Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms

Chou, Tom; Scammell, Thomas E.; Gooley, Joshua J.; Gaus, Stephanie E.; Saper, Clifford B.; Lü, Jun

doi:10.1523/jneurosci.23-33-10691.2003

Cited by 481 publications

(403 citation statements)

References 55 publications

(81 reference statements)

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“…The SCN sends its densest projections to other hypothalamic nuclei, including the subparaventricular zone and dorsomedial hypothalamic nucleus, which are also required for normal circadian expression of behavioural rhythms, including feeding (17)(18)(19) . In addition to receiving input from appetite circuits, the dorsomedial hypothalamic nucleus contains different populations of neurons that project to the sleep-promoting ventrolateral preoptic nucleus and the wake-promoting lateral hypothalamic area (17) . The projection to the lateral hypothalamic area contacts neurons containing the neuropeptide orexin, which increases food-seeking behaviour and plays a key role in stabilising sleep-wake behaviour.…”

Section: Entrainment Of Feeding Circuits and Peripheral Clocksmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

135

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The circadian system temporally coordinates daily rhythms in feeding behaviour and energy metabolism. The objective of the present paper is to review the mechanisms that underlie circadian regulation of lipid metabolic pathways. Circadian rhythms in behaviour and physiology are generated by master clock neurons in the suprachiasmatic nucleus (SCN). The SCN and its efferent targets in the hypothalamus integrate light and feeding signals to entrain behavioural rhythms as well as clock cells located in peripheral tissues, including the liver, adipose tissue and muscle. Circadian rhythms in gene expression are regulated at the cellular level by a molecular clock comprising a core set of clock genes/proteins. In peripheral tissues, hundreds of genes involved in lipid biosynthesis and fatty acid oxidation are rhythmically activated and repressed by clock proteins, hence providing a direct mechanism for circadian regulation of lipids. Disruption of clock gene function results in abnormal metabolic phenotypes and impaired lipid absorption, demonstrating that the circadian system is essential for normal energy metabolism. The composition and timing of meals influence diurnal regulation of metabolic pathways, with food intake during the usual rest phase associated with dysregulation of lipid metabolism. Recent studies using metabolomics and lipidomics platforms have shown that hundreds of lipid species are circadian-regulated in human plasma, including but not limited to fatty acids, TAG, glycerophospholipids, sterol lipids and sphingolipids. In future work, these lipid profiling approaches can be used to understand better the interaction between diet, mealtimes and circadian rhythms on lipid metabolism and risk for obesity and metabolic diseases.

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Section: Entrainment Of Feeding Circuits and Peripheral Clocksmentioning

confidence: 99%

Circadian regulation of lipid metabolism

Gooley

2016

Proc. Nutr. Soc.

135

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“…For instance, to drive circadian rhythms in locomotor activity, the SCN sends direct projections and indirect projections with relay neurons in the subparaventircular nucleus (SPVN) to the dorsomedial hypothalamic nucleus (DMH), which conveys the SCN influences to locomotor activity through its output to lateral hypothalamic area (LHA) that contains orexin. Lesions of the DMH not only diminish the circadian rhythms of locomotor activity but also reduce the overall activity level (Chou et al, 2003). In addition, the DMH seems crucial for providing flexibility to adapt the behavioral and physiological cycles to 24-hour rhythm of food availability (Gooley et al, 2006) though it may not fully account for circadian rhythms in the food-anticipatory activity (Landry et al, 2006).…”

Section: Control Nodes Responsible For Scale Invariance Below 4 Hoursmentioning

confidence: 99%

The suprachiasmatic nucleus functions beyond circadian rhythm generation

et al. 2007

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We recently discovered that human activity possesses a complex temporal organization characterized by scale-invariant/self-similar fluctuations from seconds to ~4 hour-statistical properties of fluctuations remain the same at different time scales. Here, we show that scale-invariant activity patterns are essentially identical in humans and rats, and exist for up to ~24 hour: six-times longer than previously documented. Theoretically, such scale-invariant patterns can be produced by a neural network of interacting control nodes-system components with feedback loops-operating at different time scales. However such control nodes have not yet been identified in any neurophysiological model of scale invariance/self-similarity in mammals. Here we demonstrate that the endogenous circadian pacemaker (suprachiasmastic nucleus; SCN), known to modulate locomotor activity with a periodicity of ~24 hour, also acts as a major neural control node responsible for the generation of scale-invariant locomotor patterns over a broad range of time scales from minutes to at least 24 hour (rather than solely at ~24 hour). Remarkably, we found that SCN lesion in rats completely abolished the scale-invariant locomotor pattern between 4 and 24 hour and significantly altered the patterns at time scales <4 hour. Identification of the control nodes of a neural network responsible for scale invariance is the critical first step in understanding the neurophysiological origin of scale invariance/self-similarity. KeywordsActivity; Scale-invariance; Suprachiasmatic nucleus lesion; Human; Rat; Network The suprachiasmastic nucleus (SCN) in mammals generates self-sustained oscillations that orchestrate a wide range of neurophysiologic functions-from cellular processes to overt behaviors-with a time period of ~24 hour (Weaver, 1998). One of the fundamental processes influenced by the SCN is motor activity, which displays clear ~24 hour rhythms even under

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“…The PF region contains two neuronal groups, orexin (ORX) and melanin-concentrating hormone (MCH), involved in the control of sleep and wakefulness [27][28][29]. The DM region, comprising the hypothalamic dorsomedial and paraventricular nuclei, may also contribute to the circadian control of sleep [30], but is primarily involved in neuroendocrine and autonomic homeostasis, including the responses to stress [31]. In the PF region, GABA, MCH and ORX neurons have α 2 or α 3 subunits [24], ORX and MCH cells have subunits [21], and may also express β 2 and/or β 3 subunits [25].…”

Section: Effects Of Endogenous Gaba and Gaba A R Antagonist On Gaba Amentioning

confidence: 99%

Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro

Volgin

Kubin

2007

Biochemical and Biophysical Research Communications

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We tested whether GABA A receptor (R) subunit mRNA levels are homeostatically influenced by short-term exposure to GABA in two adjacent regions of the posterior hypothalamus. mRNA levels for seven GABA A R subunits and GABA-synthesizing enzyme (GAD) were quantified in the perifornical (PF) and dorsomedial (DM) hypothalamus following superfusion of slices for 90 min with a drug-free medium, GABA uptake blocker with or without GABA A R antagonist, gabazine, or GABA A R agonist with tetrodotoxin. Increasing endogenous GABA decreased mRNAs for all seven GABA A R subunits in the PF, and for three also in the DM, region; gabazine antagonized these effects in the PF region only and increased GAD-65 mRNA. Stimulation of GABA A Rs in the presence of tetrodotoxin decreased mRNA for one GABA A R subunit (β 1 ). We conclude that, in the PF region where GABA facilitates sleep, increased GABA release may limit GABA A R-mediated inhibition, whereas in the DM region, GABA-induced changes are mainly mediated by non-GABA A receptors.

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Critical Role of Dorsomedial Hypothalamic Nucleus in a Wide Range of Behavioral Circadian Rhythms

Cited by 481 publications

References 55 publications

Circadian regulation of lipid metabolism

Circadian regulation of lipid metabolism

The suprachiasmatic nucleus functions beyond circadian rhythm generation

Regionally selective effects of GABA on hypothalamic GABAA receptor mRNA in vitro

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