THALAMIC ACTIVITY IN PARKINSONISM (UDALL CENTER, PROJECT #2)

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。 神经外科干预措施，如苍白球内侧节(GPI)或丘脑底核(STN)的脑深部刺激(DBS)，或GPI损毁，对帕金森病患者都有帮助。DBS和损毁程序对其直接的大脑靶点产生不同的影响：损伤减少受损核团的输出，而电刺激可能导致局部神经元抑制，以及刺激传出或传入纤维。尽管有这些差异，但损伤和刺激具有非常相似的临床和行为影响，可能是因为它们在更下游的核团中产生了类似的影响，特别是在丘脑--从基底节接受密集投射的丘脑。以前的研究表明，丘脑神经元表现出更多的爆发式放电和产生帕金森综合征的振荡活动模式，这可能会扰乱丘脑皮质的相互作用，并可能参与帕金森症状的产生。为了测试针对GPI或STN的损伤和DBS对丘脑放电的影响是否相同或不同，我们观察了GPI失活以及电刺激STN或GPI对帕金森病猴神经元活动、GABA水平和突触相互作用的形态方面的影响。这些研究才刚刚开始，我们目前正在进行第一批研究，以考察刺激STN对丘脑活动的影响。 更好地了解损伤和刺激的下游影响可能有助于我们定义更具体的神经外科或药物治疗，或将药物治疗与神经外科干预相结合的治疗。

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. Neurosurgical interventions, such as deep brain stimulation (DBS) of the internal pallidal segment (GPi) or the subthalamic nucleus (STN), or GPi lesions, are helpful in patients with Parkinson's disease. DBS and lesioning procedures produce contrasting effects on their immediate brain targets: Lesions reduce the output of the lesioned nucleus, while electrical stimulation may lead to local neuron inhibition, and stimulation of efferent or afferent fibers. Despite these differences, lesions and stimulation have remarkably similar clinical and behavioral effects, perhaps because they lead to similar effects in nuclei further downstream, particularly in the thalamus, the recipient of a dense projection from the basal ganglia. Previous studies have suggested that thalamic neurons show an increased tendency to fire in bursts and to generate oscillatory patterns of activity in parkinsonism, which may act to disrupt thalamocortical interactions, and may be involved in the generation of parkinsonian signs. To test whether lesions and DBS aimed at GPi or STN have the same or different effects on thalamic firing we examine the effects of GPi inactivation, and of electrical stimulation of the STN or GPi on neuronal activities, GABA levels, and morphological aspects of the synaptic pallidothalamic interactions in parkinsonian monkeys. These studies have just started, and we are currently doing the first studies to examine the effects of STN stimulation on thalamic activities. A better understanding of the downstream effects of lesions and stimulation may help us to define more specific neurosurgical or pharmacological therapies, or therapies that combine pharmacologic treatments with neurosurgical interventions.