CAREER: High-level control of low-level circuits in the mammalian motor system

职业：哺乳动物运动系统低级电路的高级控制

• 批准号: 2239412
• 负责人: Michael Economo
• 金额: $ 80万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2239412&HistoricalAwards=false
• 关键词: CAREER; level; control; low; circuits

All behavior – everything that an animal does – is defined by their movements. As a result, the control of flexible, dexterous, goal-directed movements is one of the most important functions of the nervous system. Motor circuits in the vertebrate brain are arranged hierarchically. Low-level circuits in the brainstem and spinal cord – such as the central pattern generators that control breathing and locomotion – can autonomously produce basic motor patterns. High-level motor circuits allow animals to learn and adapt movements, detect and correct errors, predict the cost and benefits of actions, and assemble movements into complex sequences to attain behavioral goals over long time scales. High-level circuits do not generally control movements directly, but, instead, engage and modify the basic motor programs produced by low-level circuits. Low-level circuits in turn integrate an array of inputs from many high-level areas to synthesize the motor commands that drive motor neurons and muscles. Little is currently known about how a multitude of high-level motor centers together control low-level circuits in a coordinated fashion, despite the centrality of this process to all flexible behavior. The overarching goal of this project is to identify how high-level regions of the mouse motor system turn on, turn off, and modify the motor patterns produced by low-level circuits. Critically, tackling this problem will differentiate between two competing models of hierarchical control that may be utilized in the mammalian brain. In the Cooperative model, there exists a ‘division of labor’ between high-level motor centers with different circuits responsible for different computational processes – any or all of which may be invoked simultaneously according to behavioral demands. Alternatively, the Parallel model predicts that many high-level brain regions are equally capable of commanding movements in their entirety, with different regions subsuming control in the behavioral context for which they are specialized. This project leverages a cutting-edge experimental toolkit in mice for manipulating neural activity and tracking the signals communicated between them with cell-type specificity. This project focuses on control of a well-defined central pattern generator responsible for controlling tongue movements in mice to leverage a novel paradigm in which mice perform the same tongue movements in contexts associated with different high-level control processes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

所有的行为--动物所做的一切--都是由它们的动作决定的。因此，控制灵活，灵巧，目标导向的运动是神经系统最重要的功能之一。脊椎动物大脑中的运动回路是分层排列的。脑干和脊髓中的低级回路--比如控制呼吸和运动的中央模式发生器--可以自主地产生基本的运动模式。高级运动回路允许动物学习和适应动作，检测和纠正错误，预测动作的成本和收益，并将动作组合成复杂的序列，以实现长期的行为目标。高级回路通常不直接控制运动，而是参与和修改低级回路产生的基本运动程序。低层次的电路反过来又整合了来自许多高层次区域的一系列输入，以合成驱动运动神经元和肌肉的运动命令。目前，我们对多个高级运动中枢如何以协调的方式共同控制低级回路知之甚少，尽管这一过程对所有灵活行为都至关重要。 这个项目的首要目标是确定小鼠运动系统的高级区域如何打开，关闭和修改由低级电路产生的运动模式。至关重要的是，解决这个问题将区分两个竞争模型的分层控制，可能会在哺乳动物的大脑中使用。在合作模型中，高级运动中心之间存在“分工”，不同的回路负责不同的计算过程--其中任何或全部可以根据行为需求同时调用。另一方面，平行模型预测，许多高水平的大脑区域同样能够指挥整个运动，不同的区域将控制纳入其专门化的行为背景中。 该项目利用小鼠的尖端实验工具包来操纵神经活动并跟踪它们之间传递的具有细胞类型特异性的信号。该项目的重点是控制一个明确的中央模式发生器负责控制舌头运动的小鼠，以利用一种新的范式，其中小鼠执行相同的舌头运动的背景下，与不同的高层次的控制过程。该奖项反映了NSF的法定使命，并已被认为是值得支持的评估使用基金会的智力价值和更广泛的影响审查标准。