THE THALAMOSTRIATAL SYSTEM IN PRIMATES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本项目的目的是阐明组织的martamatergic投射到纹状体的MPTP治疗帕金森病猴的形态学变化。去年完成了两个主要的系列实验。 首先，我们使用皮质纹状体和丘脑纹状体系统（分别为vGluT 1和vGluT 2）的特定标记物来评估MPTP治疗的帕金森病猴纹状体中突触连接模式和相对丰度的变化。获得的数据得出以下结论：（1）帕金森病猴纹状体中皮质终末密度显著增加，表明皮质纹状体系统功能的变化代表了灵长类帕金森病病理生理学的一个关键特征，（2）相反，MPTP治疗猴中丘脑纹状体终末的相对密度不受影响，但它们的突触组织模式发生了重大变化。 为了进一步了解纹状体神经元的形态学变化，与帕金森病条件下纹状体的多巴胺能纹状体传入的重组有关，我们分析了MPTP治疗的猴子纹状体投射神经元上棘密度的变化，发现多巴胺耗尽后纹状体棘减少了50%。我们还表明，棘的丢失与纹状体多巴胺变性的水平密切相关，并且“直接和间接”的离纹状体通路的棘在多巴胺耗尽后都会丢失。 总之，这些发现提供了强有力的证据，在正常和帕金森病条件下的灵长类纹状体的两个主要神经元传入的可塑性和差异组织的高水平。

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. The aim of this project was to elucidate morphological changes in the organization of glutamatergic projections to the striatum of MPTP-treated parkinsonian monkeys. Two main series of experiments were completed during the past year. First, we used specific markers of the corticostriatal and thalamostriatal systems (vGluT1 and vGluT2, respectively) to assess changes in their pattern of synaptic connectivity and relative abundance in the striatum of MPTP-treated parkinsonian monkeys. Data obtained led to the following conclusions: (1) There is a significant increase in the density of cortical terminals in the striatum of parkinsonian monkeys, suggesting that changes in function of the corticostriatal system represent a key feature of Parkinson's disease pathophysiology in primates, (2) In contrast, the relative density of thalamostriatal boutons is not affected in MPTP-treated monkeys, but there was a significant change in their pattern of synaptic organization. To further understand morphological changes in striatal neurons that relate to the reorganization of the glutamatergic striatal afferents to the striatum in parkinsonian conditions, we analyzed changes in the density of spines on striatal projection neurons in MPTP-treated monkeys, and found a reduction of as much as 50% striatal spines after dopamine depletion. We also showed that the loss of spines was tightly linked to the level of striatal dopamine degeneration and that spines of both the "direct and indirect" striatofugal pathways are lost following dopamine depletion. Together, these findings provided strong evidence for the high level of plasticity and differential organization of the two main glutamatergic afferents to the primate striatum in normal and parkinsonian conditions.