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。协调的伸手抓握动作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，而下行运动命令最终会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、脊髓损伤、中风和运动康复直接相关。

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.