Towards elucidation of circuit mechanisms for feeding-related manual dexterity

阐明与喂养相关的手动灵巧性的电路机制

• 批准号: 9982480
• 负责人: Gordon M Shepherd
• 金额: $ 43.45万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982480
• 关键词: Activities of Daily Living; Animal Model; Area; Behavior; Behavioral; Biological Assay; Cognitive; Complex; Computer software; Data; Data Set; Deglutition; Dependence; Development; Digit structure; Disease; Eating; Electrophysiology (science); Elements; Exhibits; Fingers; Food; Food Analysis; Food Handling; Forelimb; Future; Genetic; Goals; Hand; Head; Health; Impairment; Investigation; Kinesiology; Label; Lead; Manuals; Mastication; Mediating; Methods; Mission; Modeling; Motion; Motor; Motor Cortex; Movement; Mus; Neurobiology; Neurons; Oral cavity; Organism; Outcome; Pathology; Pathway interactions; Play; Process; Public Health; Research; Resolution; Role; Seeds; Sensorimotor functions; Sensory; Speed; Stereotyping; Structure; Thumb structure; Time; United States National Institutes of Health; Viral; Work; base; cell type; deep neural network; dexterity; disability; feeding; flexibility; free behavior; grasp; improved; insight; kinematics; machine learning algorithm; motor behavior; motor control; motor impairment; nervous system disorder; neural circuit; novel; optogenetics; programs; relating to nervous system; sample fixation; spatiotemporal; tool

PROJECT SUMMARY Dexterous food-handling is a critical but still poorly understood type of basic motor behavior. We propose an exploratory research program to investigate how the mouse uses its digits and forepaws to dexterously handle food. Preliminary results suggest that mouse food-handling movements, despite appearing extremely complex, can be decomposed into several types of simpler elements, tentatively identified as distinct and very rapid submovements that exhibit partly stereotyped and partly variable kinematic features. They also suggest that the mouse’s thumb (first digit, or D1; pollex) plays a surprisingly large and previously unrecognized role in dexterous food-handling. To explore these hypotheses and observations, we will first develop an approach for quantitatively characterizing seed-handling behaviors of freely moving mice. For this we will use high-speed, close-up video capture, combined with deep neural network methods for automated markerless tracking (DeepLabCut). We will then develop a novel trial-based paradigm for characterizing seed-handling under the more experimentally controlled conditions of head-fixation. We will combine this approach with tools for optogenetic silencing of either selectively targeted cortical areas or selectively labeled corticospinal neurons in motor cortex, as well as multi- probe/multi-channel linear array recordings of spiking activity in key nodes along sensorimotor pathways. Collectively this work will advance our understanding of the elemental movements involved in the dexterous manipulation of food, providing new insights into this process in a genetically tractable model organism, and opening the way for future studies to dissect the cellular mechanisms in sensorimotor circuits mediating specific aspects of forelimb and digit motor control.

项目概要 灵巧的食物处理是一种至关重要但仍知之甚少的基本运动行为类型。 探索性研究计划，旨在调查老鼠如何利用其手指和前爪灵巧地处理东西 初步结果表明，小鼠的食物处理动作尽管看起来极其复杂， 可以分解为几种类型的更简单的元素，暂时确定为不同且非常快速的 他们还表明，子运动表现出部分固定和部分可变的运动学特征。 小鼠的拇指（第一个数字，或 D1；pollex）在灵巧性方面发挥着令人惊讶的巨大作用，并且以前未被认识到 为了探索这些假设和观察结果，我们将首先开发一种定量方法。 为此，我们将使用高速特写视频来表征自由移动的小鼠的种子处理行为。 捕获，结合深度神经网络方法进行自动无标记跟踪（DeepLabCut）。 然后开发一种新的基于试验的范式，用于在更多的实验条件下表征种子处理 我们将把这种方法与光遗传学沉默工具结合起来。 选择性地靶向皮质区域或选择性地标记运动皮层中的皮质脊髓神经元，以及多 探针/多通道线性阵列记录感觉运动通路关键节点的尖峰活动。 总的来说，这项工作将增进我们对灵巧动作所涉及的基本运动的理解。 操纵食物，为遗传易处理的模型生物体中的这一过程提供新的见解，以及 为未来研究剖析介导特定感觉运动回路的细胞机制开辟了道路 前肢和数字运动控制方面。