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Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use., Competing Interests: RJL has received research grant funding from Philips Lighting/Signify and honoraria from Samsung Electronics. GCB has received research grant funding from the Nova Institute, Toshiba Materials Science, Seoul Semiconductor, BIOS, Robern, and PhotoPharmics Inc. He has a current patent (USPTO 7678140 B2) that is licensed by Litebook Company Ltd. He is a paid member of the PhotoPharmics Scientific Advisory Board; has been a paid consultant by Lutron, Inc. and McCullough Hill LLC; and has received honoraria from the Institute for Functional Medicine. BNG has received funding from Tecniplast to travel and present at a symposium. RAH has received research grant funding from Philips Lighting/Signify and is a scientific advisor for the Good Light Group and Chrono@Work. JST is a co-founder and SAB member of Synchronicity Pharma. SNP has received consulting fees from NASA Ames and Sleep Standards., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Prevailing patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, international standard provides a SI-compliant way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert scientific consensus and expressed in an easily measured quantity (melanopic equivalent daylight illuminance (melaponic EDI)) defined within this standard. The recommendations are supported by detailed analysis of the sensitivity of human circadian, neuroendocrine, and alerting responses to ocular light and provide a straightforward framework to inform lighting design and practice., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GCB was supported, in part, by DOE grant DE- EE0008207, NAS Award #HR 05-23 UNIT 905; NASA grant NNX15AC14G; the NSF ERC LESA Center; BIOS, Toshiba Materials Science, The Nova Institute (The Institute for Integrative Health) and the Philadelphia Section of the Illuminating Engineering Society. GCB reports having issued (USPTO 7,678,140 and 8,366,755) and pending (USPTO 16/252,300, 15/085,522 and 14/273,971) patents related to the photoreceptor system for melatonin regulation. That intellectual property has been licensed by Litebook Company Ltd. He has been a paid consultant by Lutron, Inc., and McCullough Hill LLC. In addition, he and his research program have received financial, material and travel support from a range of federal, industrial, legal and philanthropic organizations in the past and present. CC has received consulting, honoraria, travel, accommodation and/or subsistence fees for invited keynote lectures, conference presentations or teaching from Toshiba Materials, Velux, Firalux, Lighting Europe, Electrosuisse, Novartis, Roche, Elite, Servier, and WIR Bank. CC is a member of the Daylight Academy. CAC reports grants to BWH from FAA, NHLBI, NIA, NIOSH, NASA, and DOD; is/was a paid consultant to AARP (2018), American Academy of Dental Sleep Medicine (2017, 2018), Eisenhower Medical Center (2018), Emory University (2019), Ganésco, Inc. (2017), Inselspital Bern (2019), Institute of Digital Media and Child Development (2017, 2018, 2019), Klarman Family Foundation (2017, 2018, 2019), M. Davis and Co (2018), Physician’s Seal (2019), Samsung (2016), Sleep Research Society Foundation (2019), State of Washington Board of Pilotage Commissioners (2018), Tencent Holdings Ltd (2019), Teva Pharma Australia (2019, 2020), UC San Diego (2018), University of Michigan (2017), University of Washington (2017, 2018), and Vanda Pharmaceuticals Inc (2017, 2018, 2019, 2020), in which CAC also holds an equity interest; received travel support from Annenberg Center for Health Sciences at Eisenhower (2018), Aspen Brain Institute (2018), Bloomage International Investment Group, Inc. (2018, 2019), UK Biotechnology and Biological Sciences Research Council (2019), Bouley Botanical (2017, 2018, 2019), Dr. Stanley Ho Medical Development Foundation (2019), European Biological Rhythms Society (2017, 2019), German National Academy of Sciences (Leopoldina) (2019), Illuminating Engineering Society (2018), National Safety Council (2017, 2018, 2019), National Sleep Foundation (2017, 2018, 2019), Society for Research on Biological Rhythms (2018), Sleep Research Society Foundation (2018), Stanford Medical School Alumni Association (2019), Tencent Holdings Ltd (2019), University of Zurich (2018), and Vanda Pharmaceuticals Inc (2017, 2018, 2019), Ludwig-Maximilians-Universität München (2018), National Highway Transportation Safety Administration (2018), Office of Naval Research (2018), Salk Institute for Biological Studies/Fondation Ipsen (2018), The National Academy of Sciences, Engineering, and Medicine (2017), The Wonderful Company (2017), Department of Defense (2017); receives research/education support through BWH from Cephalon, Mary Ann & Stanley Snider via Combined Jewish Philanthropies, Harmony Biosciences LLC (2019, 2020), Jazz Pharmaceuticals PLC Inc (2017, 2018, 2019, 2020), Johnson & Johnson (2019), NeuroCare, Inc. (2019), Philips Respironics Inc/Philips Homecare Solutions (2017, 2 018, 2019, 2020), Regeneron Pharmaceuticals (2018, 2019, 2020), Regional Home Care (2019), Teva Pharmaceuticals Industries Ltd, Sanofi SA, Optum, ResMed, San Francisco Bar Pilots, Sanofi, Schneider, Simmons, Sysco, Philips, Vanda Pharmaceuticals; is/was an expert witness in legal cases, including those involving Advanced Power Technologies, Aegis Chemical Solutions LLC (2019), Amtrak (2019); Casper Sleep Inc (2019), C&J Energy Services (2019), Complete General Construction Co (2017), Dallas Police Association (2019), Enterprise Rent-A-Car (2019), Espinal Trucking/Eagle Transport Group LLC/Steel Warehouse Inc (2017, 2018, 2019), FedEx, Greyhound Lines Inc/Motor Coach Industries/FirstGroup America (2017, 2018, 2019), Pomerado Hospital/Palomar Health District (2017, 2018), PAR Electrical Contractors Inc (2019), Product & Logistics Services LLC/Schlumberger Technology Corp/Gelco Fleet Trust (2019), Puckett Emergency Medical Services LLC (2019), South Carolina Central Railroad Company LLC (2017, 2018), Union Pacific Railroad (2019), United Parcel Service/UPS Ground Freight Inc (2017, 2018), and Vanda Pharmaceuticals (2019, 2020); serves as the incumbent of an endowed professorship provided to Harvard University by Cephalon, Inc.; and receives royalties from McGraw Hill, and Philips Respironics (2017, 2018, 2019, 2020) for the Actiwatch-2 and Actiwatch Spectrum devices. CACs interests were reviewed and are managed by the Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict of interest policies. SWL has received consulting fees from Atlanta Falcons, Atlanta Hawks, BHP Billiton, Delos Living LLC, EyeJust Inc., McCullough Hill Leary PS, Noble Insights, OpTerra Energy Services Inc., Pegasus Capital Advisors, Phillips Lytle LLP, Plan LED, Rec Room, Serrado Capital, Slingshot Insights, Stantec and Team C Racing. He has current consulting contracts with Akili Interactive, Apex 2100 Ltd, Consumer Sleep Solutions, Headwaters Inc., Hintsa Performance AG, KBR Wyle Services, Light Cognitive, Lighting Science Group Corporation/HealthE, Look Optic, Mental Workout/Timeshifter, Paul Weiss Rifkind Wharton & Garrison LLP, Six Senses, and View Inc. SWL has received unrestricted equipment gifts from Bionetics Corporation and F.LUX Software LLC; a fellowship gift from Stockgrand Ltd; has equity in iSLEEP, Pty; royalties from Oxford University Press; honoraria plus travel, accommodation and/or meals for invited seminars, conference presentations or teaching from Estée Lauder, Ineos, Informa Exhibitions, MIT, Roxbury Latin School, and Teague; travel, accommodation and/or meals only (no honoraria) for invited seminars, conference presentations, teaching or editorial duties from DIN, Emory University, Lightfair, SLTBR, Solemma and Wiley. SWL has an ongoing investigator-initiated grant from F. Lux Software LLC and a Clinical Research Support Agreement from Vanda Pharmaceuticals Inc. SWL holds a process patent for ‘Systems and methods for determining and/or controlling sleep quality’, which is assigned to the Brigham and Women’s Hospital per Hospital policy, and ‘Method and system for generating and providing notifications for a circadian shift protocol’ held by Mental Workout Inc. SWL has served as a paid expert in legal proceedings related to light, health and work patterns. SWL was the Program Leader for ‘Safety and Productivity Improvements’ in the CRC for Alertness, Safety and Productivity from 2015-2019, through a part-time Adjunct Professor appointment at Monash University, Australia. SWL’s interests are reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. RJL and TMB have received