Functional Anatomy of the Sleep-Wakefulness Cycle: Wakefulness by Fernando Reinoso-Suárez Isabel de Andrés & Miguel Garzón

Author:Fernando Reinoso-Suárez, Isabel de Andrés & Miguel Garzón
Language: eng
Format: epub
Publisher: Springer Berlin Heidelberg, Berlin, Heidelberg

Lee et al. (2005a) recorded neurons in head-fixed rats over the SWC and labeled them with neurobiotin to identify them. They demonstrated that identified Hcrt/Orx neurons discharge during active W, decrease their discharge rate during quiet W and virtually cease firing during REM and NREM sleep. The neurons increase their firing before the end of REM sleep, heralding the return of waking and muscle tone by several seconds. Those authors conclude that the Hcrt/Orx neurons would stimulate arousal while antagonizing sleep and muscle atonia. Summing up, these and similar results from Mileykovskiy et al. (2005) are solid evidence that Hcrt/Orx neurons are active during W and silent during sleep. The Hcrt/Orx neuron discharge is positively correlated with EMG amplitude, and their increased firing prior to the return of muscle tone with awakening from REM sleep appears to stimulate awakening by recruiting other arousal systems (Jones 2008).

Hcrt/Orx neurons receive and are modulated by excitatory and inhibitory inputs. The excitatory susbstances are glutamate, ghrelin, cholecystokinin, neurotensin, vasopressin, oxytocin, glucagon-like peptide, corticotropin-releasing factor, mACh (affecting 27% of all Hcrt/Orx neurons), and ATP; the inhibitory susbstances are glucose, GABA, serotonin, noradrenaline, dopamine, neuropeptide Y, leptin, mACh (affecting 6% of Hcrt/Orx neurons), and adenosine (see Tsujino et al. 2005; Sakurai 2007). These impulses implicate the innervation of Hcrt/Orx neurons in a large number of brain structures that, in some cases, as Yamanaka et al. (2006) specify studying Hcrt/Orx neuron regulation by catecholamines, may be innervated directly or indirectly through other structures, most normally in a complex manner. Effectively, a feedback loop between Hcrt/Orx neurons and the LC and DR monoaminergic neurons might maintain the activity of the latter; decreases in monoaminergic neuron activity will decrease the inhibitory influence on Hcrt/Orx neurons, this disinhibition of Hcrt/Orx neurons would then increase the excitation of monoaminergic cells, thereby increasing W (Fig.3.5). It has not been easy to pinpoint the afferent connections of the Hcrt/Orx neurons because they are dispersed over a wide hypothalamic region. In addition, monoaminergic and peptidergic fibers may use “volume transmission,” which includes diffusion of signals through the extracellular and cerebrospinal fluid. Actually, tracing studies showed that projections of monoaminergic neurons to Hcrt/Orx neurons are sparse and that Hcrt/Orx neurons are apposed to NPY-containing peptidergic fibers. Also, extrasynaptic receptors can sense ambient ligands, which can act as neuromodulators (Sakurai 2007).

Recently, many of these afferents have been traced using a genetically encoded retrograde tracer or with a combination of anterograde and retrograde tracers (Sakurai et al. 2005; Yoshida et al. 2006). In summary, the Hcrt/Orx neurons receive abundant inputs from the lateral septum, preoptic area, including forebrain cholinergic neurons and GABAergic neurons of the peoptic area, and the posterior hypothalamus; consistent input from the the allocortex, claustrum, amygdala, basal bed nucleus of the stria terminalis and from many hypothalamic regions including the dorsomedial nucleus and lateral hypothalamus also reaches these neurons (Fig.3.8). The number of afferents from the brainstem is, in general, more moderate, the strongest coming from the periaqueductal gray matter, DR nucleus, and lateral parabrachial nucleus.

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