期刊
JOURNAL OF NEUROSCIENCE
卷 24, 期 50, 页码 11439-11448出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3459-04.2004
关键词
hypocretin; orexin; corticotropin-releasing factor; hypothalamus; stress; homeostasis
资金
- NCRR NIH HHS [RR014451, R01 RR014451] Funding Source: Medline
- NIAAA NIH HHS [R21AA13241] Funding Source: Medline
- NIDDK NIH HHS [DK060711, R01 DK060711] Funding Source: Medline
- NIMH NIH HHS [MH58543, R01 MH061755-03, R01 MH061755-05, MH61755, MH059847, R01 MH061755-06, R01 MH058543, R01 MH061755, R01 MH059847, R01 MH061755-04] Funding Source: Medline
The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. We tested whether the hypocretinergic system is a critical component of the stress response activated by the corticotropin-releasing factor (CRF). Our results show that CRF-immunoreactive terminals make direct contact with hypocretin-expressing neurons in the lateral hypothalamus and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. We also demonstrate that application of CRF to hypothalamic slices containing identified hypocretin neurons depolarizes membrane potential and increases firing rate in a subpopulation of hypocretinergic cells. CRF-induced depolarization was tetrodotoxin insensitive and was blocked by the peptidergic CRF-R1 antagonist astressin. Moreover, activation of hypocretinergic neurons in response to acute stress was severely impaired in CRF-R1 knock-out mice. Together, our data provide evidence of a direct neuroanatomical and physiological input from CRF peptidergic system onto hypocretin neurons. We propose that, after stressor stimuli, CRF stimulates the release of hypocretins and that this circuit contributes to activation and maintenance of arousal associated with the stress response.
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