Orexin Neurons Function in an Efferent Pathway of a Food-Entrainable Circadian Oscillator in Eliciting Food-Anticipatory Activity and Wakefulness

Mieda, Michihiro; Williams, Suzanne; Sinton, Christopher M.; Richardson, James A.; Sakurai, Takeshi; Yanagisawa, Masashi

doi:10.1523/jneurosci.3171-04.2004

Cited by 191 publications

(146 citation statements)

References 42 publications

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“…We found that calorie restriction caused an increase in locomotor activity just before the dark phase (supplemental Fig. C, available at www.jneurosci.org as supplemental material), which is similar to the food-anticipatory activity published previously (Mieda et al, 2004). As reported, this food-anticipatory activity was blunted in orexin knock-out mice.…”

Section: Resultssupporting

confidence: 89%

“…The hypothalamic neuropeptide orexin (hypocretin) offers an attractive candidate for understanding the behavioral effects of calorie restriction. The activity of orexin neurons is regulated by energy balance (Yamanaka et al, 2003), and orexin neurons mediate certain complex behaviors such as the increase in locomotor activity observed during periods of reduced calorie availability and after withdrawal from morphine (Georgescu et al, 2003;Yamanaka et al, 2003;Mieda et al, 2004). Furthermore, orexin signaling has been implicated in the regulation of food and drug reward, indicating a role for orexin signaling in emotional processes (Harris et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction

Lutter

Krishnan²,

Russo³

et al. 2008

J. Neurosci.

214

160

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During periods of reduced food availability, animals must respond with behavioral adaptations that promote survival. Despite the fact that many psychiatric syndromes include disordered eating patterns as a component of the illness, little is known about the neurobiology underlying behavioral changes induced by short-term calorie restriction. Presently, we demonstrate that 10 d of calorie restriction, corresponding to a 20 -25% weight loss, causes a marked antidepressant-like response in two rodent models of depression and that this response is dependent on the hypothalamic neuropeptide orexin (hypocretin). Wild-type mice, but not mice lacking orexin, show longer latency to immobility and less total immobility in the forced swim test after calorie restriction. In the social defeat model of chronic stress, calorie restriction reverses the behavioral deficits seen in wild-type mice but not in orexin knock-out mice. Additionally, chronic social defeat stress induces a prolonged reduction in the expression of prepro-orexin mRNA via epigenetic modification of the orexin gene promoter, whereas calorie restriction enhances the activation of orexin cells after social defeat. Together, these data indicate that orexin plays an essential role in mediating reduced depression-like symptoms induced by calorie restriction.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction

Lutter

Krishnan²,

Russo³

et al. 2008

J. Neurosci.

214

160

View full text Add to dashboard Cite

show abstract

“…They also stimulate appetite and control brain reward systems (Sakurai et al, 1998;Harris et al, 2005;Borgland et al, 2006). In mice, loss of orexins prevents fasting-induced wakefulness and locomotor activity (Yamanaka et al, 2003;Mieda et al, 2004) and can cause abnormalities in body-weight regulation (Hara et al, 2001). The activity of orexin cells is highest during active wakefulness and lowest during slow-wave sleep (Lee et al, 2005;Mileykovskiy et al, 2005) and is regulated by numerous central inputs (Sakurai et al, 2005), as well as by circulating signals of body energy status, such as leptin and glucose (Yamanaka et al, 2003;Burdakov et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

Zubcevic²,

Ashcroft³

et al. 2007

J. Neurosci.

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Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus (ARC) suppress appetite, and lack of POMC-derived peptides or electrical silencing of POMC neurons causes obesity. ARC POMC neurons are surrounded by nerve terminals containing the wakefulness-promoting peptides orexins/hypocretins, but whether orexin affects their electrical activity has not been tested directly. Here we identify living ARC POMC cells in mouse brain slices by targeted expression of green fluorescent protein. Using whole-cell patch-clamp recordings, we show that orexin suppresses the spontaneous action potential firing of these neurons. Orexin-induced inhibition involves membrane hyperpolarization, a decreased excitatory synaptic drive, and an increased frequency of GABAergic inputs. Our results suggest a reduction in the electrical activity of ARC POMC neurons, which is mediated by changes in presynaptic inputs, contributes to the appetite-enhancing action of orexins.

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“…These results were confirmed by another group that studied the involvement of orexin in the establishment and maintenance of FAA induced by restricted feeding (Mieda et al, 2004). Interestingly, activity of orexinergic neurons markedly increases during food anticipation under restricted feeding in wild-type mice (Mieda et al, 2004). Taken together, these studies would suggest that orexin neurons may convey an efferent signal from the FEC, thus increasing wakefulness, and promoting and maintaining FAA in the hours prior to food.…”

Section: The Orexinergic Pathway An Efferent Of the Fec Promoting Faamentioning

confidence: 54%

“…It seems that orexinergic neurons would not generate FAA per se, but they would participate in the wakefulness component of FAA (Akiyama et al, 2004). These results were confirmed by another group that studied the involvement of orexin in the establishment and maintenance of FAA induced by restricted feeding (Mieda et al, 2004). Interestingly, activity of orexinergic neurons markedly increases during food anticipation under restricted feeding in wild-type mice (Mieda et al, 2004).…”

Section: The Orexinergic Pathway An Efferent Of the Fec Promoting Faamentioning

confidence: 76%

“Feeding time” for the brain: A matter of clocks

Feillet

Albrecht

Challet

2006

Journal of Physiology-Paris

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Circadian clocks are autonomous time-keeping mechanisms that allow living organisms to predict and adapt to environmental rhythms of light, temperature and food availability. At the molecular level, circadian clocks use clock and clock-controlled genes to generate rhythmicity and distribute temporal signals. In mammals, synchronization of the master circadian clock located in the suprachiasmatic nuclei of the hypothalamus is accomplished mainly by light stimuli. Meal time, that can be experimentally modulated by temporal restricted feeding, is a potent synchronizer for peripheral oscillators with no clear synchronizing influence on the suprachiasmatic clock. Furthermore, food-restricted animals are able to predict meal time, as revealed by anticipatory bouts of locomotor activity, body temperature and plasma corticosterone. These food anticipatory rhythms have long been thought to be under the control of a food-entrainable clock (FEC). Analysis of clock mutant mice has highlighted the relevance of some, but not all of the clock genes for foodentrainable clockwork. Mutations of Clock or Per1 do not impair expression of food anticipatory components, suggesting that these clock genes are not essential for food-entrainable oscillations. By contrast, mice mutant for Npas2 or deficient for Cry1 and Cry2 show more or less altered responses to restricted feeding conditions. Moreover, a lack of food anticipation is specifically associated with a mutation of Per2, demonstrating the critical involvement of this gene in the anticipation of meal time. The actual location of the FEC is not yet clearly defined. Nevertheless, current knowledge of the putative brain regions involved in food-entrainable oscillations is discussed. We also describe several neurochemical pathways, including orexinergic and noradrenergic, likely to participate in conveying inputs to and outputs from the FEC to control anticipatory processes.

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Orexin Neurons Function in an Efferent Pathway of a Food-Entrainable Circadian Oscillator in Eliciting Food-Anticipatory Activity and Wakefulness

Cited by 191 publications

References 42 publications

Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction

Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction

Electrical Inhibition of Identified Anorexigenic POMC Neurons by Orexin/Hypocretin

“Feeding time” for the brain: A matter of clocks

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