ANATOMICAL AND PHYSIOLOGICAL CHARACTERIZATION OF THE THALAMOSTRIATAL SYSTEM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 丘脑和纹状体之间的相互作用与基底节功能障碍有关，如帕金森氏病。丘脑中央正中核/束旁核(CM/PF)的脑深部刺激在缓解与这些疾病相关的运动症状方面是有效的；然而，其治疗效果受到对丘脑纹状体系统功能的极少了解的阻碍。本研究旨在研究非人灵长类动物CM/PF-纹状体的解剖和功能关系，以了解丘脑-纹状体系统在基底节功能障碍中的作用。我们的研究结果表明，胆碱能中间神经元主要通过局部注射GABA能药物而使CM活性降低而对CM的激活作出反应。在解剖学研究中，用免疫组织化学方法对中棘神经元(MSN)和纹状体胆碱能中间神经元(SCI)进行免疫组织化学双重标记，以确定在SCI上观察到的GABA能输入的哪一部分来自纹状体的主要细胞群MSN。我们的发现表明，SCI主要接受沿其整个躯体树突域的对称性突触输入，其中MSN侧支约占这些突触输入的四分之一。综上所述，纹状体内GABA能微电路在调节SCI对CM激活的反应中起着重要作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The interaction between the thalamus and the striatum has been implicated in disturbances of basal ganglia function such as Parkinson's disease. Deep brain stimulation of the centromedian/parafascicular (CM/PF) thalamic nuclei is effective in relieving motor symptoms associated with these conditions; however, its therapeutic effects are hampered by the minimal information known about the function of the thalamostriatal system. This study aims to examine the CM/PF-striatal anatomical and functional relationship in nonhuman primates, in order to understand the involvement of the thalamostriatal system in basal ganglia dysfunction. Our findings show that cholinergic interneurons mainly respond to CM activation by decreased activity, which is mediated by the local injection of GABAergic drugs. In the anatomical studies, immunohistochemistry at the electron microscopic level was double-labeled with neuronal markers for medium spiny neurons (MSNs) and striatal cholinergic interneurons (SCIs), in order to determine what portion of the GABAergic inputs observed onto SCIs are derived from MSNs, the main cell group of the striatum. Our findings demonstrate that SCIs mainly receive symmetric synaptic inputs along their entire somatodendritic domain, where MSN collaterals comprise about one quarter of these synaptic inputs. In conclusion, intrastriatal GABAergic microcircuitry is shown to be in a position to play an important role in modulating the responses of SCIs to the activation of the CM in monkeys.