Acceleration of axonal regeneration by GABA/Gly excitation.

In the mature central nervous system (CNS), γ-aminobutyric acid (GABA) and glycine (Gly) are predominant inhibitory neurotransmitters that negatively regulate neural activities. In contrast, GABA mediates membrane potential depolarization during development, and GABA/Gly become excitatory after nerve injury because of the high intracellular Cl concentration induced by low expression of K, Cl cotransporter 2 (KCC2), which transports Cl out of neurons. Many studies have reported that during CNS development, GABAergic excitatory action might play crucial roles in neurogenesis through Ca influx. Nevertheless, its involvement in neurogenesis has not been proven because the CNS can develop normally without GABAergic signals. Recently, two research groups demonstrated that low level of KCC2 (i.e., GABA/Gly excitation) after nerve injury is involved in axonal regeneration and in enhancement of functional recovery. In this manuscript, we review GABA/Gly excitation and introduce recent findings describing its involvement in axonal regeneration.