Basis of changes in left-right coordination of rhythmic motor activity during development in the rat spinal cord.

The basic neuronal networks generating coordinated rhythmic motor activity, such as left-right alternate limb movement during locomotion in mammals, are located in the spinal cord. In rat fetuses, the spatial pattern of the rhythmic activity between the left and right sides is synchronous at and shortly after rhythmogenesis before the pattern becomes alternate by birth. The neuronal mechanisms underlying these developmental changes in the left-right coordination were examined in isolated spinal cord preparations. Calcium imaging of commissural neurons at the early fetal stages revealed that the intracellular Ca2+ concentration of the commissural neurons was elevated by bath-application of 5-hydroxytryptamine (5-HT) in synchrony with the simultaneously recorded rhythmic activity of the ventral root, suggesting that the commissural neurons mediate the left-right coordination of the rhythmic activity from onset of the rhythmogenesis. Using a longitudinal split-bath setup, we show that the synchronicity in pattern of the rhythmic activity is the result of excitatory connections being formed via commissural neurons between the rhythm-generating networks located in the left and right spinal cord. During this period, such connections were found to be mediated by excitatory synaptic transmission via GABA(A) receptors. When the pattern of rhythmic activity became left-right alternate at later fetal stages, these connections, still via GABA(A) receptors, were mediating reciprocal inhibition between the two sides. Nearer birth, glycine receptors took over this role. Our results reveal the nature of the neuronal mechanisms forming the basis of the left-right coordination of rhythmic motor activity during prenatal development.