THE THALAMOSTRIATAL SYSTEM IN PRIMATES

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。 列出的子项目的总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 有令人信服的证据，从动物模型和帕金森病（PD）患者的尸检人脑纹状体棘丢失是一个关键的神经病理学特征的PD。已知纹状体的神经元传入的目标树突棘，这些数据似乎很难调和的生理研究表明过度活跃的皮质纹状体神经元系统在啮齿类动物模型的帕金森病，和证据的表达增加的囊泡谷氨酸转运蛋白I型（vGluT 1），一个标记的皮质终端，在纹状体的PD患者和MPTP治疗的猴子。根据其他脑区的数据表明轴棘突触的形态和功能之间的紧密相关性，我们进行了详细的超微结构分析皮质纹状体（vGluT 1阳性）和丘脑纹状体（vGluT 2阳性）轴棘突触正常和MPTP治疗的猴子使用3D电子显微镜的方法。从这一分析中可以得出三个主要结论：（1）与含有皮质vGluT 1的终末接触的棘具有更大的体积，并且比与vGluT 2免疫反应性丘脑终末接触的棘具有显著更大的突触后密度（PSD），（2）丘脑的一个子集，但不是皮质的，在正常和MPTP处理的猴中，终末显示多突触连接模式;（3）皮质和丘脑轴棘突触发生超微结构变化（更大的棘体积，更大的PSD，更大的突触前末端），表明帕金森病动物中突触活动增加。

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. There is compelling evidence from animal models and postmortem human brains of Parkinson's disease (PD) patients that striatal spine loss is a key neuropathological feature of PD. Knowing that striatal glutamatergic afferents target dendritic spines, these data appear difficult to reconcile with physiological studies showing overactivity of the corticostriatal glutamatergic system in rodent models of parkinsonism, and evidence for an increased expression of the vesicular glutamate transporter type I (vGluT1), a marker of cortical terminals, in the striatum of PD patients and MPTP-treated monkeys. In light of data from other brain regions suggesting a tight correlation between morphology and function of axo-spinous glutamatergic synapses, we undertook a detailed ultrastructural analysis of corticostriatal (vGluT1-positive) and thalamostriatal (vGluT2-positive) axo-spinous glutamatergic synapses using a 3D electron microscopic approach in normal and MPTP-treated monkeys. Three main conclusions can be drawn from this analysis: (1) The spines contacted by cortical vGluT1-containing terminals have a larger volume and harbor significantly larger post-synaptic densities (PSDs) than those contacted by vGluT2-immunoreactive thalamic boutons, (2) A subset of thalamic, but not cortical, terminals display a pattern of multisynaptic connectivity in normal and MPTP-treated monkeys and (3) Both cortical and thalamic axo-spinous synapses undergo ultrastructural changes (larger spine volume, larger PSDs, larger pre-synaptic terminal) indicative of increased synaptic activity in parkinsonian animals.