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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2015 Jul 28

PMID 26212712

Citations 279

Authors

Jordan G McCall

Ream Al-Hasani

Edward R Siuda

Daniel Y Hong

Aaron J Norris

Christopher P Ford

Michael R Bruchas

Affiliations

Soon will be listed here.

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.

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