Differentiation of Central Pattern Generators in the rat.

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The rhythmic motor activity involved in locomotion is generally considered to be generated by interneuronal networks within the spinal cord. Developmental changes in the 5-HT-induced locomotor rhythm were examined in isolated spinal cord preparations taken from fetal rats. Motor activity was recorded from L2/L3 and L5 ventral roots, representing activity in flexors and extensors, respectively. Bath application of 5-HT evoked rhythmic bursts that were synchronized in all ventral roots studied at E16.5. At E18.5, 5-HT evoked rhythmic bursts that alternated between the two sides, while the bursts in the L2/L3 ventral root were synchronous with those in the ipsilateral L5 ventral root. At E20.5, 5-HT evoked alternate rhythmic bursts in L2/L3 and L5 ventral roots. In the presence of strychnine, 5-HT induced rhythmic bursts that were synchronized in all ventral roots studied at E18.5 and E20.5, suggesting that the change in the pattern of rhythmic motor activity that occurs with age is due to the development of glycine-mediated inhibition.In preparations from fetuses at the earlier stages (E14.5 - E16.5), we observed 5-HT evoked rhythmic bursts , which were synchronized on the two sides in the corresponding ventral roots. These rhythmic bursts were not blocked by kynurenate, the glutamate receptor blocker, though it was completely abolished by strychnine, the glycine receptor antagonist. A brief application of glycine evoked excitatory responses in the ventral roots. It is concluded that glycine functions transiently as excitatory transmitters at these stages.These results suggest that functional change in glycine-induced responses during development plays an important role in differentiation of the neuronal circuits generating locomotion.