Stimulation of the muscarinic receptor M4 regulates neural precursor cell proliferation and promotes adult hippocampal neurogenesis

• DOI: 10.1242/dev.201835
• Publication Date: 2023-12-08T14:34:36Z
• Authors: Lidia I. Madrid; Katelyn Hafey; Saurabh Bandhavkar; Gabriela O. Bodea; Javier Jimenez-Ma...; Michael Milne; Tara L. Walker; Geoffrey J. Faulkner; Elizabeth J. Coulson; Dhanisha J. Jhaveri

Cholinergic signaling plays a crucial role in the regulation of adult hippocampal neurogenesis; however, mechanisms by which acetylcholine mediates neurogenic effects are not completely understood. Here, we report expression muscarinic receptor subtype M4 (M4 mAChR) on subpopulation neural precursor cells (NPCs) mouse hippocampus, and demonstrate that its pharmacological stimulation promotes their proliferation, thereby enhancing production new neurons vivo. Using targeted ablation approach, also show medial septum (MS) diagonal band Broca (DBB) cholinergic support both survival morphological maturation adult-born hippocampus. Although systemic administration an M4-selective allosteric potentiator fails to fully rescue MS/DBB lesion-induced decrease neurogenesis, it further exacerbates impairment neurons. Collectively, these findings reveal stage-specific roles mAChRs regulating uncoupling positive from M4-induced inhibition maturation, at least context dysfunction.