Electrophysiological Characterization of V2a Interneurons and Their Locomotor-Related Activity in the Neonatal Mouse Spinal Cord

Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord

“…Most cells firing action potentials at resting membrane potential were rhythmic during locomotor-like activity (25 of 38), with firing centered around phase values of 0.25 or 0.75, which corresponds to the peak activity in either the ispilateral or contralateral segmental ventral roots. This timing of rhythmic spike activity in the Chx10 population along the cord is corresponding to what is found for L2 Chx10 neurons described in an accompanying paper (Zhong et al, 2010). Notably, the percentage of rhythmically active spiking Chx10 neurons in the two studies is comparable at low locomotor frequencies (ϳ40%).…”

“…Intracellular fills revealed diverse projection patterns with most Chx10 interneurons having local projections. Our data, together with data from an accompanying paper (Zhong et al, 2010), demonstrate that Chx10 neuron rhythmicity, synaptic input, and morphology are consistent with V2a neurons regulating segmental left-right alternation and ipsilateral motor neuron firing during locomotion and having little effect on rhythm generation.…”

“…Notably, the percentage of rhythmically active spiking Chx10 neurons in the two studies is comparable at low locomotor frequencies (ϳ40%). We were unable to induce locomotor activity with middle to high frequencies possibly because the dorsal horn was removed along the entire lumbar cord [unlike the study by Zhong et al (2010), in which the dorsal horn was removed only over L2]. We could therefore not determine whether a higher percentage of cells would be active at higher locomotor frequencies as observed in the accompanying paper (Zhong et al, 2010).…”

Generation of V2a Interneurons from Mouse Embryonic Stem Cells

“…V2a interneurons have been shown to be involved in repetitive motor behaviors in the CPGs of the spinal cord and medial reticular formations of the hindbrain and play an important role in left-right coordination of locomotion, skilled reaching movements, and rhythmic patterning of breathing [10,14,26]. Differentiation of V2a interneurons from mESCs has the potential to increase understanding developmental pathways and possibly provide a source for cell therapies in high cervical spinal cord injuries affecting respiratory and motor function.…”

“…Cells in the p2 progenitor domain express Irx3, Lhx3, and Foxn4 [19][20][21][23][24][25] and mature into three distinct interneuron classes, V2a, V2b, and V2c. V2a interneurons are excitatory, glutamatergic, and express Chx10 and Lhx3 [17,18,26], whereas V2b interneurons are inhibitory, GABAergic/glycinergic, and express Gata3 [24,[27][28][29][30][31][32]. Newly identified V2c interneurons arise from a subset of V2b interneurons, and their function in CPG networks is still unknown [33,34].…”