Uncovering a neural circuit controlling adult quiescent neural stem cell activation in the subventricular zone

Abstract

SummaryThe maintenance and differentiation of the adult neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. How neurogenesis in the SVZ is regulated by neural circuit activity remains poorly understood. Here we identified a novel neural circuit that regulates the state of lateral ventricular wall (LV) NSCs. Our results demonstrate that direct glutamatergic inputs from the frontal cortex, as well as local inhibitory interneurons, control the activity of subependymal cholinergic neurons. In vivo optogenetic and chemogenetic stimulation of defined neuronal populations within this circuit were sufficient to control LV NSC proliferation and SVZ neurogenesis. Moreover, acetylcholine (Ach), which activates M1 muscarinic ACh receptors, triggers the activation of quiescent NSCs. These findings shed light on neural activity-dependent regulation of postnatal and adult LV NSCs activation and SVZ neurogenesis.