Brown T M, Coogan A N, Cutler D J, Hughes A T, Piggins H D
Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK.
Neurosci Lett. 2008 Dec 31;448(3):273-8. doi: 10.1016/j.neulet.2008.10.058. Epub 2008 Nov 1.
The study of neural arousal mechanisms has been greatly aided by the discovery of the orexin peptides (orexin A and orexin B), the subsequent identification of the neurons that synthesize these peptides, their projections in the brain, and the distribution of orexin receptors in the central nervous system. Orexin neuron activation is partly controlled by circadian signals generated in the brain's main circadian pacemaker, the suprachiasmatic nuclei (SCN). The SCN clock is in turn reset by arousal-promoting stimuli and, intriguingly, orexin fibers and receptor expression are detected in the SCN region. It is unclear, however, if orexin can alter SCN neuronal activity. Here using a coronal brain slice preparation, we found that orexin A and orexin B (0.1-1 microM) elicited significant changes in the extracellularly recorded firing rate and firing pattern in approximately 80% of rat SCN cells tested; the most common response was suppression of firing rate. Co-application of orexin A with a cocktail of ionotropic GABA and glutamate receptor antagonists did not alter the actions of this peptide on firing rate, but did change some its effects on firing pattern. We conclude that orexins can alter SCN neurophysiology and may influence the transmission of information through the SCN to other CNS regions.
食欲肽（食欲肽A和食欲肽B）的发现、随后对合成这些肽的神经元的鉴定、它们在大脑中的投射以及食欲肽受体在中枢神经系统中的分布，极大地促进了对神经唤醒机制的研究。食欲肽神经元的激活部分受大脑主要昼夜节律起搏器视交叉上核（SCN）产生的昼夜节律信号控制。反过来，SCN时钟又由促进唤醒的刺激重置，有趣的是，在SCN区域检测到食欲肽纤维和受体表达。然而，尚不清楚食欲肽是否能改变SCN神经元的活动。在这里，我们使用冠状脑片制备方法发现，食欲肽A和食欲肽B（0.1-1 microM）在大约80%的受试大鼠SCN细胞中引起细胞外记录的放电率和放电模式的显著变化；最常见的反应是放电率的抑制。将食欲肽A与离子型GABA和谷氨酸受体拮抗剂混合使用，不会改变该肽对放电率的作用，但会改变其对放电模式的一些影响。我们得出结论，食欲肽可以改变SCN神经生理学，并可能影响通过SCN向其他中枢神经系统区域的信息传递。
