Function of Magnocellular Red Nucleus in Reach-to-grasp

描述（由申请人提供）：本提案的长期目标是了解伸手抓握的神经机制。协调的伸手抓握运动对灵长类动物的运动行为至关重要，并且高度依赖于小脑对下行运动命令的贡献，这些命令最终将产生适当的肌肉激活模式。理解小脑参与伸手抓握运动，以及理解传递到脊髓的控制信号的性质，对于理解一般运动的神经控制至关重要。所提出的研究结果与神经修复术、脊髓损伤、中风和运动康复直接相关。 目前的建议的重点关注的灵长类动物大细胞红核（RNm）在感觉运动整合的功能作用。中间小脑及其输出到RNm有助于手和手指的使用方面在达到。大多数前肢RNm神经元在肢体的简单运动过程中不被激活，但在伸手和抓握的协调动作过程中，相同的神经元被强烈激活。这项建议有两个主要目标。一个目标是正式测试RNm神经元的方向选择性，并帮助解决神经元放电是否在抽象，空间（外在）或基于肌肉（内在）的参考系中编码到达方向的问题。第二个目标是区分不同的内在变量，这些变量可能编码在单个RNm神经元的抓握相关放电中，即前肢关节的运动学或肢体肌肉活动的动力学。同时测量单个单位放电与运动学数据和活动的肢体肌肉在任务执行过程中将提供相关性分析，将确定一个单独的神经元的贡献控制运动学或肌肉相关参数的相对强度的基础。行为范例将通过以下方式分离参数：用三种不同的前肢姿势在不同方向上引发伸手抓握运动（目标1），或通过在不同距离处伸手抓握不同直径的销钉（目标2），或通过以不同速度伸手抓握（目标2）。此外，将通过行为测试、记录肢体肌肉活动和测量失活前和失活后任务执行期间的肢体运动学来分析RNm神经元暂时可逆失活导致的行为缺陷（目的3），以确定缺陷是否与记录研究得出的结论相匹配。

DESCRIPTION (provided by applicant): The long-term objective of this proposal is to understand the neural mechanisms underlying reaching to grasp. Coordinated reach-to-grasp movements are of fundamental importance to primate motor behavior and are highly dependent upon cerebellar contributions to the descending motor commands that will ultimately produce the appropriate patterns of muscle activation. Understanding cerebellar participation in reach-to-grasp movements, and understanding the nature of the control signals transmitted to the spinal cord is essential to understanding neural control of movement in general. Results of the proposed studies are directly relevant to neuro-prosthetics, spinal cord injury, stroke, and motor rehabilitation. The focus of the current proposal concerns the functional role of the primate magnocellular red nucleus (RNm) in sensorimotor integration. Intermediate cerebellum and its output to RNm contribute to aspects of hand and finger use during reaching. Most forelimb RNm neurons are not activated during simple movements of the limb but the same neurons are strongly activated during the coordinated action of reaching and grasping. This proposal has two major objectives. One objective is to formally test directional selectivity of RNm neurons and to help resolve the issue whether neuronal discharge encodes reach direction in abstract, spatial (extrinsic) or in muscle-based (intrinsic) frames of reference. The second objective is to distinguish between different intrinsic variables that might be encoded in the reach-to-grasp-related discharge of individual RNm neurons, namely kinematics of forelimb joints or dynamics of limb muscle activity. Measuring single-unit discharge simultaneously with kinematic data and activity of limb muscles during task performance will provide a basis for correlational analyses that will determine the relative strength of an individual neuron's contribution to controlling kinematic or muscle-related parameters. The behavioral paradigms will dissociate parameters by eliciting reach-to-grasp movements in different directions with three different forelimb postures (aim 1), or by reaching to grasp different diameter dowels at varying distances (aim 2), or by reaching to grasp at different speeds (aim 2). In addition, behavioral deficits resulting from temporary, reversible inactivation of RNm neurons (aim 3) will be analyzed by behavioral testing, by recording limb muscle activity, and by measuring limb kinematics during task performance pre- and post-inactivation in order to determine if the deficits match the conclusions reached from the recording studies.