Neuronal mechanisms for the coordination of left and right limbs during locomotion and its functional differentiation during development

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Coordinated movements of the left and right limbs are one of the main features of locomotor activity in quadrupeds and bipeds. The basic motor patterns underlying rhythmic limb movements during locomotion in these animals are generated by neuronal networks located within the spinal cord. In this study, we focused on revealing the neuronal mechanism of the circuits involved in left/right coordination and their functional differentiation during development. In the isolated spinal cord preparations taken from the neonatal rats, coordinated rhythmic motor activity could be evoked by superfusing neuroactive substances such as 5-HT. This rhythmic activity showed an alternating pattern in the left-right motoneurons which was converted to a synchronous one after blocking glycinergic inhibitory synaptic transmission. However, at the time of onset of coordinated rhythmic activity in the early fetal period, a synchronized pattern can be observed between the left and right sides before they become an alternate pattern just before birth. The synchronizing pattern could be disrupted by blocking GABA_A receptors which is mediating excitatory synaptic transmission during this period. These coordinated activity between the two sides disappears after cutting the ventral commissure in both neonatal and fetal spinal cord, demonstrating that the CINs that are necessary for left/right alternation are restricted to the ventral region of the spinal cord and project their axons across the ventral commissure. Retrograde tracing has localized a distinct group of CINs in the ventromedial region of the spinal cord. Moreover, we revealed that these CINs show rhythmic activity corresponding to the motoneuronal activity which show clear indication of these neurons involved in locomotor circuits and spinal CPG during the prenatal development.