BASAL GANGLIA FUNCTION--BASIC MECHANISMS AND EFFECTS

基底节(BG)是一组皮质下核团，在控制自主运动中起着至关重要的作用。帕金森氏症等BG疾病突显了它们的重要性，这些疾病损害了自愿运动的发起和执行。虽然关于BG的一般组织已知很多，但关于它们在正常运动控制中所起的作用，基本问题仍然存在。鉴于人们对慢性电刺激等恢复性神经外科手术重新产生了兴趣，这些问题尤其相关。以BG为目标以缓解帕金森症状的药物。这项研究的主要目的是以清醒的猕猴为实验系统，了解BG在正常运动控制中的作用。第一个目的是解决关于BG的一个有趣的悖论：虽然影响BG的疾病会导致启动自主运动的问题，但大多数神经生理学研究发现，BG中的神经元活动发生得太晚，无法在运动启动中发挥作用。然而，在这些研究中，大多数运动都是对外部感官刺激的反应。有来自帕金森患者的证据表明，刺激提示的运动比自我发起的运动受到的影响较小。因此，我们将研究BG是否在自我发起的运动中发挥特殊作用-无论是在何时进行运动还是在进行哪种运动方面。第二个目标涉及直接和间接BG途径的作用。BG的输出受到两条截然相反的运动通路的影响：一条来自纹状体的直接通路促进运动，另一条通过丘脑底核(STN)的间接通路抑制运动。虽然这些通路的识别为理解运动障碍提供了一个有用的框架，但关于它们在正常运动中的作用仍有许多问题。我们将通过检测BG输出核团中的神经元如何受到STN电失活的影响来检验一个假设，即这两条通路可能协同作用，在相互竞争的运动可能性中“选择”一个特定的运动。为此，有必要研究电刺激对STN的神经元影响。尽管STN刺激现在被用于治疗人类患者的帕金森症状，但对神经元的影响知之甚少。我们将直接测量电刺激对STN中神经元的影响，并研究这些影响如何随着刺激参数的变化而变化。为此，我们将开发和测试新的多电极技术，用于同时记录和电刺激多个深部大脑部位。基础研究和技术创新相结合将增加我们对BG在正常运动和运动障碍中的作用的理解，并有望为治疗帕金森病提供新的方法。

The basal ganglia (BG) are a set of subcortical nuclei that play a crucial role in the control of voluntary movements. Their importance is underscored by diseases of the BG, such as Parkinson's disease, which compromise the initiation and execution of voluntary movements. While much is known about the general organization of the BG, fundamental questions remain about their role in the normal control of movement. These questions are particularly relevant given the renewed interest in restorative neurosurgical procedures, such as chronic electrical stimulation. that target the BG to relieve Parkinsonian symptoms. The main goal of this is to understand the role of the BG in the normal control of movement, using the awake behaving macaque monkey as an experimental system. The first aim addresses an intriguing paradox about the BG: while diseases affecting the BG cause problems with initiating voluntary movements, most neurophysiological studies have found that neuronal activity in the BG occurs too late to play a role in movement initiation. However, in most of these studies the movements were in response to an external sensory stimulus. There is evidence from Parkinsonian patients that stimulus-cued movements are less severely affected than self-initiated movements. We will thus examine whether the BG play a special role in self-initiated movements - self-initiated with respect to either when a movement is made or which movement is made. The second aim addresses the roles of the direct and indirect BG pathways. The output of the BG is influenced by two distinct pathways with opposing effects on movement: a direct pathway from the striatum which facilitates movement, and an indirect pathway via the subthalamic nucleus (STN) which inhibits movement. While the identification of these pathways has provided a useful framework for understanding movement disorders, many questions remain about their roles in normal movement. We will test one hypothesis, that the two pathways may act in concert to "select" a specific movement among competing possibilities of movement, by examining how neurons in the output nuclei of the BG are affected by electrical inactivation of the STN. For this purpose, it will be necessary to examine the neuronal effects of electrical stimulation in the STN. Little is known about the neuronal effects, even though STN stimulation is now being used to treat Parkinsonian symptoms in human patients. We will directly measure the neuronal effects of electrical stimulation in the STN, and examine how these effects vary with the parameters of stimulation. For this we will develop and test new multielectrode techniques for recording from and electrically stimulating multiple deep brain sites simultaneously. The combined basic studies and technical innovations will increase our understanding of the role of the BG in normal movement and movement disorders, and will hopefully provide new approaches for treating Parkinsonian conditions.