The injection of hypocretin-1 into the nucleus pontis oralis induces either active sleep or wakefulness depending on the behavioral state when it is administered.

作者: Mingchu Xi , Michael H. Chase

DOI: 10.1093/SLEEP/33.9.1236

关键词: Sleep in non-human animalsCataplexyFacilitationWakefulnessMuscle toneTegmentumNeurosciencePsychologyExcitatory postsynaptic potentialNeuropeptide

摘要: HYPOCRETIN-1 AND HYPOCRETIN-2 (ALSO KNOWN AS OREXIN-A OREXIN-B) ARE 2 NEUROPEPTIDES THAT SYNTHESIZED BY A WELL-DEFINED GROUP of neurons that are located in the lateral hypothalamus.1–3 deficiency functioning hypocretinergic system results narcolepsy with cataplexy, which is characterized by a sudden loss muscle tone (i.e., cataplexy) triggered unexpected, strong emotional events humans, dogs, and other species even though subjects remain awake.4–7 The data suggest plays crucial role regulation not only wakefulness motor facilitation, but also active (REM) sleep its accompanying patterns inhibition. The nucleus pontis oralis (NPO) pontine tegmentum key generation (AS) as well wakefulness.8–12 Anatomic studies have shown both hypocretin receptor-1 receptor-2 present NPO within innervated rich plexus fibers.13–16 We reported microinjections either hypocretin-1 or hypocretin-2 into induce, short latency, behavioral state comparable to naturally occurring AS.17,18 In addition, we juxtacellular application (which has high affinity for receptor-2) onto an increase discharge evoked spontaneous excitatory synaptic activity neurons.17,19 These cells putative effector comprise active-sleep generator.8 indicate processes involved critical site action respect control this state. On hand, recent from laboratories injections result extended periods wakefulness, rather than inducement AS.20,21 Consequently, hypothesized these “apparently” paradoxical findings due fact was administered during different states sets studies. This hypothesis based upon related state-dependent data, were initially thought be “discrepant,” revealed stimuli occur although identical stimuli, when applied AS, promote profound inhibition. phenomenon named reticular response-reversal.22 Accordingly, study, compared, chronically instrumented unanesthetized cats, followed microinjection hypoctretin-1 while animals awake arose injected quiet (QS).

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