Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington's Disease
Annual rept. 15 Jul 2003-14 Jul 2004
EMORY UNIV ATLANTA GA
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Huntingtons disease HD is a neurodegenerative condition characterized by a loss of projection neurons-in the striatum. Although various hypotheses have been proposed to explain the mechanisms that underlie the striatal neuronal death, excitotoxicity still deserves major interest. Recent findings indicate that changes in the genotype of the kainate receptor subunit, GluR6, are associated with variation in the age of onset of HD, which implicates the kainate receptors in the pathogenesis of HD and other basal ganglia disorders. The localization and functions of kainate receptors in the basal ganglia remain unknown. We, therefore, propose to use state-of-the-art electron microscope techniques and in vitro whole cell patch clamp recording techniques to test a series of hypotheses that will help to elucidate the localization and understand better the role of kainate receptors in the striatum and the globus pallidus. The results of these studies will provide a strong basis for studying the potential mechanisms by which these receptors participate in normal and abnormal basal ganglia functions. Moreover, they will help the development of novel therapeutic strategies aimed at targeting pre-synaptic kainate receptors in HD and other basal ganglia disorders.
- Anatomy and Physiology