Neuron
Volume 87, Issue 3, 5 August 2015, Pages 605-620
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Article
CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety

https://doi.org/10.1016/j.neuron.2015.07.002Get rights and content
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Highlights

  • Inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior

  • Increased tonic LC-NE neuronal activity promotes anxiety-like and aversive behavior

  • CRH+ CeA-LC projections increase LC-NE activity and promote anxiogenic responses

  • CRH+ CeA-LC-induced anxiety-like behavior is mediated by CRHR1 receptors

Summary

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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