WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, October 1, 2008, 28(40):10167-10184; doi:10.1523/JNEUROSCI.1809-08.2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Web of Science (2)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cano, G.
Right arrow Articles by Saper, C. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cano, G.
Right arrow Articles by Saper, C. B.

 Previous Article

Behavioral/Systems/Cognitive
Neural Circuitry of Stress-Induced Insomnia in Rats

Georgina Cano, Takatoshi Mochizuki, and Clifford B. Saper

Department of Neurology, Beth Israel Deaconess Medical Center, Division of Sleep Medicine and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02215

Correspondence should be addressed to Clifford B. Saper, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Email: csaper{at}bidmc.harvard.edu

Sleep architecture is often disturbed after a stressful event; nevertheless, little is known about the brain circuitry responsible for the sleep perturbations induced by stress. We exposed rats to a psychological stressor (cage exchange) that initially causes an acute stress response, but several hours later generates a pattern of sleep disturbances similar to that observed in stress-induced insomnia in humans: increased sleep latency, decreased non-REM (nREM) and REM sleep, increased fragmentation, and high-frequency EEG activity during nREM sleep. We examined the pattern of Fos expression to identify the brain circuitry activated, and found increased Fos in the cerebral cortex, limbic system, and parts of the arousal and autonomic systems. Surprisingly, there was simultaneous activation of the sleep-promoting areas, most likely driven by ongoing circadian and homeostatic pressure. The activity in the cerebral cortex and arousal system while sleeping generates a novel intermediate state characterized by EEG high-frequency activity, distinctive of waking, during nREM sleep. Inactivation of discrete limbic and arousal regions allowed the recovery of specific sleep components and altered the Fos pattern, suggesting a hierarchical organization of limbic areas that in turn activate the arousal system and subsequently the cerebral cortex, generating the high-frequency activity. This high-frequency activity during nREM was eliminated in the stressed rats after inactivating parts of the arousal system. These results suggest that shutting down the residual activity of the limbic-arousal system might be a better approach to treat stress-induced insomnia, rather than potentiation of the sleep system, which remains fully active.

Key words: stress; sleep disturbances; insomnia; rat model; Fos; arousal system; limbic system

Received April 24, 2008; revised July 16, 2008; accepted Aug. 13, 2008.

Correspondence should be addressed to Clifford B. Saper, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Email: csaper{at}bidmc.harvard.edu






-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-