Collaborative Research:Excitatory Interneurons in the Mouse Locomotor Pattern Generator

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This proposal will study the evolution of neural networks that drive locomotion in vertebrates. To understand how animals locomote, it is necessary to identify and study the neurons in the networks that control locomotion. Homologs of a set of excitatory interneurons that participate in locomotor control in fish and tadpoles have now been identified in the mouse spinal cord, based on their expression of the Chx10 transcription factor gene. This proposal will determine whether the function of these Chx10 cells has been conserved in mammals. Optical imaging using calcium-sensitive dyes will be used to study the activity of the Chx10 neurons during the locomotor activity evoked by tail stimulation or transmitter application to the isolated spinal cord. The principal investigator of the collaborative proposal has generated transgenic mice lacking the Chx10 neurons, which will be used to study the effects of this loss on locomotor activity in the isolated spinal cord. Finally, the firing properties of Chx10 neurons will be studied as well as their modulation by serotonin, which helps to initiate locomotion. It is expected that these neurons are essential for normal locomotion, though altered movements (such as synchronous galloping activity) may still occur in the absence of these neurons. Serotonin should modify these neurons to prepare them for participation in the locomotor network. This project will help train a postdoctoral fellow and a minority undergraduate to study the organization and function of neural networks that generate simple rhythmic behaviors.