Functional Development of Motor Networks

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 DESCRIPTION (provided by applicant): Movements underlie all forms of vertebrate behavior and are driven by excitatory and inhibitory circuitry within the spinal cord. During locomotion, these networks generate rhythmic commands to motor neurons innervating muscles in the limbs and trunk. In all vertebrates, the motor neurons and their target musculature (motor units) are organized as functional synergists and antagonists. While excitatory circuits ensure the coordinated activation of functionally synergistic motor units, inhibitory circuits maintain the alternation of functionally antagonistic ones. As movements are generated with greater intensity, larger motor units that can exert greater force are recruited into the active pool in an orderly fashion that matches features related to their size, excitability and target musculature. However, regardless of intensity of locomotion, antagonistic motor units are typically activated in alternation. Despite decades of work studying the spinal inhibitory circuitry responsible for left-right or flexor-extensor alternation, relatively little is known about how inhibition is organized o ensure the appropriate activation of motor units of differing sizes during variations in movement speed or strength. Our goal is to determine the existence of systematic patterns of reciprocal inhibition that help coordinate the recruitment patterns of spinal motor neurons during locomotion using zebrafish as a model system. We will test the hypothesis that the strength of inhibitory synaptic connections arises in an orderly fashion during development and is mapped according to speed within motor neurons, such that inhibition at faster speeds arrives early and more proximally, while inhibition at slower speeds arrives later and more distally. The patterns we reveal here will provide critical mechanistic insight into the normal functional integration of inhibition and motor neuron excitability, disruptions of which underlie numerous motor diseases and disorders.