Govindaiah G, Cox Charles L
Department of Molecular and Integrative Physiology, University of Illinois, Urbana, IL 61801, USA.
Neuropharmacology. 2006 Sep;51(3):414-25. doi: 10.1016/j.neuropharm.2006.03.030. Epub 2006 May 19.
Orexins (hypocretins) are peptides of hypothalamic origin that play an important role in maintaining wakefulness. Reduced orexin levels have been associated with an increased incidence of narcolepsy. Considering thalamic nuclei are interconnected with virtually all neocortical regions and the thalamus has been found to produce distinct activities related to different levels of arousal, we have examined the actions of orexins on thalamic neurons using an in vitro thalamic slice preparation. The orexins (orexin-A and orexin-B) produced distinct actions within different intralaminar nuclei. Orexin-B strongly depolarized the majority of centrolateral nucleus (CL) neurons (71%), but depolarized a significantly smaller population of parafascicular nuclei (Pf) neurons (10%). In the mediodorsal thalamic nucleus (MD), orexin-B depolarized 21% of the neurons tested. Overall, orexin-B was found to be more potent than Orexin-A. Orexin-A depolarized a significantly smaller population of CL neurons (23%), but had no effect on Pf neurons. In addition, orexin-A produced a small depolarization in 28% of neurons in the thalamic reticular nucleus (TRN). Both orexin-A and orexin-B had no effect on neurons in the lateral posterior (LP), lateralodorsal (LD), posterior thalamic (Po), ventrobasal (VB) nucleus and lateral geniculate nucleus (LGN). The depolarizing actions of orexins were sufficient to alter the firing mode of these neurons from a burst- to tonic-firing mode. The excitatory actions of orexin-B result from a decrease in the apparent leak potassium current (Kleak). The orexin-B mediated excitation was also attenuated by bupivacaine suggesting the involvement of Kleak current. Further, the actions of orexin-B were occluded by the classical neurotransmitter dopamine, indicating the orexins may share similar ionic mechanisms. Thus, the depolarizing actions of orexins may play a key role in altering the firing mode of thalamic neurons associated with different states of consciousness.
食欲素（下丘脑泌素）是源自下丘脑的肽类，在维持清醒状态中起重要作用。食欲素水平降低与发作性睡病发病率增加有关。鉴于丘脑核与几乎所有新皮层区域相互连接，且已发现丘脑会产生与不同觉醒水平相关的独特活动，我们使用体外丘脑切片制备方法研究了食欲素对丘脑神经元的作用。食欲素（食欲素 -A 和食欲素 -B）在不同的板内核中产生了不同的作用。食欲素 -B 使大多数中央外侧核（CL）神经元（71%）强烈去极化，但使束旁核（Pf）神经元中数量明显较少的一部分（10%）去极化。在丘脑背内侧核（MD）中，食欲素 -B 使 21% 的受试神经元去极化。总体而言，发现食欲素 -B 比食欲素 -A 更有效。食欲素 -A 使数量明显较少的一部分 CL 神经元（23%）去极化，但对 Pf 神经元没有影响。此外，食欲素 -A 使丘脑网状核（TRN）中 28% 的神经元产生小幅度去极化。食欲素 -A 和食欲素 -B 对外侧后核（LP）、背外侧核（LD）、丘脑后核（Po）、腹侧基底核（VB）和外侧膝状体核（LGN）中的神经元均无影响。食欲素的去极化作用足以将这些神经元的放电模式从爆发式放电模式转变为紧张性放电模式。食欲素 -B 的兴奋作用源于表观漏钾电流（Kleak）的减少。布比卡因也减弱了食欲素 -B 介导的兴奋，提示 Kleak 电流参与其中。此外，食欲素 -B 的作用被经典神经递质多巴胺阻断，表明食欲素可能共享相似的离子机制。因此，食欲素的去极化作用可能在改变与不同意识状态相关的丘脑神经元放电模式中起关键作用。
