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Article ; Online: Melanopic illuminance defines the magnitude of human circadian light responses under a wide range of conditions.

Brown, Timothy M

2020 Volume 69, Issue 1, Page(s) e12655

Abstract: Ocular light drives a range of nonvisual responses in humans including suppression of melatonin secretion and circadian phase resetting. These responses are driven by intrinsically photosensitive retinal ganglion cells (ipRGCs) which combine intrinsic, ... ...

Abstract	Ocular light drives a range of nonvisual responses in humans including suppression of melatonin secretion and circadian phase resetting. These responses are driven by intrinsically photosensitive retinal ganglion cells (ipRGCs) which combine intrinsic, melanopsin-based, phototransduction with extrinsic rod/cone-mediated signals. As a result of this arrangement, it has remained unclear how best to quantify light to predict its nonvisual effects. To address this, we analysed data from nineteen different laboratory studies that measured melatonin suppression, circadian phase resetting and/or alerting responses in humans to a wide array of stimulus types, intensities and durations with or without pupil dilation. Using newly established SI-compliant metrics to quantify ipRGC-influenced responses to light, we show that melanopic illuminance consistently provides the best available predictor for responses of the human circadian system. In almost all cases, melanopic illuminance is able to fully account for differences in sensitivity to stimuli of varying spectral composition, acting to drive responses that track variations in illumination characteristic of those encountered over civil twilight (~1-1000 lux melanopic equivalent daylight illuminance). Collectively, our data demonstrate widespread utility of melanopic illuminance as a metric for predicting the circadian impact of environmental illumination. These data therefore provide strong support for the use of melanopic illuminance as the basis for guidelines that seek to regulate light exposure to benefit human health and to inform future lighting design.
MeSH term(s)	Adult ; Circadian Rhythm ; Female ; Humans ; Light ; Lighting ; Male ; Melatonin/metabolism ; Middle Aged ; Retinal Ganglion Cells/metabolism ; Rod Opsins/metabolism
Chemical Substances	Rod Opsins ; melanopsin ; Melatonin (JL5DK93RCL)
Language	English
Publishing date	2020-04-19
Publishing country	England
Document type	Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12655
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Article ; Online: Beyond irradiance: Visual signals influencing mammalian circadian function.

Mouland, Joshua W / Brown, Timothy M

Progress in brain research

2022 Volume 273, Issue 1, Page(s) 145–169

Abstract: Daily changes in ambient illumination act as important time of day cues which are pivotal for aligning internal circadian clocks to external time. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), generally considered ... ...

Abstract	Daily changes in ambient illumination act as important time of day cues which are pivotal for aligning internal circadian clocks to external time. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), generally considered specialized for encoding light intensity (irradiance), are critical to this photoentrainment process. However, ipRGCs also convey information from conventional photoreceptor cells, the rods and cones. Here we review data from animal studies identifying the nature and roles of rod and cone signaling to the suprachiasmatic nucleus (SCN) circadian clock including evidence that visual features other than irradiance (color, spatiotemporal variations in light intensity) may influence photoentrainment or other SCN-dependent functions. Finally we consider the extent to which these findings from animal studies might similarly apply to human circadian function.
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Humans ; Light ; Mammals/metabolism ; Retinal Cone Photoreceptor Cells ; Retinal Ganglion Cells/metabolism ; Rod Opsins/metabolism ; Suprachiasmatic Nucleus/metabolism
Chemical Substances	Rod Opsins
Language	English
Publishing date	2022-05-31
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	1875-7855 ; 0079-6123
ISSN (online)	1875-7855
ISSN	0079-6123
DOI	10.1016/bs.pbr.2022.04.010
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Article ; Online: Using light to tell the time of day: sensory coding in the mammalian circadian visual network.

Brown, Timothy M

The Journal of experimental biology

2016 Volume 219, Issue Pt 12, Page(s) 1779–1792

Abstract: Circadian clocks are a near-ubiquitous feature of biology, allowing organisms to optimise their physiology to make the most efficient use of resources and adjust behaviour to maximise survival over the solar day. To fulfil this role, circadian clocks ... ...

Abstract	Circadian clocks are a near-ubiquitous feature of biology, allowing organisms to optimise their physiology to make the most efficient use of resources and adjust behaviour to maximise survival over the solar day. To fulfil this role, circadian clocks require information about time in the external world. This is most reliably obtained by measuring the pronounced changes in illumination associated with the earth's rotation. In mammals, these changes are exclusively detected in the retina and are relayed by direct and indirect neural pathways to the master circadian clock in the hypothalamic suprachiasmatic nuclei. Recent work reveals a surprising level of complexity in this sensory control of the circadian system, including the participation of multiple photoreceptive pathways conveying distinct aspects of visual and/or time-of-day information. In this Review, I summarise these important recent advances, present hypotheses as to the functions and neural origins of these sensory signals, highlight key challenges for future research and discuss the implications of our current knowledge for animals and humans in the modern world.
MeSH term(s)	Animals ; Circadian Clocks ; Hypothalamus/physiology ; Light ; Mammals/physiology ; Retina/physiology ; Suprachiasmatic Nucleus/physiology
Language	English
Publishing date	2016-06-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	218085-6
ISSN	1477-9145 ; 0022-0949
ISSN (online)	1477-9145
ISSN	0022-0949
DOI	10.1242/jeb.132167
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Article ; Online: A Bright Idea for Improving Spatial Memory.

