SPINAL CORD REPAIR · Spinal locomotor circuits: organization and repair after injury

Neural circuits in the spinal cord, called central pattern generators (CPGs), can produce locomotor movements. The locomotor activity pattern is the result of the circuit design and the interplay between the firing properties of the CPG constituent neurons and their synaptic interactions. Spinal cord injury impairs the function of the locomotor circuitry and results in paralysis. An understanding of the molecular mechanisms of the assembly of the spinal locomotor circuitry, the function of its key excitatory components and the intrinsic plasticity in the healthy and injured spinal cord is a prerequisite for designing novel therapeutic methods to restore locomotor function after spinal cord lesion. The work-packages have been designed to elucidate the key molecular pathways responsible for the development and assembly of the spinal circuitry for locomotion. The intrinsic function and modulation the spinal circuitry will be examined in the healthy spinal cord by combining sophisticated molecular, anatomical, pharmacological and electrophysiological tools. The mechanisms of plasticity and reorganization of the circuitry will be examined in the injured spinal cord as will the mechanism to promote regeneration of the lesioned axons. This project will integrate knowledge on the development and normal spinal cord function together with biological interventions aiming at protecting and repairing the injured spinal cord. The gained understanding will offer molecular and cellular foundations that will be instrumental in developing strategies for restoring motor function following spinal cord injury.