Control of neural stem cell proliferation and lineage progression in the postnatal subventricular zone by GABAergic signaling

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The subventricular zone (SVZ) is the major neurogenic region of the postnatal mammalian brain, where stem cells continue to generate new neurons throughout adulthood. Recent evidence suggests that γ-aminobutyric acid (GABA) directly controls proliferation, differentiation and migration of precursors in the postnatal SVZ by activating GABAA receptors (GABAARs). However, which cell types are affected is not clear and the mechanisms underlying these effects are still unknown.We here propose to use lentiviral mediated cell tagging to further investigate the functional role of GABAergic signalling on stem cells and their progeny in their intact niche and elucidate the mechanisms involved. We will also investigate the existence of paracrine/autocrine feedback mechanisms in the neurogenic niche by analysing the contribution of the various precursor types to the regulation of GABA concentration in the extracellular space. In addition, by specifically modulating GABAAR signalling in vivo we will investigate the role of endogenous GABA on neurogenesis in the postnatal SVZ.This analysis will clarify the role of GABAAR signalling in the regulation of adult stem cell proliferation. It will also have potential implication for the therapy of neurological disorders involving administration of GABAARs modulators.