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The role of striosomes in basal ganglia function

$55,944F31FY2007NSNIH

Albert Einstein College Of Medicine, Bronx NY

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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. [unreadable] [unreadable] [unreadable]

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