Mechanisms of Motor Control in the Spinal Cord

National Institute Of Neurological Disorders And Stroke

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Abstract

We seek to understand how the cells and circuits of the spinal cord encode neural programs for motor behavior. During this fiscal year, we made two major advances in our work. First, we tracked the developmental emergence of mouse spinal cord dorsal horn neurons, studying how dozens of different cell types diversify and become spatially organized. We found that a combination of temporal progression and a previously undescribed spatial gradient in progenitors diversify dorsal horn neurons, generating dozens and dozens of distinct types from a single shared progenitor pool. We also tested the hypothesis that excitatory dILB neurons represent the crucial neural element for establishing the laminar microcircuit structure of the spinal dorsal horn. Indeed, we found that removing these cells significantly perturbed laminar organization of remaining neural elements, while removing inhibitory dILA neurons or afferent sensory neurons did not impact structure. Second, we uncovered a modular organization of jumping behavior in mice by revealing distinct movement phases (preparation, propulsion, flight, and landing) that can each be modulated differently depending on jumping purpose (voluntary or reflexive), jump distance, and the ability to interrupt the behavior with a conflicting movement. A modular organization has been theorized to enable flexible and robust motor control across a wide variety of animal behavior, but the neural elements that coordinate modules is not known. We next took advantage of the quantitative behavior analysis we had developed to study jumping and tested the hypothesis that spinal neurons may be responsible. We identified a specific population of neurons, derived from the dILB6 lineage, that can elicit the full "flight" phase of jumping, including tail and hindlimb flexion. While this work is not yet complete, it marks a major step forward in revealing how networks of neurons mediate behavior.