Most models of movement disorders arising from basal ganglia disease, including Huntington's disease, tardive dyskinesia and Parkinsonism, are based upon the concept of striatal dopaminergic-cholinergic balance. Diseases that disrupt this balance result in movement disorders; pharmacological manipulations that tend to restore this balance constitute the usual treatments. A series of experiments is proposed that is designed to elucidate the structural and functional role of the cells that subserve one half of this balance: the neostriatal cholinergic local circuit neurons. (1) Using the method of intracellular recording and HRP filling, type I large neurons will be characterized electrophysiologically and then filled with HRP to reveal their morphology (which will be examined at the light microscopic level). (2) Type I large aspiny neurons, filled by HRP, will be examined at the electron microscopic level and compared to choline acetyltransferase(ChAT)-immunoreactive neurons, with the goal of establishing the identity of the two. (3) The relationship of type I large neurons to the enkephalin-rich patch and enkephalin-poor matrix compartments will be examined using a combined intracellular HRP and immunoperoxidase method. The connections from spiny projection neurons to ChAT-immunoreactive neurons will also be examined with the electron microscope, as will local afferents that are immunoreactive for glutamic acid decarboxylase, enkephalin, and substance P.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Unknown (R23)
Project #
7R23NS024897-01
Application #
3450143
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1986-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
East Carolina University
Department
Type
Schools of Medicine
DUNS #
City
Greenville
State
NC
Country
United States
Zip Code
27858