Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 17, Pages E3526-E3535Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1614552114
Keywords
sleep; narcolepsy; orexin; serotonin; amygdala
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [24390052, 16H05120, 23659134]
- Astellas Foundation for Research on Metabolic Disorders
- Brain Science Foundation
- JSPS Research Fellowship for Young Scientists
- Deutsche Forschungsgemeinschaft [MA 4692/3-1, He2471/18-1, SPP1926, SFB874]
- Grants-in-Aid for Scientific Research [16H05120, 16H06401, 16H06400, 15K01832, 23659134, 15H03122, 16H01608] Funding Source: KAKEN
Ask authors/readers for more resources
Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paperwe show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available