Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clockCitation formats

  • External authors:
  • Mino D C Belle
  • Alun Hughes
  • Massimo Pierucci
  • Denis Burdakov

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Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock. / Belle, Mino D C; Hughes, Alun; Bechtold, David A.; Cunningham, Peter; Pierucci, Massimo; Burdakov, Denis; Piggins, Hugh D.

In: Journal of Neuroscience, Vol. 34, No. 10, 2014, p. 3607-3621.

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Belle, Mino D C ; Hughes, Alun ; Bechtold, David A. ; Cunningham, Peter ; Pierucci, Massimo ; Burdakov, Denis ; Piggins, Hugh D. / Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 10. pp. 3607-3621.

Bibtex

@article{c719f5ff6ef34c1ba1253560c68fc044,
title = "Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock",
abstract = "Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K+ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain. {\circledC} 2014 Belle et al.",
keywords = "Arousal, Circadian, Electrophysiology, GABA, Orexin A, Suprachiasmatic",
author = "Belle, {Mino D C} and Alun Hughes and Bechtold, {David A.} and Peter Cunningham and Massimo Pierucci and Denis Burdakov and Piggins, {Hugh D.}",
note = "We thank the BBSRC and the Wellcome Trust for project grant funding to H.D.P. and D.B. We thank Rayna Samuels for technical assistance and Dr. Benjamin Boutrel for prepro-orexin knock-out mouse brains.",
year = "2014",
doi = "10.1523/JNEUROSCI.3388-13.2014",
language = "English",
volume = "34",
pages = "3607--3621",
journal = "The Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "10",

}

RIS

TY - JOUR

T1 - Acute suppressive and long-term phase modulation actions of orexin on the mammalian circadian clock

AU - Belle, Mino D C

AU - Hughes, Alun

AU - Bechtold, David A.

AU - Cunningham, Peter

AU - Pierucci, Massimo

AU - Burdakov, Denis

AU - Piggins, Hugh D.

N1 - We thank the BBSRC and the Wellcome Trust for project grant funding to H.D.P. and D.B. We thank Rayna Samuels for technical assistance and Dr. Benjamin Boutrel for prepro-orexin knock-out mouse brains.

PY - 2014

Y1 - 2014

N2 - Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K+ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain. © 2014 Belle et al.

AB - Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K+ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain. © 2014 Belle et al.

KW - Arousal

KW - Circadian

KW - Electrophysiology

KW - GABA

KW - Orexin A

KW - Suprachiasmatic

U2 - 10.1523/JNEUROSCI.3388-13.2014

DO - 10.1523/JNEUROSCI.3388-13.2014

M3 - Article

VL - 34

SP - 3607

EP - 3621

JO - The Journal of Neuroscience

JF - The Journal of Neuroscience

SN - 0270-6474

IS - 10

ER -