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The Journal of Neuroscience, December 1, 2002, 22(23):10388-10398

Basis of Changes in Left-Right Coordination of Rhythmic Motor Activity during Development in the Rat Spinal Cord

Kiyomi Nakayama1, 2, Hiroshi Nishimaru1, and Norio Kudo1

1 Department of Physiology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, and 2 Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, Ami, Ibaraki 300-0394, Japan

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 GABAA receptors. When the pattern of rhythmic activity became left-right alternate at later fetal stages, these connections, still via GABAA 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.

Key words: GABAA receptor; commissural neuron; locomotion; development; spinal cord; rat fetus; imaging


Copyright © 2002 Society for Neuroscience  0270-6474/02/222310388-11$05.00/0


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