KAINATE RECEPTORS IN STRIATUM: IMPLICATION WITH EXCITOTOXICITY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本项目的主要目的是表征盐酸盐受体（KARs）在基底神经节中的定位和功能。为此，我们结合高分辨率电子显微镜技术观察和分析KARs的亚突触和亚细胞定位，并结合体外膜片钳记录技术在脑切片中研究KARs激活对基底神经节神经元活动的功能影响。在过去的一年里，本项目收集的数据为大鼠苍白球中KARS的突触前和突触后定位和功能提供了第一个证据。简而言之，我们已经证明KARS在大鼠苍白球的树突突触后表达，在轴突和谷氨酸末端突触前表达。利用电生理技术，我们用药理学和电生理研究补充了这些免疫细胞化学数据，表明KARS激活诱导突触后去极化并调节大鼠GP中的谷氨酸能传递。这些发现为未来开发针对KARS治疗基底神经节疾病的新型药物治疗方法铺平了道路。

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.