Live imaging of neurogenesis in the adult mouse hippocampus

Abstract

Neural stem/progenitor cells (NSPCs) generate neurons throughout life in the mammalian hippocampus. We used chronic in vivo imaging and followed genetically labeled individual NSPCs and their progeny in the mouse hippocampus for up to 2 months. We show that NSPCs targeted by the endogenous Achaete-scute homolog 1 (Ascl1)-promoter undergo limited rounds of symmetric and asymmetric divisions, eliciting a burst of neurogenic activity, after which they are lost. Further, our data reveal unexpected asymmetric divisions of non-radial glia-like NSPCs. Cell fates of Ascl1-labeled lineages suggest a sequential transition from a proliferative to a neurogenic phase, reminiscent of a developmental-like program. By providing a comprehensive description of lineage-relationships, from dividing NSPCs to newborn neurons integrating into the hippocampal circuitry, our data provide insight into how NSPCs support life-long hippocampal neurogenesis.