RT Journal Article
SR Electronic
T1 Interaction between the Corticotropin-Releasing Factor System and Hypocretins (Orexins): A Novel Circuit Mediating Stress Response
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 11439
OP 11448
DO 10.1523/JNEUROSCI.3459-04.2004
VO 24
IS 50
A1 Raphaëlle Winsky-Sommerer
A1 Akihiro Yamanaka
A1 Sabrina Diano
A1 Erzsebet Borok
A1 Amanda J. Roberts
A1 Takeshi Sakurai
A1 Thomas S. Kilduff
A1 Tamas L. Horvath
A1 Luis de Lecea
YR 2004
UL http://www.jneurosci.org/content/24/50/11439.abstract
AB 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.