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
ISSN1097-4199
AutoresJordan 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
ResumoSummary 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.
Referência(s)