Artigo Acesso aberto Revisado por pares

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

2015; Cell Press; Volume: 87; Issue: 3 Linguagem: Inglês

10.1016/j.neuron.2015.07.002

ISSN

1097-4199

Autores

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

Tópico(s)

Neuroscience and Neuropharmacology Research

Resumo

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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