Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala

Abstract

Itch is an unpleasant sensation that elicits robust scratching and aversive experience. However, the identity of the cells and neural circuits that organize this information remains elusive. Here we show the necessity and sufficiency of chloroquine-activated neurons in the central amygdala (CeA) for both itch sensation and associated aversion. Further, we show that chloroquine-activated CeA neurons play important roles in itch-related comorbidities, including anxiety-like behaviors, but not in some aversive and appetitive behaviors previously ascribed to CeA neurons. RNA-sequencing of chloroquine-activated CeA neurons identified several differentially expressed genes as well as potential key signaling pathways in regulating pruritis. Finally, viral tracing experiments demonstrate that these neurons send projections to the ventral periaqueductal gray that are critical in modulation of itch. These findings reveal a cellular and circuit signature of CeA neurons orchestrating behavioral and affective responses to pruritus in mice.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE130268

The following data sets were generated

Article and author information

Author details

  1. Vijay K Samineni

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9491-2793
  2. Jose G Grajales-Reyes

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gary E Grajales-Reyes

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Eric Dameon Tycksen

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6362-0141
  5. Bryan A Copits

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Christian Pedersen

    Bioengineering, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Edem S Ankudey

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Julian N Sackey

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sienna B Sewell

    Washington University in St Louis, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Michael R Bruchas

    Anesthesiology and Pain Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4713-7816
  11. Robert W Gereau IV

    Washington University in St Louis, St Louis, United States
    For correspondence
    gereaur@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5428-4251

Funding

National Institute of Neurological Disorders and Stroke (R01NS106953)

  • Robert W Gereau IV

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116178)

  • Robert W Gereau IV

National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK115634)

  • Vijay K Samineni

National Institute of Neurological Disorders and Stroke (5F31NS103472-02)

  • Jose G Grajales-Reyes

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128475)

  • Vijay K Samineni

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

Reviewing Editor

  1. Mario Penzo, National Institute of Mental Health, United States

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) of Washington University School of Medicine (approved protocol 20-0078).

Version history

  1. Received: March 5, 2021
  2. Accepted: May 24, 2021
  3. Accepted Manuscript published: May 25, 2021 (version 1)
  4. Version of Record published: June 2, 2021 (version 2)

Copyright

© 2021, Samineni 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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  1. Vijay K Samineni
  2. Jose G Grajales-Reyes
  3. Gary E Grajales-Reyes
  4. Eric Dameon Tycksen
  5. Bryan A Copits
  6. Christian Pedersen
  7. Edem S Ankudey
  8. Julian N Sackey
  9. Sienna B Sewell
  10. Michael R Bruchas
  11. Robert W Gereau IV
(2021)
Cellular, circuit and transcriptional framework for modulation of itch in the central amygdala
eLife 10:e68130.
https://doi.org/10.7554/eLife.68130

Share this article

https://doi.org/10.7554/eLife.68130

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