ANATOMICAL AND PHYSIOLOGICAL CHARACTERIZATION OF THE THALAMOSTRIATAL SYSTEM

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子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神经节功能紊乱如帕金森病有关。 丘脑中央核/束旁核（CM/PF）的脑深部刺激可有效缓解与这些疾病相关的运动症状;然而，其治疗效果受到有关丘脑纹状体系统功能的最少信息的阻碍。 本研究的目的是检查CM/PF-纹状体的解剖和功能的关系在非人灵长类动物，以了解丘脑纹状体系统参与基底神经节功能障碍。 我们的研究结果表明，胆碱能中间神经元主要通过降低活性来响应CM激活，这是由局部注射GABA能药物介导的。 在解剖学研究中，免疫组织化学在电子显微镜水平上用中棘神经元（MSN）和纹状体胆碱能中间神经元（SCI）的神经元标记物进行双重标记，以确定在SCI上观察到的GABA能输入的哪一部分来自MSN，纹状体的主要细胞群。 我们的研究结果表明，SCI主要接受对称的突触输入沿着他们的整个体树突域，MSN侧支包括约四分之一的这些突触输入。 总之，纹状体内的GABA能微电路被证明是在一个位置，发挥重要作用，在调节反应的SCI激活的CM在猴子。

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.