Investigating Cerebellotectal projections in target acquisition

项目总结 神经系统如何在这样的情况下获得目标(即移动到目标并精确停止的能力) 令人难以置信的精确度是运动控制和系统神经科学的基本问题。一个网络 这些过程牵涉到几个大脑区域，但活动是如何跨结构和 细胞类型未知。特别是，相互联系的上丘(SC)和小脑 (Cb)是这一网络的两个主要枢纽：sc的深层包含一张地形图，其中 对侧空间目标的偏心率由活动沿其尾轴线的位置表示， 与之相比，头极反射目标捕获；相比之下，CB通过提供 基于学习关联的前馈控制信号。虽然之前的调查表明CB 和SC在引导行为方面有互补的作用，它们在控制方面的交互作用的性质 目标获取的行动尚不清楚。小脑顶盖投射、小脑传入投射 位于吻侧SC的核团(Cbns)至兴奋性神经元，是控制精确靶点获取的理想位置。 然而，以前对小脑顶盖投射和SC靶神经元的操纵一直是有限的、使用的 比一次运动持续时间长得多的可逆性损害，并且缺乏细胞类型特异性，防止 小脑输出至上丘功能是否能提高靶点精度的因果检验 收购。为了解决这些限制，这项建议利用了一种闭环系统的小鼠在 其中光遗传操作是由精确定位肢体运动的实时运动学触发的 目标获取。将该系统与CBN神经元的光遗传控制和细胞类型特异性视蛋白相结合 兴奋性SC神经元的表达将允许短期可逆地操纵小脑输出和 在精确定向运动的特定运动学位置的兴奋性SC活动，直接询问 小脑对上丘的贡献在控制精确目标获得中的作用。

PROJECT SUMMARY How the nervous system acquires targets (i.e. the ability to move to and stop precisely at a target) with such incredible precision is a fundamental question of motor control and systems neuroscience. A network of several brain regions is implicated in these processes, but how activity is coordinated across structures and cell types is unknown. In particular, the reciprocally-interconnected superior colliculus (SC) and cerebellum (Cb) are two major hubs of this network: The deep layers of the SC contain a topographic map in which the eccentricity of a contralateral spatial target is represented by the location of activity along its rostrocaudal axis, with the rostral pole reflecting target acquisition; the Cb, by contrast, refines movements by providing feedforward control signals based on learned associations. While previous investigations have shown the Cb and SC share complementary roles in orienting behaviors, the nature of their interaction in controlling movement for target acquisition is unclear. Cerebellotectal projections, afferent projections from cerebellar nuclei (CbNs) to excitatory neurons in the rostral SC, are ideally situated to control precise target acquisition. However, previous manipulations of cerebellotectal projections and SC target neurons have been limited, used reversible lesions that lasted much longer than a single movement, and lacked cell-type specificity, preventing any causal test of whether cerebellar output to the superior colliculus functions to enhance precision in target acquisition. To address these limitations, this proposal utilizes a closed-loop behavioral system for mice in which optogenetic manipulation is triggered by the real-time kinematics of precise orienting limb movements for target acquisition. Combining this system with optogenetic control of CbN neurons and cell-type specific opsin expression in excitatory SC neurons will allow for short-term reversible manipulation of cerebellar output and excitatory SC activity at specific kinematic locations of precise orienting movements, directly interrogating the role of cerebellar contribution to the superior colliculus in controlling precise target acquisition.