Dynamic Basal Ganglia Saccade Networks

描述(由申请人提供)：临床数据强烈表明，包括纹状体在内的基底节与眼球跳动的控制有关。例如，帕金森氏病和亨廷顿病都会出现眼跳缺陷。实验证据还表明，纹状体和基底节环路在眼球运动控制中起着关键作用。纹状体有显著的眼跳相关活动，该区域接受新皮质动眼相关区域的投射，包括额叶眼野、辅助眼野和尾侧背外侧前额叶皮质。纹状体本身的动眼带投射到黑质网状部，黑质再投射到上丘，抑制上丘，从而抑制眼跳。这个基底节通路被用作基底节释放功能的一个主要例子。我们提出了一个实验方案来研究Maccaca Mulatta在学习和随后的一系列任务(包括视觉引导的顺序扫视任务)过程中动眼运动、纹状体和动眼运动皮质区域的反应特性。我们已经开发了一种慢性多电极记录方法，用于猕猴执行一系列眼跳任务。我们将在3个目标中检验3个假设。在目标1中，我们假设纹状体动眼运动区和相应皮质区域的神经元的许多反应特性是由经验建立的。我们将在获取一组定义的任务期间进行记录，以验证这一假设。在目标2中，我们假设当猕猴执行到达任务时，序列选择活动将发生在基底节。为了验证这一假设，我们将训练猕猴在触摸屏上完成眼睛注视下的任务。在目标3中，我们假设自发产生的眼跳序列将在大脑中通过序列选择活动来表示。我们将通过在猕猴进行扫视和伸臂任务时植入纹状体和皮质的多个电极的记录来检验这些假设。我们的目标是最大限度地利用收集的数据，以了解这些在健康和疾病中具有高度临床重要性的通路对眼球运动的控制作用。基底节对于正常的运动是至关重要的，包括顺序运动。重复运动障碍是基底节功能障碍的标志。我们的目标是阐明在这些致残的人类条件下无序的机制。

DESCRIPTION (provided by applicant): Clinical data strongly implicate the basal ganglia, including the striatum, in the control of saccadic eye movements. For example, saccade deficits occur both in Parkinson's disease and in Huntington's disease. Experimental evidence also points to the critical role of the striatum and basal ganglia circuits in oculomotor control. The striatum has prominent saccade-related activity, and this region receives projections from oculomotor-related areas of the neocortex including the frontal eye fields, the supplementary eye fields and the caudal dorsolateral prefrontal cortex. The oculomotor zone of the striatum itself projects to the substantia nigra pars reticulata which in turn projects to, and inhibits the superior colliculus and inhibits saccades thereby. This basal ganglia pathway is used as a prime example of the release functions of the basal ganglia. We propose an experimental program to study in Maccaca mulatta the response properties of the oculomotor striatum and oculomotor cortical areas during learning and subsequent performance of a series of tasks including visually-guided sequential saccade tasks. We have developed chronic, multi-electrode recording methods for use as macaques perform a battery of saccade tasks. We will test 3 hypotheses in 3 Aims. In Aim 1, we hypothesize that many of the response properties of neurons in the oculomotor zone of the striatum and corresponding cortical regions are built up by experience. We will record during acquisition of a defined set of tasks to test this hypothesis. In Aim 2, we hypothesize that sequence-selective activity will occur in the basal ganglia as macaques perform reaching tasks. To test this hypothesis, we will train macaques on a touch screen reaching task under ocular fixation. In Aim 3, we hypothesize that spontaneously produced sequences of saccades will be represented in the brain by sequence-selective activity. We will test these hypotheses by recording from multiple electrodes implanted in the striatum and cortex as macaques perform saccade and arm reaching tasks. We aim to maximize the usefulness of the data collected for understanding oculomotor control exerted by these highly clinically important pathways in health and disease. The basal ganglia are critical for normal movements including sequential movements. Repetitive movement disorders are a hallmark of basal ganglia dysfunction. Our goal is to illuminate mechanisms disordered in these disabling human conditions.