RT Journal Article
SR Electronic
T1 Basal forebrain cholinergic circuits orchestrate diverse cell types in the adult dentate gyrus to support neural stem cell function and spatial memory
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.25.493227
DO 10.1101/2022.05.25.493227
A1 Luis Quintanilla
A1 Yijing Su
A1 Jeremy M. Simon
A1 Yan-Jia Luo
A1 Brent Asrican
A1 Seth Tart
A1 Ryan N. Sheehy
A1 Ya-Dong Li
A1 Guo-li Ming
A1 Hongjun Song
A1 Juan Song
YR 2022
UL http://biorxiv.org/content/early/2022/05/27/2022.05.25.493227.abstract
AB Dentate gyrus (DG) is a critical structure involved in spatial memory and adult neurogenesis, two distinct processes dynamically regulated by local circuits comprising diverse populations of DG cells. It remains unknown how these DG cells are orchestrated to regulate these distinct hippocampal functions. Here we report activation of a cholinergic circuit from the Diagonal Band of Broca to DG promotes quiescent radial neural stem cell (rNSC) activation and spatial memory. Furthermore, single-nucleus RNA-sequencing reveals broad transcriptomic changes across DG mature and adult-born cells in response to cholinergic-circuit activation. Notably, neuronal populations exhibit cholinergic-activity-induced molecular changes related to synaptic functions crucial for spatial memory; while rNSCs exhibit changes related to structural remodeling and neurogenic proliferation crucial for hippocampal neurogenesis. Electrophysiology and NicheNet analyses reveal granule cells, endothelial cells, and astrocytes as potential intermediaries for cholinergic regulation of rNSCs. Our findings reveal cell-type-specific signaling mechanisms underlying cholinergic regulation of distinct DG functions.Competing Interest StatementThe authors have declared no competing interest.