Modulation of Respiratory Activity by Hypocretin-1 (Orexin A) In Situ and In Vitro

  • Andrea Corcoran
  • George Richerson
  • Michael Harris
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 669)


Release of hypocretins (orexins) by neurons in the lateral hypothalamus is an important contributor to arousal state, thermoregulation, feeding behavior, and has recently been proposed to play a role in breathing and central chemosensitivity. Using the in situ arterially perfused juvenile rat preparation, we determined the effect of hypocretin-1 (hcrt-1) and SB-408124 (antagonist for hypocretin receptor subtype 1, hcrt-r1) on phrenic nerve activity, a neural correlate of breathing (neuroventilation), and the neuroventilatory sensitivity to CO2. Application of hcrt-1 through the perfusate had little effect on baseline firing. Blocking hcrt-r1, however, prevented the phrenic burst frequency response normally associated with hypercapnia. These data suggest that endogenous hypocretinergic modulation enhances neuroventilatory chemosensitivity. Further studies using the in vitro medullary slice preparation explored the effect of hcrt-1 on hypoglossal nerve activity, a correlate of ventilation in vitro. Application of exogenous hcrt-1 failed to significantly alter hypoglossal burst output in neonatal rat slices, indicating that this portion of the neuroventilatory circuit is insensitive to hcrt-1. Taken together, these data suggest that hcrt-1 is a modulator of central chemosensitivity.


Burst Frequency Burst Amplitude Central Chemoreceptor Phrenic Nerve Activity Hcrt Neuron 
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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Andrea Corcoran
    • 1
  • George Richerson
    • 2
    • 3
  • Michael Harris
    • 1
  1. 1.Department of Biology and WildlifeUniversity of Alaska FairbanksFairbanksUSA
  2. 2.Department of NeurologyYale UniversityNew HavenUSA
  3. 3.Veterans Affairs Medical CenterWest HavenUSA

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