Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle

Lee, Maan‐Gee; Hassani, Oum Kaltoum; Jones, Barbara E.

doi:10.1523/jneurosci.1887-05.2005

Cited by 783 publications

(647 citation statements)

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“…In addition, unit recordings have revealed non-hypocretinergic neurons that increase their firing rate in conjunction with motor activity (Lee, et al, 2005). Although hypocretinergic neurons seem to be primarily involved in somatomotor activity (Kiyashchenko, et al, 2002, Lee, et al, 2005, Martins, et al, 2004, Mileykovskiy, et al, 2005, Torterolo, et al, 2001, our results suggest that additional, as-yetunidentified neurons in this region may also be involved in this function. The activity of these unidentified neurons decreased during QS, which is in agreement with electrophysiological studies (Alam, et al, 2002).…”

Section: Discussionmentioning

confidence: 49%

“…In this regard, electrolytic and chemical lesions in this region, as well the injection of GABA agonists, produce a decrease in locomotion while electrical and chemical stimulation increases locomotor activity (Blake and Gladfelter, 1986, Gladfelter and Brobeck, 1962, Levy and Sinnamon, 1990, Marciello and Sinnamon, 1990, Shekhar and DiMicco, 1987, Sinnamon, 1984, Sinnamon, 1990, Sinnamon and Sklow, 1990, Sinnamon and Stopford, 1987, Wardas, et al, 1988. In addition, unit recordings have revealed non-hypocretinergic neurons that increase their firing rate in conjunction with motor activity (Lee, et al, 2005). Although hypocretinergic neurons seem to be primarily involved in somatomotor activity (Kiyashchenko, et al, 2002, Lee, et al, 2005, Martins, et al, 2004, Mileykovskiy, et al, 2005, Torterolo, et al, 2001, our results suggest that additional, as-yetunidentified neurons in this region may also be involved in this function.…”

Section: Discussionmentioning

confidence: 99%

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MCH-containing neurons in the hypothalamus of the cat: Searching for a role in the control of sleep and wakefulness

Torterolo

Sampogna²,

Morales

et al. 2006

Brain Research

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Neurons that utilize melanin-concentrating hormone (MCH) and others that employ hypocretin as neurotransmitter are located in the hypothalamus and project diffusely throughout the CNS, including areas that participate in the generation and maintenance of the states of sleep and wakefulness. In the present report, immunohistochemical methods were employed to examine the distribution of MCHergic and hypocretinergic neurons. In order to test the hypothesis that the MCHergic system is capable of influencing specific behavioral states, we studied Fos immunoreactivity in MCHcontaining neurons during 1) quiet wakefulness, 2) active wakefulness with motor activity, 3) active wakefulness without motor activity, 4) quiet sleep, and, 5) active sleep induced by carbachol (AScarbachol). We determined that MCHergic neuronal somata in the cat are intermingled with hypocretinergic neurons in the dorsal and lateral hypothalamus, principally in the tuberal and tuberomammillary regions; however, hypocretinergic neurons extended more in the anteriorposterior axis than MCHergic neurons. Axosomatic and axodendritic contacts were common between these neurons. In contrast to hypocretinergic neurons, which are known to be active during motor activity and AS-carbachol, Fos immunoreactivity was not observed in MCH-containing neurons in conjunction with any of the preceding behavioral conditions. Non-MCHergic, non-hypocretinergic neurons that expressed c-fos during active wakefulness with motor activity were intermingled with MCH and hypocretin-containing neurons, suggesting that these neurons are related to some aspect of motor function. Further studies are required to elucidate the functional sequela of the interactions between MCHergic and hypocretinergic neurons and the phenotype of the other neurons that were active during motor activity.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

MCH-containing neurons in the hypothalamus of the cat: Searching for a role in the control of sleep and wakefulness

Torterolo

Sampogna²,

Morales

et al. 2006

Brain Research

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“…Orexin neurons are known to discharge during active waking [41], and the excitability is inhibited by glucose [1,4,6]. In addition, changes in blood glucose levels negatively correlate with expression of the gene encoding prepro-orexin in the mouse hypothalamus [11].…”

Section: Discussionmentioning

confidence: 99%

Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice

et al. 2008

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Aims/hypothesis Orexin/hypocretin is a hypothalamic neuropeptide that regulates motivated behaviours, such as feeding and arousal, and, importantly, is also involved in energy homeostasis. The aim of this study was to reveal the role of orexin in the regulation of insulin sensitivity for glucose metabolism. Methods Orexin knockout mice fasted overnight underwent oral glucose tolerance testing and insulin tolerance testing. The impact of orexin deficiency on insulin signalling was studied by Western blotting to measure levels of Akt phosphorylation and its upstream and downstream molecules in the hypothalamus, muscle and liver in orexin knockout mice. Results We found that orexin deficiency caused the agerelated development of impaired glucose tolerance and insulin resistance in both male mice without obesity and female mice with mild obesity, fed a normal chow diet. When maintained on a high-fat diet, these abnormalities became more pronounced exclusively in female orexin knockout mice that developed severe obesity. Insulin signalling through Akt was disrupted in peripheral tissues of middle-aged (9-month-old) but not young adult (2-to-3-month-old) orexin knockout mice fed a normal chow diet. Moreover, basal levels of hypothalamic Akt phosphorylation were abnormally elevated in orexin knockout mice at every age studied, and insulin stimulation failed to increase the level of phosphorylation. Similar abnormalities were observed with respect to GSK3β phosphorylation in the hypothalamus and peripheral tissues of middle-aged orexin knockout mice. Conclusions/interpretation Our results demonstrate a novel role for orexin in hypothalamic insulin signalling, which is likely to be responsible for preventing the development of peripheral insulin resistance with age.

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“…Largely speaking, the monoamines are most active during wakefulness, decrease during NREM sleep and are mostly absent during REM sleep (Aston--Jones and Bloom 1981;Saper et al 2010). Orexin neurons, however, are mostly active during wakefulness and silent during both NREM and REM sleep (Mileykovskiy et al 2005;Lee et al 2005). Additionally, orexin has been proposed to be responsible for the stability of the sleep--wake switch, controlling the transition from wake to sleep in a timely manner, preventing unexpected and sudden lapses into sleep, such as those typical of the sleep disorder narcolepsy (a sleep disorder characterised by frequent, unintentional lapses into sleep) (Saper et al 2001).…”

mentioning

confidence: 99%

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

Barclay

Gregory

2013

The Neurobiology of Childhood

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Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities.Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co--occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia, and emotional/ behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

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Discharge of Identified Orexin/Hypocretin Neurons across the Sleep-Waking Cycle

Cited by 783 publications

References 39 publications

MCH-containing neurons in the hypothalamus of the cat: Searching for a role in the control of sleep and wakefulness

MCH-containing neurons in the hypothalamus of the cat: Searching for a role in the control of sleep and wakefulness

Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice

Sleep in Childhood and Adolescence: Age-Specific Sleep Characteristics, Common Sleep Disturbances and Associated Difficulties

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