Frontal cortical regulation of neurogenesis and cellular proliferation in the ventral subventricular zone

Abstract

Neurogenesis and differentiation of the neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. Here we identified a novel circuit that regulates neurogenesis and cellular proliferation in the lateral ventricle SVZ (LV-SVZ). Our results demonstrate direct glutamatergic inputs from the frontal cortex as well as local inhibitory interneurons, control the activity of distinctive cholinergic neurons in the subependymal zone (subep-ChAT+). In vivo optogenetic stimulation and inhibition in this circuit were sufficient to control local SVZ neurogenesis, LV NSCs proliferation, and SVZ cellular divisions in ventral SVZ. These findings shed light on local and distal neural circuit activity-dependent regulation of postnatal and adult SVZ neurogenesis and LV-SVZ cellular proliferation.