research funding from Signify (formerly Philips Lighting). RJL has received speaker fees from Samsung. RJL, LP, LJMS and MS have served as members of the CIE Joint Technical Committee 9 on the definition of CIE S 026:2018. These were unpaid roles. JPH was supported, in part, by DOE grant DE- EE0008207, NAS Award #HR 05-23 UNIT 905; NASA grant NNX15AC14G; NSF Award #2037357; Rensselaer Polytechnic Institute; BIOS, Toshiba Materials Science, The Institute for Integrative Health; and the Philadelphia Section of the Illuminating Engineering Society. He has been a paid consultant by Lutron, Inc. and McCullough Hill LLC. MM is an unpaid founding member of the Daylight Academy (DLA). SNP reports no conflicting interests. JOH, In addition to paid employment with Public Health England, is Vice-President Standards of the CIE, a member of the Scientific Expert Group of the International Commission on Non-Ionizing Radiation Protection and a number of their Project Groups, Co-Convenor of an ISO committee on Integrative Lighting, a member of two committees of the Illuminating Engineering Society of North America, Convenor of an IEC committee and a member of a Core Group for the World Health Organization, all as unpaid roles. LP served as the CIE reporter to CIE TN 003:2015 on the first Manchester Workshop in 2013, is currently serving as Director and as Secretary of the CIE Division “Photobiology and Photochemistry”, as the CIE reporter on the CIE S 026 Toolbox (doi.org/10.25039/S026.2018.TB), as a member of CIE Joint Technical Committee 14 (working with ISO Joint Working Group 4) on Integrative Lighting, and as the CIE reporter on the second Manchester Workshop 2019 (attended by all the authors), all as unpaid roles LJMS’s full time position at Eindhoven University has been partially funded by Signify, he is also active in various unpaid roles within the International Commission on Illumination (CIE). DJS is a co-inventor on issued patents (EP1614441A1 and WO2015052207A1), a Founding member of the Daylight Academy and reports receiving research support from BBSRC and EU H2020-SC1-2020-Two-Stage-RTD, ENLIGHTENme, Innovative policies for improving citizens’ health and wellbeing addressing indoor and outdoor lighting (No. 945238). CV is an unpaid member of the Circadian Light Therapy (Inc.) and the Chronsulting Scientific Advisory Boards. In addition, CV’s research and scholarship is funded by the University of Colorado Boulder, the Colorado Clinical and Translational Sciences Institute, the National Institutes of Health, and the Department of Energy. MS is currently an unpaid member of CIE Technical Committee TC 1-98 ("A Roadmap Toward Basing CIE Colorimetry on Cone Fundamentals"). MS was an unpaid advisor to the Division Reportership DR 6-45 of Division 3 ("Publication and maintenance of the CIE S026 Toolbox"). Between 2017 and 2020, MS was elected Chair of the Color Technical Group within the Optical Society. Since 2020, MS is an elected member of the Daylight Academy, an unpaid member of the Board of Advisors of the Center for Environmental Therapeutics, and MS is a member of the Technical Advisory Board of Faurecia IRYStec Inc. Over the past two years (2019-2020), MS has received industrial research support from f.lux software LLC, Ocean Insight, and BIOS Lighting. MS reports funding from the Wellcome Trust, the Royal Society, EPSRC, Bioscientifica Trust, Fight for Sight, Freie Akademische Gesellschaft Basel, and the University of Oxford. PCZ reports funding from National Institutes of Health, Eisai, Philips, Jazz Pharmaceuticals, Technogel, Harmony Biosciences, Apnimed, X – a Division of Alphabet, Inc., Merck and Sanofi. In addition, PCZ has patent applications pending (62/038700; 15/517458). KPW reports during the conduct of the 2nd International Workshop and preparation of this manuscript being a board member of the Sleep Research Society; chair of the American Academy of Sleep Medicine Clinical Practice Guideline for the Treatment of Adults with Shift Work Disorder and Jet Lag Disorder Workgroup; receiving research support from the NIH, the Office of Naval Research, the PAC-12 conference, and consulting for Circadian Therapeutics, LTD., Circadian Biotherapies, Inc. Philips Respironics, U.S. Army Medical Research and Materiel Command-Walter Reed Army Institute of Research outside the submitted work.

