THALAMOSTRIATAL SYSTEMS AND PARKINSON?S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的目标是阐明帕金森氏病动物模型中丘脑向纹状体投射的突触组织和可塑性。在报告期间，我们使用了免疫细胞化学、电子显微镜和共聚焦显微镜，以及大鼠和猴子的顺行轴突追踪方法。此外，我们还发现MPTP处理的猴子的壳核中皮质纹状体、vGluT1免疫反应阳性、谷氨酸能终末的密度显著增加。相反，含有vGluT2的丘脑-纹状体传入神经元的密度没有明显变化，但含有vGluT2的轴突与轴-树突触的比率沿尾核和壳核的吻尾轴方向发生了复杂的变化。 这些发现表明，纹状体的丘脑和皮质传入对多巴胺耗竭的反应在突触可塑性程度上存在显着差异。了解到纹状体谷氨酸能传递异常是帕金森病的一个关键病理特征，我们的发现为更深入地理解帕金森病这种神经化学异常的来源和机制提供了进一步的证据。

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. This project's goal is to elucidate the synaptic organization and plasticity of thalamic projections to the striatum in animal models of Parkinson's disease. During the reporting period, we used immunocytochemistry, electron and confocal microscopy, and anterograde axonal tract tracing methods in rats and monkeys. Additionally, we demonstrated a significant increase in the density of corticostriatal, vGluT1-immunoreactive, glutamatergic terminals in the putamen of MPTP-treated monkeys. In contrast, no significant change was found in the density of vGluT2-containing, thalamostriatal afferents, but complex changes in the ratio of axospinous to axodendritic synapses formed by vGluT2-containing was found along the rostrocaudal axis of the caudate nucleus and putamen. These findings demonstrate striking differences in the degree of synaptic plasticity of thalamic and cortical afferents to the striatum in response to dopamine depletion. Knowing that abnormal striatal glutamatergic transmission is a key pathological feature of Parkinsonism, our findings provide further evidence towards a deeper understanding of the sources and mechanisms that underlie this neurochemical anomaly in Parkinson's disease.