| First Author | Otto SL | Year | 2019 |
| Journal | Brain Struct Funct | Volume | 224 |
| Issue | 2 | Pages | 829-846 |
| PubMed ID | 30515567 | Mgi Jnum | J:318541 |
| Mgi Id | MGI:6860076 | Doi | 10.1007/s00429-018-1799-6 |
| Citation | Otto SL, et al. (2019) The alpha7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion. Brain Struct Funct 224(2):829-846 |
| abstractText | Disruption in cholinergic signaling has been linked to many environmental and/or pathological conditions known to modify adult neurogenesis. The alpha7 nAChRs are in the family of cys-loop receptor channels which have been shown to be neuroprotective in adult neurons and are thought to be critical for survival and integration of immature neurons. However, in developing neurons, poor calcium buffering may cause alpha7 nAChR activation to be neurotoxic. To investigate whether the alpha7 nAChR regulates neurogenesis in the hippocampus, we used a combination of mouse genetics and imaging to quantify neural stem cell (NSC) densities located in the dentate gyrus of adult mice. In addition, we considered whether the loss of alpha7 nAChRs had functional consequences on a spatial discrimination task that is thought to rely on pattern separation mechanisms. We found that the loss of alpha7 nAChRs resulted in increased neurogenesis in male mice only, while female mice showed increased cell divisions and intermediate progenitors but no change in neurogenesis. Knocking out the alpha7 nAChR from nestin(+) NSCs and their progeny showed signaling in these cells contributes to regulating neurogenesis. In addition, male, but not female, mice lacking alpha7 nAChRs performed significantly worse in the spatial discrimination task. This task was sexually dimorphic in wild-type mice, but not in the absence of alpha7 nAChRs. We conclude that alpha7 nAChRs regulate adult neurogenesis and impact spatial discrimination function in male, but not female mice, via a mechanism involving nestin(+) NSCs and their progeny. |
