This article was published online on 6 January 2010. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 11 January 2010.
Cholinergic activation of hippocampal neural stem cells in aged dentate gyrus†
Version of Record online: 6 JAN 2010
Copyright © 2009 Wiley-Liss, Inc.
Volume 21, Issue 4, pages 446–459, April 2011
How to Cite
Itou, Y., Nochi, R., Kuribayashi, H., Saito, Y. and Hisatsune, T. (2011), Cholinergic activation of hippocampal neural stem cells in aged dentate gyrus. Hippocampus, 21: 446–459. doi: 10.1002/hipo.20761
- Issue online: 6 JAN 2010
- Version of Record online: 6 JAN 2010
- Manuscript Accepted: 18 NOV 2009
- The Ministry of Education, Culture, Sports, Science, and Technology of Japan. Grant Number: 19208030
- calcium imaging;
Adult hippocampal neurogenesis contributes to the hippocampal circuit's role in cognitive functioning. New neurons are generated from hippocampal neural stem cells (NSCs) throughout life, but their generation is substantially diminished in aged animals due to a decrease in NSC proliferation. Because acetylcholine (ACh) is an important neurotransmitter released in the hippocampus during learning and exercise that is known to decrease with aging, we investigated whether aged NSCs can respond to ACh. In this study, we found that cholinergic stimulation has a positive effect on NSC proliferation in both young adult (8–12 weeks old) and aged mice (>2 years old). In fresh hippocampal slices, we observed a rapid calcium increase in NSCs in the dentate gyrus after muscarinic cholinergic stimulation, in both age groups. Furthermore, we found that the exercise-induced promotion of aged NSC proliferation was abrogated by the specific lesioning of the septal cholinergic system. In turn, cholinergic activation by either eserine (physostigmine) or donepezil treatment promoted the proliferation of NSCs in aged mice. These results indicate that NSCs respond to cholinergic stimulation by proliferating in aged animals. Physiological and/or pharmacological cholinergic stimulation(s) may ameliorate cognitive decline in aged animals, by supporting adult hippocampal neurogenesis. © 2010 Wiley-Liss, Inc.