THE THALAMOSTRIATAL SYSTEM IN PRIMATES

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。 帕金森氏病(PD)患者的动物模型和死后人脑有令人信服的证据表明，纹状体脊椎丢失是PD的关键神经病理特征。知道纹状体谷氨酸能传入以树突棘为靶标，这些数据似乎很难与显示帕金森病啮齿动物模型中皮质纹状体谷氨酸能系统过度活跃的生理学研究相一致，以及有证据表明帕金森病患者和MPTP治疗的猴子纹状体中皮质终末的标志泡状谷氨酸转运体I(VGluT1)的表达增加。鉴于来自其他脑区的数据表明轴棘谷氨酸能突触的形态和功能之间存在密切的相关性，我们利用三维电子显微镜方法对正常和MPTP处理的猴子的皮质纹状体(vGluT1阳性)和丘脑纹状体(vGluT2阳性)轴棘谷氨酸能突触进行了详细的超微结构分析。从这一分析可以得出三个主要结论：(1)皮质vGluT1终末接触的脊椎体积和突触后密度(PSD)明显大于vGluT2免疫反应阳性的丘脑终末；(2)在正常和MPTP治疗的猴子中，丘脑的一部分终末显示出多突触连接的模式；(3)帕金森病动物的皮质和丘脑轴棘突触都经历了超微结构的变化(脊椎体积更大，PSD更大，突触前终末更大)，表明帕金森病动物突触活动增加。

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.