Abstract
Roles of afferents activity on the development of neural circuits has been intensely studied on the sensory system. In contrast to a number of studies regarding the influence of peripheral inputs on excitatory circuits development, less is known on its action on inhibitory circuits development. Recent studies demonstrates that the main inhibitory transmitters in the CNS, GABA and glycine, play as excitatory substances and promote various neuronal development. Actions of GABA/glycine change from a depolarization to a hyperpolarization with age, resulted from developmental upregulation of KCC2 in expression and function, a main molecule extruding intracellular chloride out of neurons, and a decrease of intracellular chloride concentration. This switch was regulated by afferent activity during development. Even after maturation, neuronal insults, e.g. injury, induced a down-regulation of KCC2 in expression, resulting in an increase intracellular chloride concentration and GABA-induced excitation. Re-acquisition of immature characteristics following injury was also well demonstrated in the excitatory transmitter. For example, in injured neurons the subunits making up NMDA receptor changed from predominantly NR2A to other type subunits, resulting in less sensitivity to extracellular magnesium ion and prolonged decay time of NMDA currents, which are characterized in immature neurons. If developmental strategy were the case in the regeneration, sensory afferent activity might largely regulates the remodeling of the neurotransmitter function in regeneration. [Jpn J Physiol 54 Suppl:S44 (2004)]
