulated to play a role in regulating the synchronous firing of olivary neurons. Further, it has been shown that serotonin (5HT) may be the neurochemical mediator of local inhibitory circuits. However, in addition to 5HT at east two other putative inhibitory neurotransmitters have been identified-enkephalin (ENK) and gamma aminobutyric acid (GABA).
The specific aims of this proposal are: 1) to compare the distribution of 5HT, ENK and GABA in the inferior oolivary complex of the rat using the indirect peroxidase antiperoxidase (PAP) technique of Sternberger (13); 2) to identify the cell bodies of origin for these putative neurotransmitters to the inferior olivary complex using a double labeling technique which combines retrograde transport of horseradish peroxidase with the PAP technique in order to identify the putative neurotransmitters used by reticulo-olivary neurons; and 3) to determine the physiological and morphological characteristics of serotoninergic neurons in the medullary reticular formation, especially those which participate in the local circuitry of the inferior olivary complex, using a double labelling technique which combines intracellular recording and staining of individual neurons with fluorescent immunohistochemical techniques (30-34). These neurons will be analyzed at the light and electron microscopic level in order to determine the nature of their interaction in the olivary coplex. In summary, the manner in which information is processed within a nucleus has a direct relationship on its output. In the olivo-cerebellar circuit, suble changes in climbing fiber input may result in significant alterations in Purkinje cell responsiveness and ultimately in cerebellar output. Thus, data obtained in this project should extend our knowledge of the role local circuits in the inferior olivary complex play in cerebellar mediated movements.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS018028-04
Application #
3398056
Study Section
Neurology A Study Section (NEUA)
Project Start
1982-02-01
Project End
1988-02-29
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
4
Fiscal Year
1985
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; 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; 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; King, J S (1985) An immunohistochemical study of serotonin development in the opossum cerebellum. Anat Embryol (Berl) 171:325-38

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