Touching on locomotion: an anatomical and functional analysis of spinal cord circuits that shape the way we move

触及运动：对塑造我们运动方式的脊髓回路进行解剖学和功能分析

基本信息

批准号：
10266790
负责人：
Victoria Eugenia Guadalupe Abraira
金额：
$ 43.28万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10266790
关键词：
Address Affect Afferent Neurons Anatomy Behavior Behavioral Assay Biological Assay Biomedical Research Complex Computer Vision Systems Coupled Cutaneous Data Disease Electrophysiology (science)Environment Extensor Flexor Foundations Genetic Hindlimb Individual Injury Interneurons Investigation Joints Lateral Length Limb structure Link Locomotion Machine Learning Mechanics Modality Motor Motor Activity Motor Neurons Motor Pathways Motor output Movement Muscle Muscle Contraction Neurons Neurosciences Organ Output Parvalbumins Pathway interactions Pattern Positioning Attribute Property Proprioception Proprioceptor Quality of life Reflex action Research Resolution Sensorimotor functions Sensory Shapes Skin Slice Speed Spinal Spinal Cord Spinal cord posterior horn Structure Synapses Technology Testing Touch sensation Walking Work behavioral study cutaneous sensory neurons electrical property genetic approach improved in vivo insight interdisciplinary approach motor behavior motor function improvement mouse genetics multimodality nervous system disorder neural circuit novel novel strategies novel therapeutics programs receptor response sensory input sensory stimulus somatosensory tool vibration

项目摘要

Project Summary/Abstract A central challenge in neuroscience biomedical research is to define the neural circuits that underlie behavior. Investigations of spinal cord circuits are ideally suited to answer these questions: the direct link between sensory input and motor output affords an exquisite experimental tractability that has been leveraged since Sherrington’s pioneering work on the proprioceptive reflex pathway1. Indeed, great progress has been made since then in understanding how proprioceptors (i.e., muscle sensory neurons) shape motor activity. Touch receptors in skin (i.e., cutaneous sensory neurons) encoding sensory modalities like vibration, indentation, and slip, are also critical for adapting the way we walk in response to changes in our environment. However, spinal cord integration of touch pathways that sculpt motor activity remains profoundly poorly understood. To address key conceptual and technical challenges in this field, we have built an extensive mouse genetic toolbox to visualize, quantify and manipulate touch-specific spinal cord circuits. In addition, we merge these powerful genetic tools with motor assays involving high-speed cameras, computer vision, and machine learning to quantify somatosensory behavior with unprecedented sensitivity. Combining these technologies, we identified a novel touch-specific premotor network important for sensorimotor function. Our overall hypothesis is that this network represents a critical node for integrating touch information to influence specific patterns of muscle groups that facilitate both corrective movements during locomotion and motor ‘switching’ during naturalistic behaviors. We interrogate this novel network to address fundamental questions whose answers will enable a deeper understanding of how touch pathways converge in the spinal cord to shape movement. In Aims 1 and 2 we combine genetic approaches, high-resolution synaptic analysis, slice electrophysiology and in-vivo muscle recordings to test the hypothesis that this network integrates multimodal sensory information to coordinate specific muscles in response to cutaneous input. Aim 3 combines joint and muscle activity recordings to test the hypothesis that this network shapes cutaneous responses to facilitate corrective movements during locomotion. We extend these behavioral studies by implementing computer vision and machine learning to parse out naturalistic behaviors into sub- second movements to test the hypothesis that touch-specific premotor networks sculpt how micro-movements are pieced together into complex motor behaviors . By understanding the final path for movement organization (i.e., the spinal cord) our research will lead to new therapies aimed at improving the quality of life of people suffering from a variety of neurological disorders. Thus, this research lays the critical foundation for novel ways to modulate spinal circuits for improving motor function.

项目概要/摘要神经科学生物医学研究的一个核心挑战是定义行为背后的神经回路。脊髓回路的研究非常适合回答以下问题：感觉和感觉之间的直接联系输入和电机输出提供了自谢林顿以来一直被利用的精致的实验易处理性事实上，自那时以来，本体感觉反射通路方面的开创性工作已经取得了巨大进展。了解本体感受器（即肌肉感觉神经元）如何塑造皮肤中的触觉感受器。（即皮肤感觉神经元）编码振动、压痕和滑动等感觉模式，也是然而，脊髓整合对于适应我们的行走方式以适应环境的变化至关重要。塑造运动活动的触觉通路仍然知之甚少。和该领域的技术挑战，我们建立了一个广泛的小鼠遗传工具箱来可视化、量化和此外，我们将这些强大的遗传工具与运动结合起来。涉及高速摄像机、计算机视觉和机器学习的测定，以量化体感结合这些技术，我们发现了一种新颖的触摸特定行为。我们的总体假设是，该网络代表了一个对感觉运动功能很重要的运动前网络。整合触摸信息以影响肌肉群特定模式的关键节点，从而促进两者我们质疑自然行为期间运动和运动“切换”过程中的纠正动作。新颖的网络来解决基本问题，其答案将使人们更深入地了解如何在目标 1 和 2 中，我们结合了遗传方法，高分辨率突触分析、切片电生理学和体内肌肉记录来检验假设该网络集成了多模式感觉信息来协调特定肌肉以响应目标 3 结合关节和肌肉活动记录来测试该网络的假设。我们扩展了这些行为，以促进运动过程中的纠正运动。通过实施计算机视觉和机器学习来将自然行为解析为子行为的研究第二个动作来测试触摸特异性前运动网络如何塑造微动作的假设被拼凑成复杂的运动行为通过了解运动组织的最终路径（即脊髓）我们的研究将带来旨在改善人们生活质量的新疗法因此，这项研究为新方法奠定了重要基础。调节脊髓回路以改善运动功能。