Saccade motor control: The role of cerebellum in spatial updating of saccades

扫视运动控制：小脑在扫视空间更新中的作用

• 批准号: 10318570
• 负责人: ROBIJANTO SOETEDJO
• 金额: $ 44.4万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318570
• 关键词: Appearance; Area; Behavioral; Brain; Brain Stem; Cells; Cerebellar Cortex; Cerebellar Diseases; Cerebellar vermis structure; Cerebellum; Cerebral cortex; Development; Diagnostic; Eye; Eye Movements; Feedback; Goals; Interruption; Life; Lobule; Location; Maintenance; Mediating; Monkeys; Motor; Movement; Movement Disorders; Neurons; Nucleus fastigii; Ocular Motility Disorders; Output; Pathway interactions; Patients; Pattern; Physiology; Play; Process; Rehabilitation therapy; Role; Saccades; Signal Transduction; Structure; Testing; Update; Vision; Visual; experimental study; improved; kinematics; motor control; neuromechanism; oculomotor; optogenetics; relating to nervous system; retinotopic; superior colliculus Corpora quadrigemina; vector

Project Summary/Abstract The accuracy and precision of saccades are important to vision. Our long term goal is to identify the neural mechanisms that underlie saccade motor control. As with other movements, the cerebellum plays a key role in fine tuning saccadic eye movements. Specifically, intact oculomotor vermis (OMV) and caudal fastigial nucleus (cFN) is critical for producing accurate saccades. Much of our understanding of the physiology of neurons in the cFN and Purkinje (P-) cells in the OMV during saccades has relied on saccades made to single targets that appear in the visual periphery. In such a visually guided saccade task, the vectors of the retinotopic target and the saccade motor command are congruent. However, in real life, saccades often must be coordinated with other saccades or other types of eye movement that intervene between the programming and execution of a saccade. Such interruptions dissociate the vector of the saccade to be executed from its retinotopic target vector. The brain must update the vector of the upcoming saccade by combining the retinotopic target vector with information about the intervening movement. Oculomotor areas of cerebral cortex account only partially for the spatial updating of saccades, implying significant contribution from subcortical structures. We hypothesize that the OMV and the cFN to which it projects play critical roles in this process. These structures receive motor command feedback from brainstem saccade premotor neurons. The feedback signal could be used to adjust the motor command of the final saccade during spatial updating via cFN projection to saccade premotor neurons. We will test this hypothesis in a monkey performing a double-step saccade task (DST). In this task, the monkey makes two sequential saccades in the dark to previously flashed visual targets. The task requires the brain to combine the motor command of the first saccade with the retinotopic location of the flashed second target to produce an accurate second saccade. Specifics Aims 1 and 2 examine the activity of neurons in the cFN and OMV P-cells during spatial updating of saccades. We will test the hypothesis that by combining the retinotopic target signal in the SC with the feedback motor command of the first saccade of a DST, the cerebellum computes a corrective signal. This corrective signal is represented in the saccade-related activity of the neurons. Specific Aim 3 perturbs the processing of spatial updating of saccades before the second saccade is launched. We will briefly increase P-cell activity by using optogenetic activation triggered by the first saccade, and examine the effects on the second saccades. Overall Impact: The cerebellum plays an important role in the accuracy, precision, and temporal sequencing of movements. We will study the cerebellum’s contribution to the coordination of a sequence of saccades—well understood movements that provide a platform for understanding motor coordination more generally. The results of our studies will improve our understanding of the neural basis of motor coordination and will guide the development of behavioral strategies to rehabilitate patients with cerebellar diseases.

项目总结/摘要 扫视的准确性和精确性对视觉是重要的。我们的长期目标是找出 这些机制是眼跳运动控制的基础。与其他运动一样，小脑在 微调扫视眼球运动。具体而言，完整的眼蚓部（OMV）和尾侧小脑顶 核（cFN）对于产生准确的扫视至关重要。我们对人类生理学的理解 在扫视过程中，OMV中cFN和Purkinje（P-）细胞中的神经元依赖于单次扫视 出现在视觉边缘的目标。在这种视觉引导的扫视任务中， 视网膜定位目标和扫视运动命令是一致的。然而，在真实的生活中，扫视通常必须 与在编程之间介入的其它扫视或其它类型的眼球运动相协调 和扫视的执行。这样的中断使要执行的扫视的向量与其运动分离。 视网膜定位靶向载体。大脑必须通过结合 视网膜定位目标向量与有关干预运动的信息。大脑皮层视区 仅部分解释了扫视的空间更新，这意味着皮层下的显著贡献 结构.我们假设OMV和它投射的cFN在这个过程中发挥着关键作用。 这些结构从脑干扫视前运动神经元接收运动命令反馈。反馈 信号可用于在通过cFN的空间更新期间调整最终扫视的运动命令 投射到扫视前运动神经元。我们将在一只猴子表演两步舞的过程中检验这一假设 扫视任务（DST）。在这项任务中，猴子在黑暗中连续扫视两次， 视觉目标该任务要求大脑将第一次扫视的运动指令与第二次扫视的运动指令联合收割机结合起来。 闪光的第二目标的视网膜位置以产生准确的第二次眼跳。具体目标1和 2.研究了眼跳空间更新过程中cFN和OMV P细胞神经元的活动。我们将测试 假设通过将SC中的视网膜定位目标信号与 在DST的第一次扫视中，小脑计算校正信号。该校正信号表示为 与扫视相关的神经元活动。具体目标3扰乱了空间更新的处理， 在第二次扫视启动之前进行扫视。我们将通过使用光遗传学方法来简单地增加P细胞活性， 激活触发的第一眼扫视，并检查对第二眼扫视的影响。 总体影响：小脑在准确性，精确性和时间方面发挥着重要作用。 运动的顺序。我们将研究小脑对一系列动作协调的作用， 眼跳--易于理解的动作，为更多地理解运动协调提供了平台 一般来说。我们的研究结果将提高我们对运动协调的神经基础的理解 并将指导小脑疾病患者康复的行为策略的发展。