1. Neuroscience
Download icon

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

Research Article
  • Cited 0
  • Views 595
  • Annotations
Cite this article as: eLife 2021;10:e68130 doi: 10.7554/eLife.68130

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.

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).

Reviewing Editor

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

Publication 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.

Metrics

  • 595
    Page views
  • 142
    Downloads
  • 0
    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
    Sahana Sitaraman et al.
    Research Article

    Gap junctions between neurons serve as electrical synapses, in addition to conducting metabolites and signaling molecules. During development, early-appearing gap junctions are thought to prefigure chemical synapses, which appear much later. We present evidence for this idea at a central, glutamatergic synapse and provide some mechanistic insights. Loss or reduction in the levels of the gap junction protein Gjd2b decreased the frequency of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in cerebellar Purkinje neurons (PNs) in larval zebrafish. Ultrastructural analysis in the molecular layer showed decreased synapse density. Further, mEPSCs had faster kinetics and larger amplitudes in mutant PNs, consistent with their stunted dendritic arbors. Time-lapse microscopy in wild type and mutant PNs reveals that Gjd2b puncta promote the elongation of branches and that CaMKII may be a critical mediator of this process. These results demonstrate that Gjd2b-mediated gap junctions regulate glutamatergic synapse formation and dendritic elaboration in PNs.

    1. Neuroscience
    Amicia D Elliott et al.
    Research Article Updated

    Identifying neural substrates of behavior requires defining actions in terms that map onto brain activity. Brain and muscle activity naturally correlate via the output of motor neurons, but apart from simple movements it has been difficult to define behavior in terms of muscle contractions. By mapping the musculature of the pupal fruit fly and comprehensively imaging muscle activation at single-cell resolution, we here describe a multiphasic behavioral sequence in Drosophila. Our characterization identifies a previously undescribed behavioral phase and permits extraction of major movements by a convolutional neural network. We deconstruct movements into a syllabary of co-active muscles and identify specific syllables that are sensitive to neuromodulatory manipulations. We find that muscle activity shows considerable variability, with sequential increases in stereotypy dependent upon neuromodulation. Our work provides a platform for studying whole-animal behavior, quantifying its variability across multiple spatiotemporal scales, and analyzing its neuromodulatory regulation at cellular resolution.