Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb

  1. Shawn D Burton
  2. Audrey Brown
  3. Thomas P Eiting
  4. Isaac A Youngstrom
  5. Thomas C Rust
  6. Michael Schmuker
  7. Matt Wachowiak  Is a corresponding author
  1. University of Utah, United States
  2. University of Hertfordshire, United Kingdom

Abstract

In olfactory systems, convergence of sensory neurons onto glomeruli generates a map of odorant receptor identity. How glomerular maps relate to sensory space remains unclear. We sought to better characterize this relationship in the mouse olfactory system by defining glomeruli in terms of the odorants to which they are most sensitive. Using high-throughput odorant delivery and ultrasensitive imaging of sensory inputs, we imaged responses to 185 odorants presented at concentrations determined to activate only one or a few glomeruli across the dorsal olfactory bulb. The resulting datasets defined the tuning properties of glomeruli - and, by inference, their cognate odorant receptors - in a low-concentration regime, and yielded consensus maps of glomerular sensitivity across a wide range of chemical space. Glomeruli were extremely narrowly tuned, with ~25% responding to only one odorant, and extremely sensitive, responding to their effective odorants at sub-picomolar to nanomolar concentrations. Such narrow tuning in this concentration regime allowed for reliable functional identification of many glomeruli based on a single diagnostic odorant. At the same time, the response spectra of glomeruli responding to multiple odorants was best predicted by straightforward odorant structural features, and glomeruli sensitive to distinct odorants with common structural features were spatially clustered. These results define an underlying structure to the primary representation of sensory space by the mouse olfactory system.

Data availability

Data and code underlying all analyses, including response matrices for all imaged OBs and GUIs for interactively visualizing the datasets, are available from github.com/WachowiakLab and in the provided Source Data files.

Article and author information

Author details

  1. Shawn D Burton

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8907-6487
  2. Audrey Brown

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas P Eiting

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Isaac A Youngstrom

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas C Rust

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael Schmuker

    Department of Computer Science, University of Hertfordshire, Hatfield, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6753-4929
  7. Matt Wachowiak

    Department of Neurobiology, University of Utah, Salt Lake City, United States
    For correspondence
    matt.wachowiak@utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4508-9793

Funding

National Institutes of Health (NS109979)

  • Matt Wachowiak

National Institutes of Health (MH115448)

  • Shawn D Burton

National Science Foundation (1555919)

  • Matt Wachowiak

Medical Research Council (2014217)

  • Michael Schmuker

EU Human Brain Project (SGA3 945539)

  • Michael Schmuker

University of Utah (UROP Award)

  • Audrey Brown

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 were performed following the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the University of Utah Institutional Animal Care and Use Committee (IACUC protocols #19-06007, 19-06008).

Reviewing Editor

  1. Stephen Liberles, Harvard Medical School, United States

Publication history

  1. Preprint posted: May 12, 2022 (view preprint)
  2. Received: May 21, 2022
  3. Accepted: July 20, 2022
  4. Accepted Manuscript published: July 21, 2022 (version 1)
  5. Version of Record published: August 4, 2022 (version 2)

Copyright

© 2022, Burton 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. Shawn D Burton
  2. Audrey Brown
  3. Thomas P Eiting
  4. Isaac A Youngstrom
  5. Thomas C Rust
  6. Michael Schmuker
  7. Matt Wachowiak
(2022)
Mapping odorant sensitivities reveals a sparse but structured representation of olfactory chemical space by sensory input to the mouse olfactory bulb
eLife 11:e80470.
https://doi.org/10.7554/eLife.80470
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