Investigating Cerebellotectal projections in target acquisition

研究目标获取中的小脑顶盖预测

• 批准号: 10313163
• 负责人: Taylor L Yamauchi
• 金额: $ 3.38万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10313163
• 关键词: Address; Anatomy; Area; Behavior; Behavioral; Brain region; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Contralateral; Critical Pathways; Electrophysiology (science); Environment; Forelimb; Head; Impairment; Investigation; Lesion; Location; Maps; Measures; Mediating; Methods; Motor; Motor output; Movement; Mus; Nature; Nervous system structure; Neurons; Neurosciences; Opsin; Output; Persons; Play; Process; Role; Signal Transduction; Specificity; Structure; System; Testing; Time; base; cell type; cerebellar lesion; cognitive function; control trial; excitatory neuron; experimental study; heuristics; insight; kinematics; limb movement; motor control; neural circuit; neural network; novel; optogenetics; prevent; relating to nervous system; response; superior colliculus Corpora quadrigemina

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.

项目摘要 神经系统如何获得目标（即移动到目标并精确停在目标处的能力）， 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。网络 几个大脑区域参与了这些过程，但是活动如何在结构之间协调， 细胞类型未知。特别是，相互连接的上级丘（SC）和小脑 (Cb)是这个网络的两个主要枢纽：SC的深层包含一个地形图， 对侧空间目标的偏心率由沿其嘴尾轴的活动位置沿着表示， 与喙极反射目标采集;相比之下，Cb通过提供 前馈控制信号基于学习的关联。虽然之前的调查显示， 和供应链共享互补的作用，在定向行为，其相互作用的性质，在控制 目标获取的移动尚不清楚。小脑顶盖投射，小脑传入投射 核（CbN）到头侧SC中的兴奋性神经元，理想地位于控制精确的目标获取。 然而，以前对小脑顶盖投射和SC靶神经元的操作是有限的， 可逆性病变持续时间比单次运动长得多，缺乏细胞类型特异性， 任何因果测试是否小脑输出到上级丘功能，以提高精度的目标 采集为了解决这些限制，该提议利用小鼠的闭环行为系统， 所述光遗传学操纵由精确定向肢体运动的实时运动学触发， 目标捕获将该系统与CbN神经元和细胞类型特异性视蛋白的光遗传学控制相结合， 在兴奋性SC神经元中的表达将允许小脑输出的短期可逆操纵， 兴奋性SC活动在特定的运动学位置的精确定向运动，直接询问 小脑对上级丘在控制精确目标获取中的作用。