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

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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.

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Shanaz Diessler

Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
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.
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.
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.
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.

"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).

Copyright

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.