Development of interneurons of the mammalian spinal cord locomotor circuits

LANUZA, G.M.

Mexico DF

Simposio; Stem Cells Network Symposium; 2011

Current evidence indicates that motoneurons and different classes of interneurons in the developing spinal cord are specified by the action of transcription factors expressed in discrete domains of neural progenitor cells along the dorso-ventral axis. Although several of the embryonic populations of neurons have been characterized based on their gene expression profiles in the developing embryo, little is known about the identities that they acquire in the mature nervous system and their contribution to functional local circuitry. With this goal, we performed fate-mapping analysis of three classes of ventral embryonic interneurons: V0 (Dbx1+-derived), V1 (En1+) and V2b (Gata3+) neurons. These three populations are inhibitory neurons, but differing in their axonal projections. While V0 neurons synapse onto contralateral neurons, V1 and V2b project their axons ipsilaterally. In order to assess the contribution of different classes of interneurons to the spinal neuronal networks that control walking behaviors, we used a series of genetic approaches that allows the specific manipulation of individual populations. Commissural spinal V0 interneurons, whose fate is controlled by the activity of the homeobox gene Dbx1, has a critical role in coordinating left-right locomotor activity necessary for the sequential stepping of the limbs during walking. The role of V1 and V2b neurons was assess by the expression of the synaptic blocker tetanus toxin under the control of En1 and Gata3 regulatory elements. We found that when synaptic transmission from V1 and V2b interneurons is abolished, the activation of flexor and extensor muscles occurs in synchrony. These results indicate that the alternating flexor and extensor activity needed for limb-driven locomotion is generated by the composite actions of two classes of inhibitory spinal interneurons, V1 and V2b. In summary, these findings identify three classes of embryonic interneurons that are key components of the spinal locomotor circuits that control stepping movements in mammals.