THE THALAMOSTRIATAL SYSTEM IN PRIMATES

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。 多年来，丘脑纹状体系统的解剖结构一直是史密斯博士和他的同事们感兴趣的话题。在之前的资助期间，他们将其电子显微镜解剖学研究扩展到有助于纹状体神经支配的各种丘脑核团，在帕金森氏病动物模型中检查丘脑-纹状体系统的突触可塑性，并观察丘脑刺激对恒河猴纹状体活动的电生理影响。 这些研究获得的主要结论如下：1)超微结构数据显示，存在基于丘脑起源、纹状体中的突触靶点以及与大脑皮层和纹状体的关系程度的双重丘脑-纹状体系统；起源于中央正中核和束旁核的系统，主要针对纹状体神经元的树突，只向大脑皮层提供少量输入；第二系统，源于其他丘脑核，几乎仅以纹状体神经元的树突为靶点，向特定皮质区域提供重要输入，并将轴突发送到与纹状体功能相关的区域。2)他们证明，在帕金森病的非人类灵长类动物模型中，谷氨酸能皮质纹状体和丘脑纹状体系统的超微结构都经历了复杂的可塑性变化。 这些变化很可能是灵长类动物这两种谷氨酸能系统不同电生理特性的基础，并有助于帕金森病纹状体谷氨酸能传递的改变。总之，这些发现为更深入地了解正常和帕金森病患者丘脑纹状体网络的功能组织提供了坚实的基础。 这一信息对于解释和改进使用高频刺激尾侧板层内核作为运动障碍的新治疗方法是至关重要的，包括抽动症和帕金森病。

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 anatomical organization of the thalamostriatal system has been a topic of major interest for Dr Smith and colleagues for the past many years. During the previous funding period, they have expanded their electron microscopic anatomical studies to various thalamic nuclear groups that contribute to striatal innervation, examined the synaptic plasticity of the thalamostriatal system in animal models of Parkinson's disease and looked at the electrophysiological effects of thalamic stimulation upon striatal activity in rhesus monkeys. The main findings obtained in these studies are summarized as follows: 1) Their ultrastructural data revealed the existence of dual thalamostriatal systems based on thalamic origin, synaptic targets in the striatum and extent of relationships with the cerebral cortex and striatum; a system that originates from the centre median and parafascicular nuclei (CM/Pf), which targets preferentially dendritic shafts of striatal neurons and provide only minor inputs to the cerebral cortex, and a second system, which originates from other thalamic nuclei, targets almost exclusively dendritic spines of striatal neurons, provides significant inputs to specific cortical areas and send axon collaterals to functionally related regions of the striatum. 2) They demonstrated that both the glutamatergic corticostriatal and thalamostriatal systems undergo complex plastic changes in their ultrastructural organization in the nonhuman primate model of Parkinson's disease. These changes most likely underlie differential electrophysiological properties of these two glutamatergic systems in primates, and contribute to alterations of striatal glutamatergic transmission in Parkinson's disease. Together, these findings provide a solid foundation for a deeper understanding of the functional organization of the thalamostriatal networks in normal and parkinsonian conditions. This information is critical for the interpretation and refinement of the use of high frequency stimulation of caudal intralaminar nuclei as new treatment of movement disorders including Tourette's syndrome and Parkinson's disease.