Touching on locomotion: Olise Oputa Diversity Supplement_Nov 15

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Project Summary/Abstract Touch receptors in skin encoding sensory modalities like vibration, indentation, and slip, are critical for adapting the way we walk in response to changes in our environment. However, the spinal cord integration of touch pathways to 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 essential for sensorimotor function. Our overall hypothesis is that this network represents a critical node for integrating touch and proprioceptive 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 an understanding of how touch pathways converge 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 influence specific muscle responses to sensory 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 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. Mr. Oputa’s research will further the efforts outlined in Aim 3 by combining electromyography (EMG) recordings with depth imaging of freely moving mice by testing the specific hypothesis that distinct premotor networks control unique and ethologically relevant movement features. Mr. Oputa’s career development plan was revised with input from Dr. Marguerite Matthews, who provided critical insights into strengthening his neuroscience training and development as a future physician-scientist. In sum, by understanding the final path for movement organization (i.e., the spinal cord), his research will lead to new therapies to improve the quality of life of people suffering from spinal cord research. Thus, this research lays the critical foundation for novel ways of thinking about modulating spinal circuits for improving motor function.