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Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

  1. Jordan G McCall
  2. Edward R Siuda
  3. Dionnet L Bhatti
  4. Lamley A Lawson
  5. Zoe A McElligott
  6. Garret D Stuber
  7. Michael R Bruchas Is a corresponding author
  1. Washington University School of Medicine, United States
  2. University of North Carolina, United States
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Cite as: eLife 2017;6:e18247 doi: 10.7554/eLife.18247

Abstract

Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms.

Article and author information

Author details

  1. Jordan G McCall

    1. Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon 0000-0001-8295-0664
  2. Edward R Siuda

    1. Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
    Competing interests
    No competing interests declared.
  3. Dionnet L Bhatti

    1. Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
    Competing interests
    No competing interests declared.
  4. Lamley A Lawson

    1. Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
    Competing interests
    No competing interests declared.
  5. Zoe A McElligott

    1. Department of Psychiatry, University of North Carolina, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  6. Garret D Stuber

    1. Department of Psychiatry, University of North Carolina, Chapel Hill, United States
    Competing interests
    No competing interests declared.
  7. Michael R Bruchas

    1. Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, United States
    For correspondence
    1. bruchasm@wustl.edu
    Competing interests
    Michael R Bruchas, Michael R. Bruchas, PhD is a co-founder of Neurolux, Inc, a company that is making wireless optogenetic and various neuroscience-related probes. None of the work in this manuscript used these devices or is related to any of the company's activities, but we list this information here in full disclosure..
    ORCID icon 0000-0003-4713-7816

Funding

National Institute on Drug Abuse (DA035144)

  • Michael R Bruchas

McDonnell Center for Systems Neuroscience

  • Michael R Bruchas

National Institute of Mental Health (MH101956)

  • Jordan G. McCall

Washington University in St. Louis

  • Jordan G. McCall
  • Edward R Siuda

National Institute on Alcohol Abuse and Alcoholism (AA023555)

  • Zoe A McElligott

Alcohol Beverage Medical Research Foundation

  • Zoe A McElligott

National Institute of Mental Health (MH112355)

  • Michael R Bruchas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols at Washington University in St. Louis. The protocol was approved by the Animal Studies Committee at Washington University in St. Louis (Protocol Number: 20130219; expiration date: 15/10/2016). All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Liqun Luo, Reviewing Editor, Howard Hughes Medical Institute, Stanford University, United States

Publication history

  1. Received: May 27, 2016
  2. Accepted: July 13, 2017
  3. Accepted Manuscript published: July 14, 2017 (version 1)

Copyright

© 2017, McCall et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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