The striatum has distinct mu opioid receptor rich clusters of cells called striosomes, which are embedded in an extrastriosomal matrix. Our long term goal is to determine the role of striosomes in health and disease. The specific hypothesis is that striosomes and their output pathways are functional units that select and organize complex movement sequences and their pathology contributes to symptoms of Huntington's disease. The hypothesis is based on reports (1) that striosomes are selectively vulnerable in Huntington's disease patients (Hedreen & Folstein, 1995), (2) striosomes show increase Fos immunoreactivity during repetetive movements (Canales & Graybiel, 2000) and (3) striosome volume postively correlates with a complex movement in a Huntington's disease mouse model (Lawhorn et al, 2005).
The specific aims are to: 1 Test the hypothesis that striosomes are selectively damaged in a Huntington's disease mouse model, 2. Determine whether striosomes are necessary to perform a complex sequencing task and an accelerating rotarod task by lesioning the mu opiod receptor clusters of cells in the striatum, and 3. Determine a functional correlate of striosomes using 2-deoxyglucose autoradiography in normal behaving animals. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS055592-01
Application #
7112849
Study Section
Special Emphasis Panel (ZRG1-F01-R (20))
Program Officer
Sutherland, Margaret L
Project Start
2006-04-20
Project End
2008-04-19
Budget Start
2006-04-20
Budget End
2007-04-19
Support Year
1
Fiscal Year
2006
Total Cost
$55,707
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Lawhorn, C; Smith, D M; Brown, L L (2009) Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task. Neuroscience 163:109-19
Lawhorn, Collene; Smith, Diane M; Brown, Lucy L (2008) Striosome-matrix pathology and motor deficits in the YAC128 mouse model of Huntington's disease. Neurobiol Dis 32:471-8