The hindlimb locomotor Central Pattern Generator (CPG), located in the lumbar spinal cord, drives repetitive locomotor movements during walk. In a series of experiments we provided demonstration of a new class of interneurons within the hindlimb locomotor CPG, which have the intrinsic ability to oscillate in a frequency range similar to stepping rhythms (see illustration below).
These pacemakers are dependent on the persistent sodium current (INaP). Blocking INaP abolished the rhythmicity of the locomotor movements. This study paves the way for a new working hypothesis in which INaP-dependent pacemaker neurons play a key role in the locomotor rhythm generation. The ultimate goal will be to identify the sodium channel isoform responsible for INaP. One of the major isoforms of the sodium channels within the CNS is the Nav1.6 channel.
The proposal for the Master’s student will be to investigate if Nav1.6 is the molecular determinant of the INaP related to pacemakers and in turn to the locomotor rhythm. The issue will be investigated in Nav1.6-null mutant mice by:
- characterizing behavioral locomotor deficits
- investigating the ability of the locomotor CPG to generate a rhythm by means of patch clamp recordings.