PROPERTIES OF THE MAMMALIAN SPINAL LOCOMOTOR NETWORK

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DESCRIPTION:(adapted from applicant's abstract) The identity of the spinal interneurons that comprise the mammalian central pattern generator (CPG) for locomotion remains largely unknown. It is known that brainstem drive centers can activate the CPG, and the P.I. proposes that descending monoaminergic pathways remodel the spinal CPG for locomotion and may play a role in facilitating interactions within the CPG to allow it to generate rhythmic output. Four major aims are proposed, with increasing levels of analysis: 1) Identify neurons active during the locomotor program using the activity-dependent dye sulforhodamine, and analyze the modulatory actions of monoamines and their agonists on ligand- and voltage-gated conductances in these neurons. 2) Determine the effects of monoamines on the firing properties of locomotor-related interneurons, specifically looking for conditional bursting properties. 3) Identify the 5HT receptor subtypes responsible for activating the locomotor CPG, with specific emphasis on the hypothesis that 5HT-7 receptors are critical to locomotor rhythmogenesis. 4) Determine whether interneurons active during locomotion express 5HT-7 receptors, which could then serve as markers for CPG neurons. These studies will contribute to our understanding of the CPG for locomotion and could aid in recovery after spinal cord injury. Specifically, pharmacotherapeutic strategies to facilitate CPG activation may assist limited reconnections from the brain in activating locomotion. In addition, identification and characterization of the neurons in the CPG may be helpful in future studies involving transplantation of the neurons in the future.