The Role of Parafascicular Thalamic Circuits in Action Generation

项目摘要 束旁核是所谓的板内核群中的主要核团。虽然 传统上被认为是网状激活系统的一部分， 唤醒和注意，它对行为的贡献仍然知之甚少。大部分工作 在现代交叉策略发展之前， 选择性细胞类型靶向和神经回路解剖。本建议旨在阐明 Pf电路的特定组件的计算功能，并确定这是如何 电路可用于控制注意力和动作选择。初步结果表明 Pf在快速作用的产生中起关键作用，这似乎是由直接介导的。 来自上级丘的深层/中层的兴奋性输入。两个群体 的Pf投射神经元靶向不同的下游结构，并具有不同的行为 功能协调发展的我们推测，Pf的投射到丘脑底核，特别是 重要的是快速行动启动，绕过典型的基底神经节电路， 众所周知的Pf向纹状体的投射并不需要动作启动，这表明， Pf-基底神经节通路具有独特功能。高度综合的方法将是 采用，结合1）用于3D中的连续行为量化的运动捕捉; 2） 来自单个神经元的无线体内记录; 3）限定的神经元的光遗传学操纵 群体; 4）遗传定义的个体神经元的1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 处理来自中脑的输入，并使用这些信息来指导行动选择， 向纹状体和纹状体的不同输出投射。

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.