Investigating Cerebellotectal projections in target acquisition

研究目标获取中的小脑顶盖预测

• 批准号: 10451542
• 负责人: Taylor L Yamauchi
• 金额: $ 3.55万
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451542
• 关键词: Address; Area; Behavior; Behavior Control; Behavioral; Brain region; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Contralateral; Critical Pathways; Electrophysiology (science); Environment; Forelimb; Head; Impairment; Investigation; Learning; Lesion; Location; Maps; Measures; Mediating; Methods; Motor; Motor output; Movement; Mus; Nature; Nervous System; Neurons; Neurosciences; Opsin; Output; Persons; Play; Process; Regional Anatomy; Role; Signal Transduction; Specificity; Structure; System; Testing; Time; cell type; cerebellar lesion; cognitive function; comparison control; control trial; excitatory neuron; experimental study; heuristics; insight; kinematics; limb movement; motor control; neural; neural circuit; neural network; novel; optogenetics; prevent; 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.

项目概要 神经系统如何获取目标（即移动到目标并精确停止在目标处的能力） 令人难以置信的精确度是运动控制和系统神经科学的一个基本问题。一个网络 这些过程涉及多个大脑区域，但活动如何跨结构和协调 细胞类型未知。特别是，相互连接的上丘（SC）和小脑 (Cb) 是该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沿其头尾轴的活动位置表示， 头极反映目标捕获；相比之下，Cb 通过提供 基于学习关联的前馈控制信号。虽然之前的调查显示 Cb 和 SC 在引导行为方面具有互补的作用，它们在控制方面相互作用的本质 目标获取的动向尚不清楚。小脑顶盖投射、小脑传入投射 喙侧 SC 中的细胞核 (CbN) 到兴奋性神经元的位置非常理想，可以控制精确的目标捕获。 然而，之前对小脑顶盖投射和 SC 目标神经元的操作受到限制，使用 可逆性损伤持续时间比单次运动长得多，并且缺乏细胞类型特异性， 任何关于小脑输出到上丘的功能是否可以提高目标精度的因果测试 获得。为了解决这些限制，该提案利用了小鼠的闭环行为系统 光遗传学操纵是由精确定向肢体运动的实时运动学触发的 目标获取。将该系统与 CbN 神经元和细胞类型特异性视蛋白的光遗传学控制相结合 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 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捕获中的作用。