During adulthood, new neurons are generated by so called adult neurogenesis in the subgranular zone (SGZ) of the hippocampus and in the subventricular zone (SVZ) of the lateral ventricles. In these neurogenic niches, the adult neural stem cells (aNSCs) generate new neurons that are critical for establishing factual memories and mood control. Regulation of aNSCs is critical for cognitive brain functions and for development of future cell-based therapies of neurodegenerative diseases. While genetic and paracrine regulation of aNSCs have been studied extensively, the nature of molecular sensors detecting changes in their microenvironment is unknown. Pilot genome and functional analyses presented in this proposal show that the epithelial sodium channel (ENaC) may serve as a candidate for such sensor in aNSCs. ENaC is found to be enriched in aNSCs over other sorted cell types from the brain and blocking ENaC impairs aNSCs. This proposal combines electrophysiology, live-cell imaging, genome screening and transgenic mouse technology to address two fundamental questions. First, can ENaC act as molecular sensors for aNSCs detecting environmental changes in the niche? Second, how are SVZ and hippocampal aNSCs differentially regulated by ENaC? The proposed experiments embody the call for the transfer of knowledge and the need for competitiveness on both intellectual and technical levels. The host laboratory belongs to world leaders in SVZ neurogenesis and has demonstrated technical prowess by developing new techniques such as the cell-clone analysis by long-term live imaging. The proposing researcher is an expert in SGZ neurogenesis and brings his electrophysiological expertise from the USA to the European host lab. This proposal thus aims to open new research venues for the field of adult neurogenesis by combining technical and innovative capacities of the host lab with the unique skill set and expertise of the proposing researcher.