Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats

Greco, Mary Ann; Shiromani, Priyattam J.

doi:10.1016/s0169-328x(01)00039-0

Cited by 142 publications

(88 citation statements)

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“…First, orexin neurons project to the brain stem mesencephalic trigeminal nucleus (MTN) and the trigeminal motor nucleus (TMN) (Date et al 1999;Nambu et al 1999). Both orexin receptor-1 and -2 were shown to be expressed at the protein and mRNA levels in the MTN as well as TMN of the rat with the use of in situ hybridization and immunohistochemical methods (Greco and Shiromani 2001). MTN neurons receive orexin-A hypothalamic innervation with a somatotopic arrangement of the projections in the nucleus (Stoyanova and Lazarov 2005), and orexin-B immunoreactive fibers and terminals innervate the sensory and motor neurons controlling masticatory muscles (Zhang et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Analyses of the facilitatory effect of orexin on eating and masticatory muscle activity in rats

Tsuji

Yamamoto

Tanaka

et al. 2011

Journal of Neurophysiology

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Analyses of the facilitatory effect of orexin on eating and masticatory muscle activity in rats. J Neurophysiol 106: 3129 -3135, 2011. First published September 21, 2011 doi:10.1152/jn.01108.2010.-The orexins (orexin-A and orexin-B) are neuropeptides that are secreted from neurons in the lateral hypothalamus and that participate in the regulation of feeding behavior. It remains to be determined, however, how the orexins exert their effects on feeding behavior, including masticatory movements. To this end, we analyzed food intake behavior and masticatory muscle activity using video analysis and electromyography (EMG) recording methods. The results showed that the cumulative food intake over 4 h was larger in rats intraventricularly injected with either orexin-A or orexin-B than in saline-injected control rats. The latency to eating and the feeding time for a fixed amount of pellets were shortened by injections of orexins in a dose-dependent manner, with a more potent effect by orexin-A than orexin-B. The shorter feeding time corresponded to a decreased number of chewing cycles. EMG recordings from both the digastric and masseter muscles showed two distinct patterns of bursts corresponding to the gnawing and chewing phases. After the injection of orexin-A, the magnitude of the bursts became larger in both phases in the masseter muscle, the burst duration became longer in the chewing phase in the masseter muscle, and the interburst interval became shortened in the gnawing phase in both muscles. Consequently, the burst frequency in the chewing phase was increased in the digastric muscle and, conversely, reduced in the masseter muscle. These results suggest that the orexin-A-induced facilitatory feeding behavior is characterized by a dynamic jaw-opener activity that opens the mouth rapidly and a powerful jaw-closer activity for crushing the increased amount of food taken into the mouth. The possible involvement of orexin-A in binge eating disorder is discussed. orexigenic neuropeptide; feeding behavior; mastication; electromyogram FEEDING IS AN INDISPENSABLE life activity to take in essential nutrients and maintain energy homeostasis. This behavior is known to be regulated by the reciprocal activation of the feeding and satiety centers in the lateral hypothalamic area and ventromedial nucleus of the hypothalamus, respectively (Morgane 1961). Feeding behavior is also controlled by chemical mediators such as blood-borne glucose (Le Magnen 1984) and free fatty acids (Oomura et al. 1975), as well as leptin, which is produced by white adipose tissue (Zhang et al. 1994), and neuropeptide Y (NPY), ␣-melanin-concentrating hormone (␣-MCH), agouti-related peptide (AgRP), dynorphin, and the orexins (orexin-A and orexin-B), which are produced in the hypothalmic nuclei, all of which are known to be orexigenic neuropeptides (Clark et al. 1984;Ollmann et al. 1997;Qu et al. 1996;Sainsbury et al. 2007;Sakurai et al. 1998). Among the orexigenic neuropeptides, ␣-MCH and the orexins are unique in the sense that they are produced by the...

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Section: Discussionmentioning

confidence: 99%

Analyses of the facilitatory effect of orexin on eating and masticatory muscle activity in rats

Tsuji

Yamamoto

Tanaka

et al. 2011

Journal of Neurophysiology

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“…Moderate to dense orexin projections to the locus coeruleus and neighbouring SubC region have been demonstrated (Peyron et al, 1998) and orexin receptors are present within the SubC (Greco and Shiromani, 2001). Thus, this is a likely region where orexins act to regulate muscle tone.…”

