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

项目摘要/摘要 眼跳的准确性和精确度对视力很重要。我们的长期目标是识别神经 作为跳跃运动控制基础的机制。与其他运动一样，小脑在 微调眼球跳动。特别是，完整的动眼蠕虫(OMV)和尾尖 核团(CFN)是产生准确眼跳的关键。我们对人的生理学的大部分理解 OMV中CFN和Purkinje(P-)细胞的神经元在眼跳时依赖于单次眼跳 出现在视觉外围的目标。在这种视觉引导的扫视任务中， 复视靶点和扫视运动指令是一致的。然而，在现实生活中，扫视经常必须 与其他眼跳或其他类型的眼球运动协调在节目之间 和执行一次扫视。这样的中断将要执行的扫视的向量与其 视网膜定位靶向量。大脑必须更新即将到来的扫视的矢量 具有介入运动信息的视网膜定位目标向量。大脑皮层动眼区域 仅部分解释了眼跳的空间更新，这意味着皮质下的显著贡献 结构。我们假设OMV和它所投射到的CFN在这一过程中发挥关键作用。 这些结构接受脑干跳动前运动神经元的运动指令反馈。反馈 在通过CFN进行空间更新的过程中，可以使用信号来调整最终扫视的运动指令 投射到跳动前神经元。我们将在一只猴子身上测试这一假设 扫视任务(DST)。在这项任务中，猴子在黑暗中进行了两次连续的扫视，以避免先前的闪光 视觉目标。这项任务需要大脑将第一次扫视的运动指令与 对闪光的第二个目标进行视网膜定位，以产生准确的第二次扫视。具体目标1和 2检测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中的视网膜定位靶信号与反馈运动指令相结合 在DST的第一次扫视时，小脑计算校正信号。该校正信号被表示为 与眼跳相关的神经元活动。特定目标3扰动空间更新的过程 在第二次扫视开始之前进行扫视。我们将通过使用光遗传技术来短暂地提高P细胞的活性 由第一次扫视触发的激活，并检查对第二次扫视的影响。 总体影响：小脑在准确性、精确度和时间性方面发挥着重要作用 动作的顺序。我们将研究小脑对一系列 眼跳-为更多地了解运动协调提供平台的众所周知的动作 一般说来。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 并将指导制定行为策略，以康复小脑疾病患者。

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.