Novel functions of GABA signaling in adult neurogenesis

Neurotransmitter gamma-aminobutiric acid (GABA) through ionotropic GABA_A and metabotropic GABA_B receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells (NSCs/NPCs). The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na⁺/K⁺/2Cl^- co-transporter NKCC1 driving Cl^- influx and neuron-specific K⁺/Cl^- co-transporter KCC2 driving Cl^- efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 (DISC1) and brain-derived neurotrophic factor (BDNF) signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and newborn neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.