1. Neuroscience
Download icon

Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats

  1. Stefan Hirschberg
  2. Yong Li
  3. Andrew Randall
  4. Eric J Kremer
  5. Anthony E Pickering  Is a corresponding author
  1. University of Bristol, United Kingdom
  2. University of Exeter, United Kingdom
  3. CNRS, France
Research Article
  • Cited 56
  • Views 3,039
  • Annotations
Cite this article as: eLife 2017;6:e29808 doi: 10.7554/eLife.29808

Abstract

The locus coeruleus (LC) projects throughout the brain and spinal cord and is the major source of central noradrenaline. It remains unclear whether the LC acts functionally as a single global effector or as discrete modules. Specifically, while spinal-projections from LC neurons can exert analgesic actions, it is not known whether they can act independently of ascending LC projections. Using viral vectors taken up at axon terminals, we expressed chemogenetic actuators selectively in LC neurons with spinal (LC:SC) or prefrontal cortex (LC:PFC) projections. Activation of the LC:SC module produced robust, lateralised anti-nociception while activation of LC:PFC produced aversion. In a neuropathic pain model, LC:SC activation reduced hind-limb sensitization and induced conditioned place preference. By contrast, activation of LC:PFC exacerbated spontaneous pain, produced aversion and increased anxiety-like behaviour. This independent, contrasting modulation of pain-related behaviours mediated by distinct noradrenergic neuronal populations provides evidence for a modular functional organisation of the LC.

Article and author information

Author details

  1. Stefan Hirschberg

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Yong Li

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrew Randall

    Institute of Biomedical and Clinical Sciences, University of Exeter, Exeter, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Eric J Kremer

    IGMM, CNRS, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Anthony E Pickering

    School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
    For correspondence
    tony.pickering@bristol.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0345-0456

Funding

Wellcome (gr088373)

  • Anthony E Pickering

University of Bristol

  • Stefan Hirschberg
  • Andrew Randall
  • Anthony E Pickering

European Molecular Biology Organization

  • Stefan Hirschberg
  • Eric J Kremer
  • Anthony E Pickering

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

Ethics

Animal experimentation: All procedures conformed to the UK Animals (Scientific Procedures) Act 1986, were performed under Home Office project licence (3003362) and were approved by the University of Bristol Animal Welfare and Ethical Review Board.

Reviewing Editor

  1. Allan Basbaum, University of California, San Francisco, United States

Publication history

  1. Received: June 21, 2017
  2. Accepted: October 11, 2017
  3. Accepted Manuscript published: October 13, 2017 (version 1)
  4. Version of Record published: October 23, 2017 (version 2)

Copyright

© 2017, Hirschberg 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.

Metrics

  • 3,039
    Page views
  • 618
    Downloads
  • 56
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Xiaoxuan Jia et al.
    Research Article

    Temporal continuity of object identity is a feature of natural visual input, and is potentially exploited -- in an unsupervised manner -- by the ventral visual stream to build the neural representation in inferior temporal (IT) cortex. Here we investigated whether plasticity of individual IT neurons underlies human core-object-recognition behavioral changes induced with unsupervised visual experience. We built a single-neuron plasticity model combined with a previously established IT population-to-recognition-behavior linking model to predict human learning effects. We found that our model, after constrained by neurophysiological data, largely predicted the mean direction, magnitude and time course of human performance changes. We also found a previously unreported dependency of the observed human performance change on the initial task difficulty. This result adds support to the hypothesis that tolerant core object recognition in human and non-human primates is instructed -- at least in part -- by naturally occurring unsupervised temporal contiguity experience.

    1. Neuroscience
    Nick Taubert et al.
    Research Article

    Dynamic facial expressions are crucial for communication in primates. Due to the difficulty to control shape and dynamics of facial expressions across species, it is unknown how species-specific facial expressions are perceptually encoded and interact with the representation of facial shape. While popular neural network models predict a joint encoding of facial shape and dynamics, the neuromuscular control of faces evolved more slowly than facial shape, suggesting a separate encoding. To investigate these alternative hypotheses, we developed photo-realistic human and monkey heads that were animated with motion capture data from monkeys and humans. Exact control of expression dynamics was accomplished by a Bayesian machine-learning technique. Consistent with our hypothesis, we found that human observers learned cross-species expressions very quickly, where face dynamics was represented largely independently of facial shape. This result supports the co-evolution of the visual processing and motor control of facial expressions, while it challenges appearance-based neural network theories of dynamic expression recognition.