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.

项目摘要 灵巧的食物处理是一种至关重要的，但仍然不了解基本运动行为的类型。我们提出了一个 探索性研究计划，以调查鼠标如何使用其数字和前脚来敏捷处理 食物。初步结果表明，鼠标食物处理运动，欲望看起来极其复杂， 可以分解为几种较简单的元素，十个元素被判定为独特且非常迅速 揭示了部分刻板印象和部分变化运动特征的材料。他们还建议 鼠标的拇指（第一位数字或D1； Pollex）在灵巧中扮演着令人惊讶且以前未认识到的作用 食物处理。为了探索这些假设和观察，我们将首先开发一种定量的方法 表征自由移动小鼠的种子处理行为。为此，我们将使用高速，特写视频 捕获，与无标记跟踪（DeepLabcut）的深神网络方法结合使用。我们将 然后开发一种基于试验的新型范式，用于在更实验的情况下表征种子处理 头部固定条件。我们将将这种方法与用于光学遗传沉默的工具结合在一起 运动皮层中有选择性靶向皮质区域或有选择性标记的皮质脊髓神经元 探针/多通道线性阵列记录沿感觉运动途径关键节点中的峰值活动。 这项工作总的来说，将提高我们对敏捷涉及的基本运动的理解 操纵食物，在一般可探讨的模型有机体中为此过程提供新的见解，并 为将来的研究开辟道路，以剖析介导特异性的感觉运动电路中的细胞机制 前肢和数字电动机控制的各个方面。