Regulation of adult neurogenesis by GABAergic transmission: signaling beyond GABA(A)-receptors

In the adult mammalian brain, neurogenesis occurs in the olfactory bulb (OB) and in the dentate gyrus (DG) of the hippocampus. Several studies have shown that multiple stages of neurogenesis are regulated by GABAergic transmission with precise spatio-temporal selectivity, and involving mechanisms common to both systems or specific only to one. In the subgranular zone (SGZ) of the DG, GABA neurotransmitter, released by a specific population of interneurons, regulates stem cell quiescence and neuronal cell fate decisions. Similarly, in the subventricular zone (SVZ), OB neuroblast production is modulated by ambient GABA. Ambient GABA, acting on extrasynaptic GABA(A) receptors (GABA(A)R), is also crucial for proper adult-born granule cell (GC) maturation and synaptic integration in the OB as well as in the DG. Throughout adult-born neuron development, various GABA receptors and receptor subunits play specific roles. Previous work has demonstrated that adult-born GCs in both the OB and the DG show a time window of increased plasticity in which adult-born cells are more prone to modification by external stimuli. One mechanism that controls this “critical period” is GABAergic modulation. Indeed, depleting the main phasic GABAergic inputs in adult-born neurons results in dramatic effects, such as reduction of spine density and dendritic branching in adult-born OB GCs. In this review, we systematically compare the role of GABAergic transmission in the regulation of adult neurogenesis between the OB and the hippocampus, focusing on the role of GABA in modulating plasticity and critical periods of adult-born neuron development. Finally, we discuss signaling pathways that might mediate some of the deficits observed upon targeted deletion of postsynaptic GABA(A)Rs in adult-born neurons.