This research examines the dopaminergic modulation of cortically-driven striatal immediate-early gene (lEG) expression. Cortical disinhibition induces Fos expression in the dorsolateral portion of the striatum in rats. Previous research has shown that dopamine (DA) has differential effects on striatal neurons, and thus it may modulate striatal response to cortical input. In addition, although the main target of DA-ergic input to the basal ganglia (BG) is the striatum, other BG nuclei receive DA-ergic afferents. The globus pallidus (GP) is an area of the BG that is directly modulated by DA and it also has efferent projections to the striatum. Thus the GP is an area in which DA-ergic modulation can affect striatal function.
The specific aims are: 1) to examine the pattern of cortically driven striatal lEG response in subpopulations of striatal neurons by using double-labeling ICC techniques to visualize Fos and parvalbumin (PV); 2) to examine changes in this pattern due to dopamine depletion; 3) to examine changes in this pattern due to blockade of DA receptors in the GP, using intrapallidal application of sulpiride; and 4) to examine changes in this pattern due to stimulation of DA receptors in the GP using inirapallidal application of quinpirole. By examining the effects of DA, both in the striatum and in the GP, on cortically driven striatal lEG response information will be gained about how DA modulates basal ganglia functioning. This information may provide a basis for understanding mechanisms involved in motor disorders such as Parkinson's disease, and may provide important insights into possible extra-striatal targets for therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32NS041717-01
Application #
6340262
Study Section
Special Emphasis Panel (ZRG1-MDCN-5 (01))
Program Officer
Murphy, Diane
Project Start
2001-06-01
Project End
Budget Start
2001-06-01
Budget End
2002-05-31
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of California Irvine
Department
Neurology
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Trevitt, Jennifer T; Morrow, Joseph; Marshall, John F (2005) Dopamine manipulation alters immediate-early gene response of striatal parvalbumin interneurons to cortical stimulation. Brain Res 1035:41-50