This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main goal of this project is to characterize the localization and functions of kainate receptors (KARs) in the basal ganglia. To do so, we combine high-resolution electron microscopic procedures to visualize and analyze the subsynaptic and subcellular localization of KARs with in vitro patch clamp recording techniques in brain slices to study the functional effects KARs activation on basal ganglia neuronal activity. Data collected in this project over the past year provide the first evidence for pre- and post-synaptic localization and function of KARS in the rat globus pallidus. In brief, we have shown that KARS are expressed postsynaptically in dendrites and presynaptically in axons and glutamatergic terminals in the rat globus pallidus. Using electrophysiological techniques, we have complemented these immunocytochemical data with pharmacological and electrophysiological studies showing that KARS activation induces postsynaptic depolarization and regulates glutamatergic transmission in the rat GP. These findings pave the way for the future development of novel pharmacotherapeutic approaches aimed at targeting KARS in basal ganglia diseases.
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