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

左右肢体的协调运动是四足动物和两足动物运动活动的主要特征之一。这些动物在运动过程中有节奏的肢体运动的基本运动模式是由位于脊髓内的神经元网络产生的。本研究旨在揭示左右协调回路的神经机制及其在发育过程中的功能分化。在新生大鼠离体脊髓标本中，灌流5-HT等神经活性物质可诱发协调的节律性运动活动。这种节律性活动在左右运动神经元中表现为交替模式，在阻断甘氨酸能抑制性突触传递后，这种模式转变为同步模式。然而，在胎儿早期协调节律活动开始时，在出生前左右两侧变为交替模式之前，可以观察到左右两侧之间的同步模式。阻断GABA_A受体介导的兴奋性突触传递可使同步模式中断。在切断新生儿和胎儿脊髓的腹侧连合后，两侧之间的这些协调活动消失，表明左/右交替所需的CIN仅限于脊髓的腹侧区域，并将其轴突投射到腹侧连合。逆行追踪定位了脊髓腹内侧区的一组独特的CIN。此外，我们发现，这些CINs表现出与运动神经元活动相对应的节律性活动，这表明这些神经元在产前发育期间参与运动回路和脊髓CPG。

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.