title: CRH Engagement of the Locus Coeruleus Noradrenergic System Mediates Stress-Induced Anxiety.
abstract: 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.
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Jordan G
authors.initials: JG
authors.lastname: McCall
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Ream
authors.initials: R
authors.lastname: Al-Hasani
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Siuda
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Hong
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Norris
authors.affiliation: Department of Physiology and Biophysics, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Ford
authors.affiliation: Division of Basic Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Washington University Pain Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: bruchasm@wustl.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bruchas
mesh_terms: D059331:Adrenergic Neurons / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D008125:Locus Coeruleus / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D062308:Optogenetics / Q000379:methods; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine