OPTO-LOCO · Unraveling the circuits of locomotion with opto-genetic manipulation of neuronal activity in awake behaving animals

Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements. The manipulation of electrical activity and cell signaling in specific neuron type using light gated receptors enables us today to dissect the specific neuronal circuits forming the CPGs, and understand the dynamic role of sensory inputs in awake behaving animals.During my work in UC Berkeley, I developed the use of light gated receptors in vivo (Szobota 2007, Pautot 2008 and Wyart 2009). This novel approach enables us to test directly the role of specific pattern of activity in genetically identified neurons for shaping the complex locomotor behaviors.Using a combination of targeted gene expression and optical tools for monitoring and manipulating neuronal activity (“optogenetics”) in awake behaving animals, we have revealed the role of mysterious cells present at the interface between the spinal cord and the central canal: the cerebrospinal fluid (CSF) contacting neurons. I demonstrated that during early development in low vertebrates these cells provide the positive drive to the spinal central pattern generators for spontaneous locomotion (Wyart et al 2009).My future plan focuses on investigating further the circuits of locomotion in the healthy and severed spinal cord. My project consists in three distinct aims:Aim 1. To examine the chemo- and mechano-sensory functions of spinalCSF-contacting neuronsAim 2. To elucidate the role of dynamic sensory feedback for triggeringtransitions during locomotionAim 3. To improve recovery of function after spinal cord injury usingoptogenetics