Neuromodulation and developmental plasticity in the locomotor system of anuran amphibians during metamorphosis

Keith Thomas Sillar, D Combes, S Ramanathan, M Molinari, AJ Simmers

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)


Metamorphosis in frogs has long fascinated laymen and scientists alike. This remarkable developmental transformation involves the simultaneous remodelling of almost every organ in the body, including the gut, associated with a switch in diet from filter feeder to predator, and the visual system, from laterally-directed monocular to forward-directed binocular vision. In the context of locomotion there is the complete loss of the tail, the main structure involved in generating thrust during swimming in larvae, and the gain of the limbs which produce rhythmic extension-flexion kicks during swimming and jumping.

Here we review recent evidence from experiments utilizing novel in vitro isolated preparations of the Xenopus laevis spinal cord and brainstem which remain viable for several days and can generate motor rhythms similar to those that would normally drive locomotion in vivo. The results indicate that the developing limb circuitry is born from within the existing axial-based network, which acts like a functional scaffold. Initially the limb activity shares the same left-right alternation coordination and relatively high frequency as the tail swimming network. Only later, once the limbs are fully functional, does the limb network break free to produce left-right synchrony of limb motoneuron bursting and with a different, slower cadence than the tail-based system. During the initial formation of the limb networks nitric oxide-producing neurons appear in the spinal cord, but occupy regions other than those in which the new limb circuitry is developing. Now exogenous nitric oxide facilitates locomotor activity, in contrast to its inhibitory effects on swimming at earlier larval stages of development. (c) 2007 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)94-102
Number of pages9
JournalBrain Research Reviews
Issue number1
Publication statusPublished - Jan 2008


  • amphibian
  • development
  • metamorphosis
  • locomotion
  • spinal networks
  • neuromodulation
  • nitric oxide
  • FROG


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