Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'

  1. Benjamin Roland
  2. Rebecca Jordan
  3. Dara L Sosulski
  4. Assunta Diodato
  5. Izumi Fukunaga
  6. Ian Wickersham
  7. Kevin M Franks
  8. Andreas T Schaefer
  9. Alexander Fleischmann  Is a corresponding author
  1. Collège de France, France
  2. The Francis Crick Institute, United Kingdom
  3. University College London, United Kingdom
  4. Massachusetts Institute of Technology, United States
  5. Duke University, United States

Abstract

Perturbations in neural circuits can provide mechanistic understanding of the neural correlates of behavior. In M71 transgenic mice with a 'monoclonal nose', glomerular input patterns in the olfactory bulb are massively perturbed and olfactory behaviors are altered. To gain insights into how olfactory circuits can process such degraded inputs we characterized odor-evoked responses of olfactory bulb mitral cells and interneurons. Surprisingly, calcium imaging experiments reveal that mitral cell responses in M71 transgenic mice are largely normal, highlighting a remarkable capacity of olfactory circuits to normalize sensory input. In vivo whole cell recordings suggest that feedforward inhibition from olfactory bulb periglomerular cells can mediate this signal normalization. Together, our results identify inhibitory circuits in the olfactory bulb as a mechanistic basis for many of the behavioral phenotypes of mice with a 'monoclonal nose' and highlight how substantially degraded odor input can be transformed to yield meaningful olfactory bulb output.

Article and author information

Author details

  1. Benjamin Roland

    Center for Interdisciplinary Research in Biology, Collège de France, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Rebecca Jordan

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Dara L Sosulski

    Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Assunta Diodato

    Center for Interdisciplinary Research in Biology, Collège de France, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Izumi Fukunaga

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Ian Wickersham

    MIT Genetic Neuroengineering Group, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kevin M Franks

    Department of Neurobiology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Andreas T Schaefer

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Alexander Fleischmann

    Center for Interdisciplinary Research in Biology, Collège de France, Paris, France
    For correspondence
    alexander.fleischmann@college-de-france.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Upinder S Bhalla, National Centre for Biological Sciences, India

Ethics

Animal experimentation: All experiments were performed in accordance with approved institutional animal care and use committee protocols of Columbia University (#AC-AAAH9255), and in accordance with the INSERM Animal Care and Use Committee guidelines (#B750512/00615.02), the German Animal Welfare Act, and the UK Home Office and the Animals and Scientific Procedures Act (#PPL 70/7827).

Version history

  1. Received: March 23, 2016
  2. Accepted: May 12, 2016
  3. Accepted Manuscript published: May 13, 2016 (version 1)
  4. Version of Record published: June 23, 2016 (version 2)
  5. Version of Record updated: June 29, 2016 (version 3)

Copyright

© 2016, Roland 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

  • 2,924
    views
  • 720
    downloads
  • 35
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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)

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

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

  1. Benjamin Roland
  2. Rebecca Jordan
  3. Dara L Sosulski
  4. Assunta Diodato
  5. Izumi Fukunaga
  6. Ian Wickersham
  7. Kevin M Franks
  8. Andreas T Schaefer
  9. Alexander Fleischmann
(2016)
Massive normalization of olfactory bulb output in mice with a 'monoclonal nose'
eLife 5:e16335.
https://doi.org/10.7554/eLife.16335

Share this article

https://doi.org/10.7554/eLife.16335

Further reading

    1. Neuroscience
    Yali Pan, Steven Frisson ... Ole Jensen
    Research Article

    Humans can read and comprehend text rapidly, implying that readers might process multiple words per fixation. However, the extent to which parafoveal words are previewed and integrated into the evolving sentence context remains disputed. We investigated parafoveal processing during natural reading by recording brain activity and eye movements using MEG and an eye tracker while participants silently read one-line sentences. The sentences contained an unpredictable target word that was either congruent or incongruent with the sentence context. To measure parafoveal processing, we flickered the target words at 60 Hz and measured the resulting brain responses (i.e. Rapid Invisible Frequency Tagging, RIFT) during fixations on the pre-target words. Our results revealed a significantly weaker tagging response for target words that were incongruent with the previous context compared to congruent ones, even within 100ms of fixating the word immediately preceding the target. This reduction in the RIFT response was also found to be predictive of individual reading speed. We conclude that semantic information is not only extracted from the parafovea but can also be integrated with the previous context before the word is fixated. This early and extensive parafoveal processing supports the rapid word processing required for natural reading. Our study suggests that theoretical frameworks of natural reading should incorporate the concept of deep parafoveal processing.

    1. Neuroscience
    Jack W Lindsey, Elias B Issa
    Research Article

    Object classification has been proposed as a principal objective of the primate ventral visual stream and has been used as an optimization target for deep neural network models (DNNs) of the visual system. However, visual brain areas represent many different types of information, and optimizing for classification of object identity alone does not constrain how other information may be encoded in visual representations. Information about different scene parameters may be discarded altogether (‘invariance’), represented in non-interfering subspaces of population activity (‘factorization’) or encoded in an entangled fashion. In this work, we provide evidence that factorization is a normative principle of biological visual representations. In the monkey ventral visual hierarchy, we found that factorization of object pose and background information from object identity increased in higher-level regions and strongly contributed to improving object identity decoding performance. We then conducted a large-scale analysis of factorization of individual scene parameters – lighting, background, camera viewpoint, and object pose – in a diverse library of DNN models of the visual system. Models which best matched neural, fMRI, and behavioral data from both monkeys and humans across 12 datasets tended to be those which factorized scene parameters most strongly. Notably, invariance to these parameters was not as consistently associated with matches to neural and behavioral data, suggesting that maintaining non-class information in factorized activity subspaces is often preferred to dropping it altogether. Thus, we propose that factorization of visual scene information is a widely used strategy in brains and DNN models thereof.