In this review, we first discuss the basic biological features of orexins and their receptors, and we then describe the neuronal inputs and outputs of the orexin neurons. Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei. Studies have shown that one of sleep's underlying functions is to replenish this glycogen energy source. Organization of cerebral cortical afferent systems in the rat. Mu agonists also caused a depression of the tetrodotoxin resistant action potential. Electroencephalographic power spectral analysis showed that adenosine perfusion into the basal forebrain increased the relative power in the delta frequency band, whereas higher frequency bands theta, alpha, beta and gamma showed a decrease. This trailblazing study was conducted on active and alert mice by researchers at New York University's Langone Medical Center and its Neuroscience Institute.
. These areas overlap, in part, with those where chemical, thermal and electrical stimulations evoke sleep, and where lesions suppress sleep. The arborization pattern and postsynaptic targets of corticofugal axons in basal forebrain areas have been studied by the combination of anatomical tract-tracing and pre- and postembedding immunocytochemistry. These inputs facilitate thalamocortical transmission. The full characterization of the genes encoding orexin and its two cognate receptors enabled the rapid development of in vitro and ex vivo assays with which to identify lead compound structures and to optimize potency and pharmacokinetic properties.
Conversely, cessation of histaminergic activity may play a role in initiation and maintenance of sleep. Systemic administration of p-chlorophenylalanine, a potent serotonin synthesis inhibitor produces long lasting insomnia. Cataplexy is often triggered by strong, generally positive emotion while consciousness is preserved during the attack. Orexinergic neurons are most active during wakefulness and fall silent during inactive periods, a prolonged disruption in signaling most profoundly resulting in hypersomnia and narcolepsy. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. Orexin neurons are thought to function as the sensor of energy balance. Sleep-waking discharge of neurons in the posterior lateral hypothalamus of the albino rat.
A schematic diagram to illustrate the integrative physiological roles of orexin neurons. The sleep switch: hypothalamic control of sleep and wakefulness. Electrophysiological studies revealed that increasing extracellular glucose concentrations induce striking hyperpolarizations, while decreasing the glucose concentration induces depolarization and increases the frequency of action potentials of orexin neurons ;. However, there are many controversial findings. Recent studies indicate that the arousal deficits in narcolepsy are associated with the activation failure of the basal forebrain cholinergic systems resulting from orexinergic deficiencies Arrigoni et al.
Many of the disorders discussed have a developmental etiology and a postpubertal age of onset. The orexin neurones play an essential role in driving arousal and in maintaining normal wakefulness. Differential expression of orexin receptors 1 and 2 in the rat brain. A key switch in the hypothalamus shuts off this arousal system during sleep. A broad role for melanopsin in nonvisual photoreception.
Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state. It is the manifestation of increased activity in the cortex cortical activation or desynchronization. Other hypothalamic neurons stabilize the switch, and their absence results in inappropriate switching of behavioural states, such as occurs in narcolepsy. It was found that the dynamics of desensitization to dynorphin can mediate a clear shift from a network in which firing is suppressed by dynorphin-mediated inhibition to a network of neurons with high firing rates sustained by orexin-mediated excitation. These findings suggest that these regions mediate the effects of orexins. They exhibited prominent hyperpolarization-activated inward currents and subthreshold 'spikelets', suggestive of electrical coupling. Intracerebroventricular injection of orexin induces water intake as well as food intake.
Regulation of Orexin Neurons by Humoral Factors Motivated behaviors such as food-seeking are deeply involved in maintenance of arousal. Activity of serotonin-containing neurons in nucleus raphe magnus in freely moving cats. This article describes the characteristics of mechanisms mediating sleep and arousal, their neurological substrates, and the cellular, neurochemical, and network properties of those substrates. The histamine levels in the brain fluctuate according to circadian rhythm and correlate with neuronal activity in histamine neurons during waking. DeMartinis, Andrew Winokur, in , 2012 Basic and Clinical Pharmacology Histamine is a neurotransmitter known to promote wakefulness and vigilance.
Since orexin neurons signal arousal need, and excite other wake-promoting neurons, their actions illuminate nonredundant principles of arousal control. Indeed, the frequency of cataplexy is not high in these mice. In the medial septum, the diagonal band and the nucleus basalis only cholinergic neurons were marked by Cy3-192IgG. Brain Mechanisms of Sleep eds McGinty, D. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity.