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Neuron. 2015 Aug 5;87(3):605-20. doi: 10.1016/j.neuron.2015.07.002. Epub 2015 Jul 23.

CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.

Author information

1
Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Department of Physiology and Biophysics, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
5
Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: bruchasm@wustl.edu.

Abstract

The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing, we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin-releasing hormone(+) (CRH(+)) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders.

PMID:
26212712
PMCID:
PMC4529361
DOI:
10.1016/j.neuron.2015.07.002
[Indexed for MEDLINE]
Free PMC Article

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