Rai1 frees mice from the repression of active wake behaviors by light
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
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.
Reviewing Editor
- Louis J Ptáček, University of California, San Francisco, United States
Ethics
Animal experimentation: All experiments were approved by the Ethical Committee of the State of Vaud Veterinary Office, Switzerland (# VD2545).
Version history
- Received: November 16, 2016
- Accepted: May 24, 2017
- Accepted Manuscript published: May 26, 2017 (version 1)
- Version of Record published: June 8, 2017 (version 2)
- 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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