Basal Ganglia - Cortical Interactions in Motor Control

基底节是运动系统的重要组成部分。基底节疾病会导致自主运动受损或不正常的非自主运动，或两者兼而有之。人们普遍认为，在控制行为的许多方面，基底神经节与大脑皮层机制是协调一致的。基底节-丘脑皮质回路的很大一部分专门用于控制运动。尽管在了解这些回路对运动控制的贡献方面取得了实质性的进展，但对于基底节的输出如何影响皮质运动区，仍然没有达成共识。这项拟议的实验将研究基底节-丘脑皮质回路在灵长类动物肢体运动控制中的功能。选择性灭活苍白球内侧部基底节输出神经元 (GPI)将与记录猴子执行手腕运动任务时大脑皮质目标的神经元活动相结合。我们假设，基底神经节在自主运动中的一个关键功能是促进所需的运动模式，同时抑制潜在的竞争运动模式，以便它们不会干扰已选择的运动模式。我们将在两个具体目标上检验这一总体假设。我们将确定辅助运动区(SMA)和主运动区的运动相关神经元信号是如何 大脑皮质(MC)在GPI可逆性失活后的变化，以及这些信号变化与由此导致的运动障碍的关系。我们还将确定GPI活动是否与“自动”运动反应的抑制相关，以及GPI的失活是否阻止了该反应的抑制，并干扰了与“自动”反应相反方向的运动的执行。这些实验将直接测试失活肢体运动的基底节输出对大脑皮层运动生理学的影响。他们将提供关于基底神经节如何与大脑皮层运动区相互作用的重要新信息。这一研究结果将加深对运动控制中正常的基底节功能的理解，并将为研究基底节疾病引起的运动障碍的病理生理学提供重要线索。更好地了解这些机制将对开发更好的运动障碍治疗方法产生潜在的重大影响。

The basal ganglia are important components of the motor system. Diseases of the basal ganglia cause impaired voluntary movement, abnormal involuntary movements, or both. It is generally agreed that the basal ganglia function in concert with cerebral cortical mechanisms in the control of many aspects of behavior. A large portion of the basal ganglia-thalmocortical circuitry is devoted to the control of movement. Despite substantial advances in understanding the contributions of these circuits to motor control, there is still no consensus as to how the basal ganglia output influences cortical motor areas. The proposed experiments will investigate the function of basal ganglia-thalamocortical circuits in the control of limb movement in primates. Selective inactivation of basal ganglia output neurons in globus pallidus, pars interna (GPi) will be combined with recording neuronal activity in cortical targets of that output while monkeys perform a wrist movement task. We have hypothesized that a key function of the basal ganglia in voluntary movement is to facilitate the desired motor pattern and to simultaneously inhibit potentially competing motor patterns so that they do not interfere with the one that has been selected. We will test this overall hypothesis in 2 specific aims. We will determine how movement-related neuronal signals in supplementary motor area (SMA) and primary motor cortex (MC) change after reversible inactivation of GPi and how those signal changes relate to the resulting motor impairment. We will also determine if GPi activity correlates with suppression of an "automatic" movement response and whether inactivation of GPi prevents suppression of that response and interferes with performance of a movement in the opposite direction from the "automatic" response. These experiments will directly test the effect on cortical motor physiology of inactivating the basal gangia output for limb movements. They will provide important new information on how the basal ganglia interact with motor areas of cerebral cortex. This results of this project will enhance understanding of normal basal ganglia function in motor control and will provide important clues to the pathophysiology of movement disorders resulting from basal ganglia diseases. Better understanding of these mechanisms will have potential significant impact on development of better therapies for those movement disorders.