Department of Biology and Wildlife, University of Alaska Fairbanks, Fairbanks, AK, USA.
Adv Exp Med Biol. 2010;669:109-13. doi: 10.1007/978-1-4419-5692-7_22.
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 CO(2). 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.
下丘脑外侧神经元释放的食欲肽（orexins）对觉醒状态、体温调节、进食行为有重要贡献，最近还被提出在呼吸和中枢化学敏感性中发挥作用。使用原位动脉灌注幼鼠制备，我们确定了食欲肽-1（hcrt-1）和 SB-408124（食欲肽受体亚型 1 的拮抗剂，hcrt-r1）对膈神经活动的影响，膈神经活动是呼吸（神经通气）的神经相关物，以及对 CO2 的神经通气敏感性。通过灌流液应用 hcrt-1 对基础放电几乎没有影响。然而，阻断 hcrt-r1 可防止与高碳酸血症相关的正常膈神经爆发频率反应。这些数据表明内源性食欲肽能调制增强神经通气化学敏感性。使用体外延髓切片制备进行的进一步研究探讨了 hcrt-1 对舌下神经活动的影响，舌下神经活动是体外通气的相关物。外源性 hcrt-1 的应用未能显著改变新生大鼠切片中舌下神经爆发输出，表明该神经通气回路的这一部分对 hcrt-1 不敏感。总之，这些数据表明 hcrt-1 是中枢化学敏感性的调节剂。
