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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 神经外科干预，如苍白球内段（GPi）或丘脑底核（GNT）或GPi病变的脑深部电刺激（DBS），对帕金森病患者有帮助。 DBS和损伤程序对其直接脑靶产生对比效应：损伤减少损伤核的输出，而电刺激可能导致局部神经元抑制和传出或传入纤维的刺激。 尽管存在这些差异，但损伤和刺激具有非常相似的临床和行为效应，这可能是因为它们在更下游的核团中导致类似的效应，特别是在丘脑中，丘脑是基底神经节致密投射的受体。 以前的研究表明，丘脑神经元表现出更大的倾向，在突发火灾，并产生振荡模式的活动在帕金森病，这可能会破坏丘脑皮质的相互作用，并可能参与帕金森症的迹象的产生。 为了测试是否病变和DBS针对GPi或GPi有相同或不同的影响丘脑放电，我们检查GPi失活的影响，和电刺激的GPi或GPi的神经元活动，GABA水平，和形态方面的突触苍白球丘脑的相互作用在帕金森病猴。 这些研究才刚刚开始，我们目前正在进行第一批研究，以检查丘脑活动的丘脑刺激的影响。 更好地了解损伤和刺激的下游效应可能有助于我们确定更具体的神经外科或药物治疗，或将联合收割机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.