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.

项目摘要 束旁核是所谓的板层内群中的一个主要核。尽管它是 传统上被认为是网状激活系统的一部分，并被认为在 唤醒和注意，它对行为的贡献仍然知之甚少。大部分工作 在现代横断面策略发展之前，在灵长类动物中进行了PF研究 选择性细胞类型靶向和神经回路解剖。这项建议旨在澄清 PF电路的特定组件的计算功能，并确定如何 电路可用于控制注意力和动作选择。初步结果显示 Pf在快速动作产生中起关键作用，这似乎是由直接的 来自上丘深层/中间层的兴奋性输入。两个种群 的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投射到丘脑下核是特别重要的 对于绕过规范的基底节回路的快速动作启动很重要，其中AS 众所周知的向纹状体的PF投射不是启动动作所必需的，这表明 PF-基底节通路具有独特的功能。高度整合的方法将是 使用，结合1)运动捕捉用于3D中的连续行为量化；2) 单个神经元的无线活体记录；3)特定神经元的光遗传操作 群体；4)遗传定义的单个神经元的单光子钙成像；以及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，并使用该信息通过 不同的输出投射到STN和纹状体。