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

Jordan G. McCall, Ream Al-Hasani, Edward R. Siuda, Daniel Y. Hong, Aaron J. Norris, Christopher P. Ford, Michael R. Bruchas

Research output: Contribution to journalArticlepeer-review

301 Scopus citations


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 invivo chemogenetics, optogenetics, and retrograde tracing, we determine that increased tonic activity ofthe LC-NE system is necessary and sufficient forstress-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.

Original languageEnglish
Pages (from-to)605-620
Number of pages16
Issue number3
StatePublished - Aug 5 2015


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