Dissecting the visuomotor circuit for saccadic suppression in the superior colliculus

项目摘要 包括老鼠在内的许多物种都使用称为扫视的弹道式重新定向运动来积极探索它们的大脑。 突出刺激的环境。扫视导致视觉感知的瞬时修改，使得其 变得很难看到在扫视时间附近出现的视觉刺激。这种现象被称为 扫视抑制，并且它与整个视觉系统的神经活动减少有关。会聚 一系列证据表明，这种扫视抑制的神经相关性来自视觉和 前运动机制几项研究表明，模拟自生运动相关的 眼扫视足以降低视网膜的视觉灵敏度， 与实际扫视相关。补充研究假设眼跳运动计划是 向视觉系统广播，在视觉系统中，其用于抑制扫视周围时期期间的视觉活动。这 研究表明，在以下条件下， 最小化或排除视觉机制的影响。在这个建议中，我们试图了解视觉是如何 并且扫视抑制的前运动成分由神经电路实现。呢我们一起来 中脑上级丘（SC）是一种视觉脑结构， 被怀疑是一种必然的放电的来源，这种放电抑制了扫视时的视觉活动。 我们想补充这个想法，视网膜的视觉输出本身是由眼跳调制的。我们 假设SC中运动前活动的必然放电和扫视周围调制 的视网膜信号的合作，产生抑制视觉活动的表层的SC 在扫视的时候。在该提案的目标1中，我们将使用以下方法剖析SC中的前运动电路： 光遗传学，化学遗传学，和高密度的单单位活动的体内记录，而小鼠， 扫视在本提案的目标2中，我们将检查SC投射视网膜神经节细胞的扫视周围 使用双光子钙成像和自然视觉刺激的调制。公共卫生意义。这 一项提案旨在了解如何通过解剖视觉和运动前区来实现扫视抑制 这项研究将促进我们对稳定和 扫视时的连续视觉感知，这对于正常视觉行为的进行至关重要。在 此外，这项研究可能会导致在诊断和治疗损伤和疾病， 影响视力系统。

PROJECT SUMMARY Many species, including mice, use ballistic reorienting movements called saccades to actively explore their environment for salient stimuli. Saccades result in a transient modification of visual perception such that it becomes difficult to see visual stimuli which appear around the time of saccades. This phenomenon is called saccadic suppression and it is associated with a decrease in neural activity across the visual system. Converging lines of evidence show that this neural correlate of saccadic suppression arises from a combination of visual and premotor mechanisms. Several studies have shown that the simulating the self-generated motion associated with saccades is sufficient to reduce visual sensitivity in the retina and reproduces the perceptual deficits associated with actual saccades. Complementary studies have hypothesized that the saccade motor plan is broadcast to the visual system where it is used to suppress visual activity during the peri-saccadic epoch. This is supported by studies which demonstrate the persistence of saccadic suppression under conditions which minimize or preclude the effect of visual mechanisms. In this proposal, we seek to understand how the visual and premotor components of saccadic suppression are implemented by neural circuits. We will focus our investigation on the midbrain superior colliculus (SC), a visuomotor brain structure which has long been suspected as the source of a corollary discharge that suppresses visual activity around the time of saccades. We would like to add to this idea that the visual output of the retina is itself modulated by saccades. We hypothesize that a corollary discharge of premotor activity in the SC and the peri-saccadic modulation of retinal signals cooperate to produce suppression of visual activity in the superficial layers of the SC around the time of saccades. In Aim 1 of the proposal, we will dissect the premotor circuitry in the SC using optogenetics, chemogenetics, and high-density in vivo recordings of single-unit activity while mice make saccades. In Aim 2 of this proposal, we will examine SC-projecting retinal ganglion cells for peri-saccadic modulation using two-photon calcium imaging and naturalistic visual stimulation. Public health significance. This proposal aims to understand how saccadic suppression is implemented by dissecting the visual and premotor circuitry in the midbrain SC. This research will advance our understanding of the neural basis for stable and continuous visual perception across saccades which is critical for the conduct of normal visual behavior. In addition, this research could lead to improvements in the diagnosis and treatment of injury and diseases which affect the oculomotor system.