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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：
10656220
负责人：
Victoria Eugenia Guadalupe Abraira
金额：
$ 42.86万
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/10656220
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 Maps Mechanics Modality Motor Motor Activity Motor Neurons Motor Pathways Motor output Movement Muscle Muscle Contraction Neurons Neurosciences Organ Output Parvalbumins Pathway interactions Pattern Persons 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 Vertebral column Visualization 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.

项目总结/文摘