The Role of Parafascicular Thalamic Circuits in Action Generation

束旁丘脑回路在动作生成中的作用

• 批准号: 10609886
• 负责人: Henry Yin
• 金额: $ 40.11万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10609886
• 关键词: 3-Dimensional; Architecture; Area; Arousal; Attention; Basal Ganglia; Behavior; Behavior monitoring; Behavioral; Behavioral Assay; Bypass; Calcium; Cell Nucleus; Cells; Clinical; Corpus striatum structure; Development; Disease; Dissection; Dopamine; Electrophysiology (science); Ganglia; Generations; Image; Impairment; Individual; Intralaminar Nuclear Group; Learning; Lesion; Mediating; Mental disorders; Midbrain structure; Modernization; Motion; Movement; Neurons; Operant Conditioning; Output; Parafascicular Nucleus; Pathway interactions; Photons; Play; Population; Population Projection; Positioning Attribute; Primates; Process; Resolution; Role; Sensory Neglects; Structure; Structure of subthalamic nucleus; Symptoms; System; Thalamic structure; Work; attentional control; cell type; environmental change; experimental study; flexibility; in vivo; nervous system disorder; neural; neural circuit; novel; optogenetics; superior colliculus Corpora quadrigemina; tool; treatment strategy; wireless

Project Summary The parafascicular nucleus is a major nucleus in the so-called intralaminar group. Although it is traditionally considered part of the reticular activating system and thought to play a role in arousal and attention, its contributions to behavior are still poorly understood. Much of the work on the Pf was done in primates before the development of modern intersectional strategies for selective cell type targeting and neural circuit dissection. This proposal aims to elucidate the computational functions of specific components of the Pf circuit, and to determine how this circuit can be used for the control of attention and action selection. Preliminary results indicate that the Pf plays a key role in rapid action generation, which appears to be mediated by direct excitatory inputs from the deep/intermediate layers of the superior colliculus. Two populations of Pf projection neurons target different downstream structures and have distinct behavioral functions. We hypothesize that Pf projections to the subthalamic nucleus are especially important for fast action initiation that bypasses the canonical basal ganglia circuitry, where as the well-known Pf projections to the striatum is not needed for action initiation, suggesting that the Pf-basal ganglia pathway has a distinct function. A highly integrative approach will be employed, combining 1) Motion capture for continuous behavioral quantification in 3D; 2) wireless in vivo recording from single neurons; 3) optogenetic manipulation of defined neuronal populations; 4) 1-photon calcium imaging of genetically defined individual neurons; and 5) quantitative operant behavioral assays. These tools will be used to determine how the Pf processes inputs from the midbrain and uses this information to guide action selection via distinct output projections to the STN and striatum.

项目概要 束旁核是所谓的板内组中的主要核。虽然它是 传统上认为是网状激活系统的一部分，并被认为在 唤醒和注意力，其对行为的贡献仍然知之甚少。大部分工作 在现代交叉策略发展之前，对 Pf 的研究是在灵长类动物中进行的。 选择性细胞类型靶向和神经回路解剖。该提案旨在阐明 Pf 电路的特定组件的计算功能，并确定如何 电路可用于注意力控制和动作选择。初步结果表明 Pf 在快速行动产生中起着关键作用，这似乎是由直接介导的 来自上丘深层/中层的兴奋性输入。两个种群 Pf 投射神经元针对不同的下游结构并具有不同的行为 功能。我们假设 Pf 投射到丘脑底核尤其重要 对于绕过典型基底神经节电路的快速行动启动很重要，其中 众所周知的 Pf 对纹状体的预测对于启动行动来说并不是必需的，这表明 Pf-基底神经节通路具有独特的功能。高度综合的方法将是 采用，结合 1) 运动捕捉以进行 3D 连续行为量化； 2） 来自单个神经元的无线体内记录； 3）确定神经元的光遗传学操作 人口； 4) 基因定义的单个神经元的 1 光子钙成像；和 5) 定量操作行为分析。这些工具将用于确定 Pf 如何 处理来自中脑的输入，并使用这些信息来指导行动选择 STN 和纹状体的不同输出投影。