BASAL GANGLIA FUNCTION--BASIC MECHANISMS AND EFFECTS

基底神经节（BG）是一组皮质下核团，在控制随意运动中起着至关重要的作用。 它们的重要性被BG疾病所强调，例如帕金森氏病，这损害了自愿运动的启动和执行。 虽然人们对边防军的一般组织结构了解很多，但关于他们在正常控制行动方面的作用仍然存在根本问题。 考虑到对恢复性神经外科手术（如慢性电刺激）的重新关注，这些问题特别相关。针对BG来缓解帕金森病症状本研究的主要目的是了解BG在正常运动控制中的作用，使用清醒行为的猕猴作为实验系统。 第一个目标解决了一个有趣的悖论BG：虽然影响BG的疾病引起的问题，启动自愿运动，大多数神经生理学研究发现，在BG的神经元活动发生得太晚，在运动启动中发挥作用。然而，在大多数这些研究中，运动是对外部感官刺激的反应。 有证据表明，帕金森病患者的刺激提示运动比自我发起的运动受到的影响要小。 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-自我发起的运动是何时进行的或进行了哪些运动。 第二个目标是解决直接和间接BG途径的作用。 BG的输出受到两种不同的通路的影响，对运动具有相反的影响：来自纹状体的直接通路促进运动，以及通过丘脑底核（subthalamic nucleus，简称BCN）的间接通路抑制运动。 虽然这些途径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存在许多问题。 我们将测试一个假设，这两个途径可能会采取一致行动，以“选择”一个特定的运动之间的竞争的运动的可能性，通过检查如何在输出核的BG神经元的影响，由电失活的神经元。 为此目的，有必要研究电刺激对海马神经元的影响。 尽管电刺激现在被用于治疗人类患者的帕金森病症状，但对神经元的影响知之甚少。 我们将直接测量电刺激对大脑皮层神经元的影响，并研究这些影响如何随刺激参数而变化。 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脑深部部位。 结合基础研究和技术创新将增加我们对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.