Elucidating the role of midline spiking glia and glial crosstalk in rhythmic spinal motor network. – Rhythmoglia

Locomotion relies on repeated sequences of motoneuron activation and subsequent muscle contractions triggered by a rhythmic central pattern generator (CPG) located in the ventromedial part of the lumbar spinal cord. Despite its crucial role, the exact identity of the cells participating to the spinal CPG remain debated. Resolving this question would lift one of the major roadblocks impeding the development of therapeutic strategies to restore rhythmic motor functions in patients with spinal pathologies. Until now, extensive efforts have focused on interneurons located in the ventromedial spinal cord. By contrast, studies investigating the contribution of ventromedial glial cells, more particularly midline radial glia, remain sparse. By investigating how rhythmic activity emerges at fetal stages, we recently discovered that the first motor behavior observed in mice is associated with rhythmic action potentials (AP) generated by midline radial glia. Rhythmic APs propagate from midline radial glia to depolarize ventromedial astrocyte progenitors via gap-junction coupling. Preliminary data suggest that this electrical crosstalk between glial cells could constitute a glial pacemaker that participates to the rhythmic activation of spinal neurons from fetal to adult stages. By combining genetic and optogenetic manipulation of glial cells with electrophysiological and calcium recordings of spinal glia and neurons and analysis of motor function in mice at fetal and postnatal stages, our project will elucidate how the ventromedial glial pacemaker participate to the development and function of motor networks and how its perturbation can lead to motor defects and pathologies.