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6 - Role of the locus coeruleus-norepinephrine system in arousal and circadian regulation of the sleep–wake cycle

from Part II - Norepinephrine and behavior

Published online by Cambridge University Press:  07 September 2009

Gary S. Aston-Jones Ph.D.
Affiliation:
University of Pennsylvania, Philadelphia, USA
Monica Gonzalez
Affiliation:
University of Pennsylvania, Philadelphia, USA
Scott Doran
Affiliation:
University of Pennsylvania, Philadelphia, USA
Gregory A. Ordway
Affiliation:
University of Mississippi
Michael A. Schwartz
Affiliation:
University of Hawaii, Manoa
Alan Frazer
Affiliation:
University of Texas Health Science Center, San Antonio
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Summary

Introduction

A variety of previous results indicate that the norepinephrine (NE) locus coeruleus (LC) system is integrally involved in regulation of sleep and waking. In particular, LC activation promotes wakefulness. This appears to be one of the major arousal systems in the brain. The LC was also found to be critical for rebound sleep following sleep deprivation, and increased sleep that occurs following a stressor. We recently identified a circuit from the suprachiasmatic nucleus (SCN) to the LC, in which the dorsomedial hypothalamus (DMH) serves as a relay. The functionality of this circuit was confirmed in our studies, showing that LC neurons have a circadian rhythm in their firing activity and that this circadian fluctuation in the LC requires an intact DMH. Other recent studies have also shown that lesions of the LC decrease the amplitude of the circadian rhythm in the sleep–wake cycle. These results indicate that the LC may be an important component in SCN efferent circuitry for driving circadian rhythms in sleep–wake cycles. Other recent results in our lab have revealed that light deprivation produces a profound loss of NE in the frontal cortex in rats, and this NE loss in dark-maintained animals is associated with decreased amplitude of the circadian sleep–wake rhythm. The dependence of the LC system on light for normal function has implications for clinical disorders such as seasonal affective disorder. Other disorders that are comorbid with sleep anomalies and associated with LC dysfunction are discussed.

Type
Chapter
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Brain Norepinephrine
Neurobiology and Therapeutics
, pp. 157 - 195
Publisher: Cambridge University Press
Print publication year: 2007

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