Dissecting the roles of glutamatergic receptor subtypes in spinal locomotor circuit function

PROJECT SUMMARY Abstract Animal survival is dependent on locomotion to successfully find shelter, locate a mate, capture prey, and avoid predators. Although it is well established that spinal locomotor circuits in vertebrates are activated by glutamatergic-mediated excitation, our understanding of glutamatergic signaling is incomplete. This is important to understand since glutamatergic excitation contributes to the generation of rhythmic activity and the amplitude of motor output. Dissecting the precise role that subtypes of ionotropic and metabotropic glutamate receptors play in spinal locomotor circuit function will provide mechanistic data critical for understanding locomotor circuit function. We will address this gap in knowledge by determining the roles of glutamate receptor subtypes in the larval zebrafish spinal locomotor network using a well-validated complement of tools that span from molecular to behavioral levels, including optogenetic activation of spinal locomotor networks, pharmacology, electrophysiology, high-speed videography, and calcium imaging. The goal of this proposal is to advance our mechanistic understanding of glutamatergic signaling responsible for regulating the properties of vertebrate spinal locomotor output and spinal motor neuron recruitment. The results of these experiments will set a foundation for investigations into the specific neuronal targets of glutamatergic actions, revealed here, in a future R01 proposal. Since many principles of CPG function are conserved across vertebrates, we expect these findings to translate to other animals, including humans.