Regulation of proliferation and AQP4 expression in adult neural precursor by GABAAR

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The lateral subependymal zone (SEZ) represents the main neurogenic niche in the adult murine brain. In this region the neurotransmitter gamma-aminobutyric acid (GABA) modulates the proliferation of both neural stem cells (NSCs) and their progeny. However, the outcome of this regulation on adult NSCs and the mechanisms involved are still debated. We have previously shown that in the neonatal SEZ GABAA receptor (GabaAr) activation induces osmotic swelling of NSCs by promoting Cl- influx as well as an increase in the expression of the Aquaporin (Aqp) 4 at the cell membrane. In the neonatal SEZ this leads to NSC activation and proliferation. We here propose to investigate whether GABA similarly affects adult NSCs and the contribution of the regulation of Aqp4 on the effect of the neurotransmitter on adult NSC proliferation. We will also examine the molecular mechanisms underlying the GABAergic regulation of Aqp4 expression. As we found that GabaAr function affects water exchange between the lateral ventricle and the germinal niche, the proposed project may provide new insights relevant not only to NSC proliferation but also to water exchange dynamics in the central nervous system.