A neural circuit for circadian regulation of arousal - PubMed (original) (raw)

A neural circuit for circadian regulation of arousal

G Aston-Jones et al. Nat Neurosci. 2001 Jul.

Abstract

An unknown aspect of behavioral state regulation is how the circadian oscillator of the suprachiasmatic nucleus (SCN) regulates sleep and waking. In this report, we describe the necessary elements for a circuit that provides circadian regulation of arousal. Trans-synaptic retrograde tracing revealed a prominent indirect projection from the SCN to the noradrenergic nucleus locus coeruleus (LC), a brain arousal system. Double-labeling experiments revealed several possible links between the SCN and the LC, including the dorsomedial (DMH) and paraventricular hypothalamic nuclei (PVN), as well as medial and ventrolateral pre-optic areas. Lesion studies confirmed that the DMH is a substantial relay in this circuit. Next, neurophysiology experiments revealed circadian variations in LC impulse activity. Lesions of the DMH eliminated these circadian changes in LC activity, confirming the functionality of the SCN-DMH-LC circuit. These results reveal mechanisms for regulation of circadian and sleep-waking functions.

PubMed Disclaimer

Similar articles

• Knockdown of clock genes in the suprachiasmatic nucleus blocks prolactin surges and alters FRA expression in the locus coeruleus of female rats.
  Poletini MO, McKee DT, Kennett JE, Doster J, Freeman ME. Poletini MO, et al. Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1325-34. doi: 10.1152/ajpendo.00341.2007. Epub 2007 Aug 28. Am J Physiol Endocrinol Metab. 2007. PMID: 17726143
• Development of SCN connectivity and the circadian control of arousal: a diminishing role for humoral factors?
  Gall AJ, Todd WD, Blumberg MS. Gall AJ, et al. PLoS One. 2012;7(9):e45338. doi: 10.1371/journal.pone.0045338. Epub 2012 Sep 13. PLoS One. 2012. PMID: 23028945 Free PMC article.
• Suprachiasmatic nucleus in sleep-wake regulation.
  Moore RY. Moore RY. Sleep Med. 2007 Dec;8 Suppl 3:27-33. doi: 10.1016/j.sleep.2007.10.003. Sleep Med. 2007. PMID: 18032104 Review.
• Circadian regulation of sleep in mammals: role of the suprachiasmatic nucleus.
  Mistlberger RE. Mistlberger RE. Brain Res Brain Res Rev. 2005 Nov;49(3):429-54. doi: 10.1016/j.brainresrev.2005.01.005. Brain Res Brain Res Rev. 2005. PMID: 16269313 Review.

Cited by

• A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence.
  Gold MS, Blum K, Bowirrat A, Pinhasov A, Bagchi D, Dennen CA, Thanos PK, Hanna C, Lewandrowski KU, Sharafshah A, Elman I, Badgaiyan RD. Gold MS, et al. INNOSC Theranostics Pharmacol Sci. 2024;7(3):1918. doi: 10.36922/itps.1918. Epub 2024 Jul 29. INNOSC Theranostics Pharmacol Sci. 2024. PMID: 39119149 Free PMC article.
• The 5-min pupillary alertness test is sensitive to modafinil: a placebo controlled study in patients with sleep apnea.
  Nikolaou A, Schiza SE, Giakoumaki SG, Roussos P, Siafakas N, Bitsios P. Nikolaou A, et al. Psychopharmacology (Berl). 2008 Feb;196(2):167-75. doi: 10.1007/s00213-007-0949-y. Epub 2007 Sep 25. Psychopharmacology (Berl). 2008. PMID: 17899016 Clinical Trial.
• Entrainment of Circadian Rhythms Depends on Firing Rates and Neuropeptide Release of VIP SCN Neurons.
  Mazuski C, Abel JH, Chen SP, Hermanstyne TO, Jones JR, Simon T, Doyle FJ 3rd, Herzog ED. Mazuski C, et al. Neuron. 2018 Aug 8;99(3):555-563.e5. doi: 10.1016/j.neuron.2018.06.029. Epub 2018 Jul 12. Neuron. 2018. PMID: 30017392 Free PMC article.
• Orexin neurons are necessary for the circadian control of REM sleep.
  Kantor S, Mochizuki T, Janisiewicz AM, Clark E, Nishino S, Scammell TE. Kantor S, et al. Sleep. 2009 Sep;32(9):1127-34. doi: 10.1093/sleep/32.9.1127. Sleep. 2009. PMID: 19750917 Free PMC article.
• Designer receptor manipulations reveal a role of the locus coeruleus noradrenergic system in isoflurane general anesthesia.
  Vazey EM, Aston-Jones G. Vazey EM, et al. Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3859-64. doi: 10.1073/pnas.1310025111. Epub 2014 Feb 24. Proc Natl Acad Sci U S A. 2014. PMID: 24567395 Free PMC article.

Publication types

MeSH terms

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database