Section: Abbreviationsmentioning

confidence: 95%

Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins

et al. 2006

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Pharmacological, lesion and single-unit recording techniques in several animal species have identified a region of the pontine reticular formation (Subcoeruleus, SubC) just ventral to the locus coeruleus as critically involved in the generation of rapid-eye-movement (REM) sleep. However, the intrinsic membrane properties and responses of SubC neurons to neurotransmitters important in REM sleep control, such as acetylcholine and orexins/hypocretins, have not previously been examined in any animal species and thus were targeted in this study.We obtained whole-cell patch-clamp recordings from visually identified SubC neurons in rat brain slices in vitro. Two groups of large neurons (mean diameter 30 and 27μm) were tentatively identified as cholinergic (rostral SubC) and noradrenergic (caudal SubC) neurons. SubC reticular neurons (noncholinergic, non-noradrenergic) showed a medium-sized depolarizing sag during hyperpolarizing current pulses and often had a rebound depolarization (low-threshold spike, LTS). During depolarizing current pulses they exhibited little adaptation and fired maximally at 30-90 Hz. Those SubC reticular neurons excited by carbachol (n=27) fired spontaneously at 6 Hz, often exhibited a moderately sized LTS, and varied widely in size (17-42 μm). Carbachol-inhibited SubC reticular neurons were medium-sized (15-25 μm) and constituted two groups. The larger group (n=22) was silent at rest and possessed a prominent LTS and associated 1-4 action potentials. The second, smaller group (n=8) had a delayed return to baseline at the offset of hyperpolarizing pulses. Orexins excited both carbachol excited and carbachol inhibited SubC reticular neurons.SubC reticular neurons had intrinsic membrane properties and responses to carbachol similar to those described for other reticular neurons but a larger number of carbachol inhibited neurons were found (> 50 %), the majority of which demonstrated a prominent LTS and may correspond to PGO-on neurons. Some or all carbachol-excited neurons are presumably REM-on neurons.Keywords rapid-eye-movement; whole-cell; in vitro; sublaterodorsal; hypocretin; narcolepsy NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptAbbreviations ACSF Artificial cerebrospinal fluid; AHP Afterhyperpolarization; AP Action potential; CARB Carbachol; CARB-E Carbachol excited; CARB-I Carbachol inhibited; CCD Charge coupled device; ChAT Choline acetyltransferase; DAB Diaminobenzidine; DC Direct current; GABA Gammaamino-butyric acid; GAD67 glutamic acid decarboxylase 67 kDa isoform; HCN Hyperpolarization activated and cyclic nucleotide gated cation channels; IACUC Institutional Animal Care and Use committee; IR-DIC Infra-red differential interference contrast; LC locus coeruleus; LDT laterodorsal tegmental nucleus; LTS low-threshold spike; mPRF medial pontine reticular formation; nNOS neuronal nitric oxide synthase; Ox A Orexin A; PGO pontine-geniculate-occipital waves; PnC pontine nucleus caudalis; PnO pontine nucleus oralis; P waves Pontine component of PGO wave...

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“…These three neuronal populations have been implicated in arousal based on pharmacological studies (Jones, 2005) and on the firing patterns of their respective neurons (Chu and Bloom, 1973;John et al, 2004;Lee et al, 2005). HCRT receptors are present on their neurons (Greco and Shiromani, 2001;Marcus et al, 2001), and application of HCRT in the BF (Blanco-Centurion et al, 2006b), TMN (Huang et al, 2001), or LC (Bourgin et al, 2000) has a potent arousing effect. Individual lesions of the BF cholinergic neurons (BlancoCenturion et al, 2006a), TMN , or LC does not change daily amounts of sleep-wake, but this might be because the other nonlesioned arousal groups compensate and stabilize the sleep-wake network.…”

Section: Introductionmentioning

confidence: 99%

Effects of Saporin-Induced Lesions of Three Arousal Populations on Daily Levels of Sleep and Wake

Blanco-Centurión¹,

Gerashchenko²,

Shiromani³

2007

J. Neurosci.

150

112

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The hypocretin (HCRT) neurons are located only in the perifornical area of the lateral hypothalamus and heavily innervate the cholinergic neurons in the basal forebrain (BF), histamine neurons in the tuberomammillary nucleus (TMN), and the noradrenergic locus ceruleus (LC) neurons, three neuronal populations that have traditionally been implicated in regulating arousal. Based on the innervation, HCRT neurons may regulate arousal by driving these downstream arousal neurons. Here, we directly test this hypothesis by a simultaneous triple lesion of these neurons using three saporin-conjugated neurotoxins. Three weeks after lesion, the daily levels of wake were not changed in rats with double or triple lesions, although rats with triple lesions were asleep more during the light-to-dark transition period. The double-and triple-lesioned rats also had more stable sleep architecture compared with nonlesioned saline rats. These results suggest that the cholinergic BF, TMN, and LC neurons jointly modulate arousal at a specific circadian time, but they are not essential links in the circuitry responsible for daily levels of wake, as traditionally hypothesized.

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Hypocretin receptor protein and mRNA expression in the dorsolateral pons of rats

Cited by 142 publications

References 13 publications

Analyses of the facilitatory effect of orexin on eating and masticatory muscle activity in rats

Analyses of the facilitatory effect of orexin on eating and masticatory muscle activity in rats

Electrophysiological characterization of neurons in the dorsolateral pontine rapid-eye-movement sleep induction zone of the rat: Intrinsic membrane properties and responses to carbachol and orexins

Effects of Saporin-Induced Lesions of Three Arousal Populations on Daily Levels of Sleep and Wake

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