1. Neuroscience
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Rai1 frees mice from the repression of active wake behaviors by light

  1. Shanaz Diessler
  2. Corinne Kostic
  3. Yvan Arsenijevic
  4. Aki Kawasaki
  5. Paul Franken  Is a corresponding author
  1. University of Lausanne, Switzerland
Research Article
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Cite this article as: eLife 2017;6:e23292 doi: 10.7554/eLife.23292

Abstract

Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka 'masking') mechanisms. In Smith-Magenis Syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggest impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output.

Article and author information

Author details

  1. Shanaz Diessler

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Corinne Kostic

    Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Yvan Arsenijevic

    Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Aki Kawasaki

    Jules-Gonin Eye Hospital, Fondation Asile des Aveugles, University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul Franken

    Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
    For correspondence
    paul.franken@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2500-2921

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII3_136201,31003A_146694)

  • Paul Franken

State of Vaud, Switzerland

  • Paul Franken

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 experiments were approved by the Ethical Committee of the State of Vaud Veterinary Office, Switzerland (# VD2545).

Reviewing Editor

  1. Louis J Ptáček, University of California, San Francisco, United States

Publication history

  1. Received: November 16, 2016
  2. Accepted: May 24, 2017
  3. Accepted Manuscript published: May 26, 2017 (version 1)
  4. Version of Record published: June 8, 2017 (version 2)
  5. Version of Record updated: June 9, 2017 (version 3)

Copyright

© 2017, Diessler 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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