UC San Diego

Locomotion is a ubiquitous behavior demonstrated by the majority, if not all animals. However, the methods by which various animals propel their bodies through water or air, or traverse the land are widely divergent. A common element of locomotion is the motor neuron, the final step of the nervous system that connects to and activates the necessary muscles to achieve locomotion. Motor neuron activity is coordinated both by descending input from the brain and by local interneuron circuitry. The neuronal circuits that govern locomotion are known as central pattern generators, and the roles of the various classes of interneurons during locomotion are known. Motor neurons are the output cell of these neuronal circuits, but additional roles for motor neurons in the development and function of locomotor circuitry have not been explored in great detail. Based on the genetic programs governing motor neuron differentiation and their central role in transmitting interneuron control into muscle activation and limb movement, we hypothesized an active role for motor neurons in specifying and training locomotor circuitry during development. To test this hypothesis, we studied locomotion patterns in mouse mutants with changes in motor neuron transcription factor or axon guidance molecule expression. In addition, we developed computational analysis methods to quantify subtle differences in motor output from wild-type and mutant spinal cords. The results delineate a novel role for motor neurons in the development and function of the circuitry governing locomotion and suggest novel principles regarding circuit formation and neuronal diversity in the central nervous system