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

运动过程中左右肢协调的神经机制及其发育过程中的功能分化

基本信息

批准号：
12480245
负责人：
KUDO Norio
金额：
$ 8.19万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

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.

左右肢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肢体有节奏的基本运动模式是由位于脊髓内的神经网络产生的。在这项研究中，我们重点揭示了参与左/右协调的回路的神经机制及其在发育过程中的功能分化。在分离的新生大鼠脊髓标本中，灌流5-羟色胺等神经活性物质可引起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呈现交替模式，在阻断甘氨酸能抑制性突触传递后，这种节律性活动转变为同步模式。然而，在胎儿早期协调节律活动开始的时候，可以观察到左右两侧之间的同步模式，直到它们在出生前变成交替模式。阻断GABA_A受体可破坏这一同步模式，GABA_A受体在此期间介导兴奋性突触传递。在切断新生儿和胎儿脊髓的腹连合后，两侧之间的这种协调活动消失，这表明左右交替所必需的CIN仅限于脊髓的腹侧区域，并将轴突投射到腹连合处。逆行追踪定位于脊髓腹内侧区的一组不同的CIN。此外，我们还发现，这些CIN具有与运动神经元活动相对应的节律性活动，这清楚地表明了这些神经元在产前发育过程中参与了运动回路和脊髓CPG。