Light plays a critical role in the regulation of numerous aspects of physiology and behaviour, including the entrainment of circadian rhythms and the regulation of sleep. These responses involve melanopsin (OPN4)-expressing photosensitive retinal ganglion cells (pRGCs) in addition to rods and cones. Nocturnal light exposure in rodents has been shown to result in rapid sleep induction, in which melanopsin plays a key role. However, studies have also shown that light exposure can result in elevated corticosterone, a response that is not compatible with sleep. To investigate these contradictory findings and to dissect the relative contribution of pRGCs and rods/cones, we assessed the effects of light of different wavelengths on behaviourally defined sleep. Here, we show that blue light (470 nm) causes behavioural arousal, elevating corticosterone and delaying sleep onset. By contrast, green light (530 nm) produces rapid sleep induction. Compared to wildtype mice, these responses are altered in melanopsin-deficient mice (Opn4-/-), resulting in enhanced sleep in response to blue light but delayed sleep induction in response to green or white light. We go on to show that blue light evokes higher Fos induction in the SCN compared to the sleep-promoting ventrolateral preoptic area (VLPO), whereas green light produced greater responses in the VLPO. Collectively, our data demonstrates that nocturnal light exposure can have either an arousal- or sleep-promoting effect, and that these responses are melanopsin-mediated via different neural pathways with different spectral sensitivities. These findings raise important questions relating to how artificial light may alter behaviour in both the work and domestic setting.

Sleep and/or circadian rhythm disruption (SCRD) is seen in up to 80% of schizophrenia patients. The co-morbidity of schizophrenia and SCRD may in part stem from dysfunction in common brain mechanisms, which include the glutamate system, and in particular, the group II metabotropic glutamate receptors mGlu2 and mGlu3 (encoded by the genes Grm2 and Grm3). These receptors are relevant to the pathophysiology and potential treatment of schizophrenia, and have also been implicated in sleep and circadian function. In the present study, we characterised the sleep and circadian rhythms of Grm2/3 double knockout (Grm2/3-/-) mice, to provide further evidence for the involvement of group II metabotropic glutamate receptors in the regulation of sleep and circadian rhythms. We report several novel findings. Firstly, Grm2/3-/- mice demonstrated a decrease in immobility-determined sleep time and an increase in immobility-determined sleep fragmentation. Secondly, Grm2/3-/- mice showed heightened sensitivity to the circadian effects of light, manifested as increased period lengthening in constant light, and greater phase delays in response to nocturnal light pulses. Greater light-induced phase delays were also exhibited by wildtype C57Bl/6J mice following administration of the mGlu2/3 negative allosteric modulator RO4432717. These results confirm the involvement of group II metabotropic glutamate receptors in photic entrainment and sleep regulation pathways. Finally, the diurnal wheel-running rhythms of Grm2/3-/- mice were perturbed under a standard light/dark cycle, but their diurnal rest-activity rhythms were unaltered in cages lacking running wheels, as determined with passive infrared motion detectors. Hence, when assessing the diurnal rest-activity rhythms of mice, the choice of assay can have a major bearing on the results obtained.

Photosensitive retinal ganglion cells (pRGCs) respond to light from birth and represent the earliest known light detection system to develop in the mouse retina. A number of morphologically and functionally distinct subtypes of pRGCs have been described in the adult retina, and have been linked to different physiological roles. We have previously identified two distinct isoforms of mouse melanopsin, Opn4L and Opn4S, which are generated by alternate splicing of the Opn4 locus. These isoforms are differentially expressed in pRGC subtypes of the adult mouse retina, with both Opn4L and Opn4S detected in M1 type pRGCs, and only Opn4L detected in M2 type pRGCs. Here we investigate the developmental expression of Opn4L and Opn4S and show a differential profile of expression during postnatal development. Opn4S mRNA is detected at relatively constant levels throughout postnatal development, with levels of Opn4S protein showing a marked increase between P0 and P3, and then increasing progressively over time until adult levels are reached by P10. By contrast, levels of Opn4L mRNA and protein are low at birth and show a marked increase at P14 and P30 compared to earlier time points. We suggest that these differing profiles of expression are associated with the functional maturation of M1 and M2 subtypes of pRGCs. Based upon our data, Opn4S expressing M1 type pRGCs mature first and are the dominant pRGC subtype in the neonate retina, whereas increased expression of Opn4L and the maturation of M2 type pRGCs occurs later, between P10 and P14, at a similar time to the maturation of rod and cone photoreceptors. We suggest that the distinct functions associated with these cell types will develop at different times during postnatal development.