TY - JOUR
T1 - CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety
AU - McCall, Jordan G.
AU - Al-Hasani, Ream
AU - Siuda, Edward R.
AU - Hong, Daniel Y.
AU - Norris, Aaron J.
AU - Ford, Christopher P.
AU - Bruchas, Michael R.
N1 - Funding Information:
This work is supported by the National Institute on Drug Abuse (NIDA) R21 DA035144 (M.R.B.), McDonnell Center for Systems Neuroscience (M.R.B.), NIDA R01 DA035821 (C.P.F.), NIMH F31 MH101956 (J.G.M.), NIDA K99 DA038725 (R.A.), and Washington University School of Medicine Division of Biological and Biomedical Sciences (J.G.M.). We thank the M.R.B laboratory, in particular Blessan Sebastian, William Planer, Audra Foshage, and Lamley Lawson, for helpful insights, discussions, and technical support. We especially thank Robert W. Gereau IV, Erik D. Herzog, Timothy E. Holy, Joseph D. Dougherty, and Vijay K. Samineni for helpful discussions. We thank Karl Deisseroth (Stanford University) for the channelrhodopsin-2 (H134) construct, Garret Stuber (University of North Carolina) for the Th-IRES-Cre mice, and Max Kelz (University of Pennsylvania) for the Gal-Cre mice. We also thank The Washington University School of Medicine HOPE Center viral vector core (National Institute of Neurological Disorders and Stroke [NINDS], P30NS057105) and Bakewell Neuroimaging Laboratory.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/8/5
Y1 - 2015/8/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84938749925&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2015.07.002
DO - 10.1016/j.neuron.2015.07.002
M3 - Article
C2 - 26212712
AN - SCOPUS:84938749925
VL - 87
SP - 605
EP - 620
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 3
ER -