(from Abstract) The long term objective of the current proposal is the attainment of a greater understanding of the functional organization of the basal ganglia. Substantial evidence suggests that many neurological and psychiatric disorders, including Parkinson's disease, Huntington's disease, Sydenham's chorea, torsion dystonia, Tourette's syndrome and schizophrenia, may result from abnormalities in the activity of these nuclei. Progress in understanding the etiology of these disorders, and in developing treatments for them, is largely dependent on advances in understanding the basic nature of basal ganglia functioning. The proposed experiments are designed to examine basal ganglia by using the immunocytochemical detection of immediate early genes (IEGs) as markers for neurons affected by various behavioral or pharmacological manipulations. The striatum is the largest nucleus within the basal ganglia and is the primary terminus of input into this system. The first set of studies will examine the pharmacological and behavioral control of IEG expression within this structure with emphasis on the patterning of IEG expression with respect to the striosome/matrix compartmentation of the striatum. The striatum contains a number of neuroactive compounds including dopamine, serotonin, adenosine, acetylcholine and substance P and the role played by these substances in controlling striatal IEG expression will be examined. The applicants will also examine the role of dopamine in IEG expression induced by shuttling behavior and characterize the cells that express IEGs under these conditions. Events occurring within the striatum can only influence behavior by affecting the activity of neurons within other parts of the brain. The second group of studies will therefore use IEG expression as a tool to investigate the basic organization of extrastriatal circuitry related to the basal ganglia. Experiments will examine the ability drugs microinjected directly into the striatum, or other basal ganglia nuclei, to influence IEG expression at extrastriatal sites. Other studies will examine the effects of lesions within the basal ganglia on the IEG expression induced by systemic administration of dopaminergic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS033992-04A1
Application #
2807476
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (02))
Program Officer
Murphy, Diane
Project Start
1998-12-01
Project End
2003-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Wirtshafter, David (2007) Rotation and immediate-early gene expression in rats treated with the atypical D1 dopamine agonist SKF 83822. Pharmacol Biochem Behav 86:505-10
Wirtshafter, David (2006) The selective m1 muscarinic antagonist MT-7 blocks pilocarpine-induced striatal Fos expression. Brain Res 1085:127-31
Wirtshafter, David; Osborn, Catherine V (2005) The atypical dopamine D1 receptor agonist SKF 83959 induces striatal Fos expression in rats. Eur J Pharmacol 528:88-94
Wirtshafter, David (2005) Cholinergic involvement in the cortical and hippocampal Fos expression induced in the rat by placement in a novel environment. Brain Res 1051:57-65
Stratford, Thomas R (2005) Activation of feeding-related neural circuitry after unilateral injections of muscimol into the nucleus accumbens shell. Brain Res 1048:241-50
Stratford, Thomas R; Wirtshafter, David (2004) NPY mediates the feeding elicited by muscimol injections into the nucleus accumbens shell. Neuroreport 15:2673-6
Wirtshafter, David (2004) Role of dopamine D1 receptors in the striatal and cortical fos expression induced by the muscarinic agonist pilocarpine. Eur J Pharmacol 488:85-90
Wirtshafter, David; Osborn, Catherine V (2004) The distribution of m4 muscarinic acetylcholine receptors in the islands of Calleja and striatum of rats and cynomolgus monkeys. J Chem Neuroanat 28:107-16
Gao, Leyi; Barber-Singh, Jennifer; Kottegoda, Sumith et al. (2004) Determination of nitrate and nitrite in rat brain perfusates by capillary electrophoresis. Electrophoresis 25:1264-9
Wirtshafter, David; Asin, Karen E (2003) Effects of haloperidol and clozapine on Fos expression in the primate striatum. Neuroreport 14:2429-32

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