Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Jl, Guan; Uehara, Kichio; Lu, Shan; Qp, Wang; Funahashi, Hiroomi; Sakurai, Takeshi; Yanagizawa, M; Shioda, Seiji

doi:10.1038/sj.ijo.0802155

Cited by 116 publications

(79 citation statements)

References 46 publications

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“…Renewed interest in the hypothalamus has emerged due to the discovery of the hypocretinergic system which has been suggested to be involved in the control of motor activity, sleep and wakefulness (reviewed by (Siegel, 2004, Sutcliffe and de Lecea, 2002, Taheri, et al, 2002). MCHergic neurons are intermingled with the hypocretinergic neurons in the hypothalamus and their projections are strikingly similar (Bayer, et al, 2002, Bittencourt, et al, 1992, Guan, et al, 2002, Peyron, et al, 1998, Skofitsch, et al, 1985; this anatomical data suggest that the MCHergic neurons may also contribute to the regulation of motor activity, sleep and waking functions. However, very few reports examined the role of MCH in relation to these functions.…”

Section: Discussionmentioning

confidence: 70%

“…MCHergic fibers were in close relationship with the hypocretinergic neurons, and vice versa, suggesting synaptic contacts between them; however, confocal and electron microscopic studies will be necessary to confirm synaptic contacts between these cells. Such reciprocal synaptic contacts have been demonstrated in rats (Guan, et al, 2002). This anatomical relationship as well as the presence of hypocretinergic receptors on MCHergic neurons suggests an important functional interaction between these systems (Backberg, et al, 2002).…”

Section: Discussionmentioning

confidence: 79%

“…Based upon experiments utilizing Fos immunoreactivity as a marker of neuronal activity as well as MCH intraventricular microinjections, Verret et al suggested that MCH is a powerful hypnogenic factor that plays a crucial role in the control of active (REM) sleep (AS) in the rat (Verret, et al, 2003). In hamsters and rats, MCHergic neurons are intermingled with hypocretinergic neurons and make numerous synaptic contacts with these cells (Bayer, et al, 2002, Guan, et al, 2002, Khorooshi and Klingenspor, 2005. The hypocretinergic system has an anatomical organization similar to the MCHergic system (Peyron, et al, 1998), and it has been proposed to be involved in the regulation of behavioral states; deficits in this system have been associated with narcolepsy/cataplexy (Siegel, 2004, Sutcliffe and de Lecea, 2002, Taheri, et al, 2002.…”

Section: Introductionmentioning

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: 70%

Section: Discussionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…To rule out the possibility of nonspecific cell loss in other lateral hypothalamic cell populations, we also examined the level of orexin, a marker for another neuronal cell type in the lateral hypothalamus and GFAP, a glial marker. MCH and orexin are expressed in distinct neuronal populations in the lateral hypothalamus, and both have been implicated in the regulation of feeding behavior (Guan et al, 2002). We used orexin antibodies to immunostain the brain sections of 8-and 15-week-old MCH/ataxin-3 mice and their wild-type littermates.…”

Section: Normal Expression Of Orexin and Gfap In Mch/ataxin-3 Transgementioning

confidence: 99%

“…MCH is predominantly expressed in the lateral hypothalamic area, a region implicated in feeding behavior (Guan et al, 2002). MCH neurons make monosynaptic projections throughout the brain to a wide variety of structures that are known to participate in feeding (Zamir et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Late-Onset Leanness in Mice with Targeted Ablation of Melanin Concentrating Hormone Neurons

Alon¹,

Friedman²

2006

J. Neurosci.

107

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The observation that loss of orexin (hypocretin) neurons causes human narcolepsy raises the possibility that other acquired disorders might also result from loss of hypothalamic neurons. To test this possibility for body weight, mice with selective loss of melanin concentrating hormone (MCH) neurons were generated. MCH was chosen to test because induced mutations of the MCH gene in mice cause hypophagia and leanness. Mice with ablation of MCH neurons were generated using toxin (ataxin-3)-mediated ablation strategy. The mice appeared normal but, after 7 weeks, developed reduced body weight, body length, fat mass, lean mass, and leptin levels. Leanness was characterized by hypophagia and increased energy expenditure. To study the role of MCH neurons on obesity secondary to leptin deficiency, we generated mice deficient in both ob gene product (leptin) and MCH neurons. Absence of MCH neurons in ob/ob mice improved obesity, diabetes, and hepatic steatosis, suggesting that MCH neurons are important mediators of the response to leptin deficiency. These data show that loss of MCH neurons can lead to an acquired leanness. This has implications for the pathogenesis of acquired changes of body weight and might be considered in clinical settings characterized by substantial weight changes later in life.

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Hypocretin/Orexin System

Sutcliffe

Lecea

2007

Handbook of Contemporary Neuropharmacology

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The hypocretins (also called the orexins) are excitatory neurotransmitters produced in a few thousand neurons of the lateral hypothalamus. Two G protein‐coupled receptors for the hypocretins have different distributions within the CNS and differential affinities for the two hypocretin peptides. Hypocretins efferents project to areas within the posterior hypothalamus that are implicated in feeding behaviors and hormone secretion. Hypocretin fibers also project to diverse targets in other brain regions and the spinal cord, including several areas implicated in cardiovascular function and sleep‐wake regulation. Administration of the hypocretins stimulates food intake, affects blood pressure, hormone secretion and locomotor activity, and increases wakefulness while suppressing rapid eye movement (REM) sleep. Narcolepsy is a disorder of the hypocretin system. One aspect of hypocretin activity is the direct excitation of cholinergic forebrain neurons, brainstem monoaminergic REM‐off neurons in the locus coeruleus and dorsal raphe nucleus, and histaminergic tuberomammillary nucleus, which together suppress slow‐wave sleep. The hypocretins also modulate the activity of cholinergic REM‐on neurons in the brainstem, which gate REM entry.

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Reciprocal synaptic relationships between orexin- and melanin-concentrating hormone-containing neurons in the rat lateral hypothalamus: a novel circuit implicated in feeding regulation

Cited by 116 publications

References 46 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

Late-Onset Leanness in Mice with Targeted Ablation of Melanin Concentrating Hormone Neurons

Hypocretin/Orexin System

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