Milosavljevic, Nina / Brown, Timothy M / Lucas, Robert J

Neuron

2021 Volume 109, Issue 2, Page(s) 197–199

Abstract: In this issue of Neuron, Huang et al. (2021) reveal a new influence of light on memory. They show that in mice, daily exposure to bright light over several weeks produces lasting increases in spatial memory and assign this effect to a circuit originating ...

Abstract	In this issue of Neuron, Huang et al. (2021) reveal a new influence of light on memory. They show that in mice, daily exposure to bright light over several weeks produces lasting increases in spatial memory and assign this effect to a circuit originating in the retina and encompassing the ventral lateral geniculate and reuniens nuclei.
MeSH term(s)	Animals ; Mice ; Midline Thalamic Nuclei ; Neurons ; Retina ; Spatial Memory
Language	English
Publishing date	2021-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2020.12.020
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Article: Colour and melanopsin mediated responses in the murine retina.

Mouland, Joshua W / Watson, Alex J / Martial, Franck P / Lucas, Robert J / Brown, Timothy M

Frontiers in cellular neuroscience

2023 Volume 17, Page(s) 1114634

Abstract: Introduction: ...

Abstract	Introduction:
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2023.1114634
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Article ; Online: Additive contributions of melanopsin and both cone types provide broadband sensitivity to mouse pupil control.

Hayter, Edward A / Brown, Timothy M

BMC biology

2018 Volume 16, Issue 1, Page(s) 83

Abstract: Background: Intrinsically photosensitive retinal ganglion cells (ipRGCs) drive an array of non-image-forming (NIF) visual responses including circadian photoentrainment and the pupil light reflex. ipRGCs integrate extrinsic (rod/cone) and intrinsic ( ... ...

Abstract	Background: Intrinsically photosensitive retinal ganglion cells (ipRGCs) drive an array of non-image-forming (NIF) visual responses including circadian photoentrainment and the pupil light reflex. ipRGCs integrate extrinsic (rod/cone) and intrinsic (melanopsin) photoreceptive signals, but the contribution of cones to ipRGC-dependent responses remains incompletely understood. Given recent data revealing that cone-derived colour signals influence mouse circadian timing and pupil responses in humans, here we set out to investigate the role of colour information in pupil control in mice. Results: We first recorded electrophysiological activity from the pretectal olivary nucleus (PON) of anaesthetised mice with a red-shifted cone population (Opn1mw Conclusion: Our data reveal a key difference in the sensory control of the mouse pupil relative to another major target of ipRGCs-the circadian clock. Whereas the latter uses colour information to help estimate time of day, the mouse pupil instead sums signals across cone opsin classes to provide broadband spectral sensitivity to changes in illumination. As such, while the widespread co-occurrence of chromatic responses and melanopsin input in the PON supports a close association between colour discrimination mechanisms and NIF visual processing, our data suggest that colour opponent PON cells in the mouse contribute to functions other than pupil control.
MeSH term(s)	Animals ; Color Vision/physiology ; Male ; Mice ; Photic Stimulation ; Pretectal Region/physiology ; Retinal Cone Photoreceptor Cells/physiology ; Rod Opsins/metabolism
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2018-07-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1741-7007
ISSN (online)	1741-7007
DOI	10.1186/s12915-018-0552-1
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Article ; Online: Suprachiasmatic nucleus-dependent and independent outputs driving rhythmic activity in hypothalamic and thalamic neurons.

Harding, Court / Bechtold, David A / Brown, Timothy M

BMC biology

2020 Volume 18, Issue 1, Page(s) 134

Abstract: Background: Daily variations in mammalian physiology are under control of a central clock in the suprachiasmatic nucleus (SCN). SCN timing signals are essential for coordinating cellular clocks and associated circadian variations in cell and tissue ... ...

Abstract	Background: Daily variations in mammalian physiology are under control of a central clock in the suprachiasmatic nucleus (SCN). SCN timing signals are essential for coordinating cellular clocks and associated circadian variations in cell and tissue function across the body; however, direct SCN projections primarily target a restricted set of hypothalamic and thalamic nuclei involved in physiological and behavioural control. The role of the SCN in driving rhythmic activity in these targets remains largely unclear. Here, we address this issue via multielectrode recording and manipulations of SCN output in adult mouse brain slices. Results: Electrical stimulation identifies cells across the midline hypothalamus and ventral thalamus that receive inhibitory input from the SCN and/or excitatory input from the retina. Optogenetic manipulations confirm that SCN outputs arise from both VIP and, more frequently, non-VIP expressing cells and that both SCN and retinal projections almost exclusively target GABAergic downstream neurons. The majority of midline hypothalamic and ventral thalamic neurons exhibit circadian variation in firing and those receiving inhibitory SCN projections consistently exhibit peak activity during epochs when SCN output is low. Physical removal of the SCN confirms that neuronal rhythms in ~ 20% of the recorded neurons rely on central clock input but also reveals many neurons that can express circadian variation in firing independent of any SCN input. Conclusions: We identify cell populations across the midline hypothalamus and ventral thalamus exhibiting SCN-dependent and independent rhythms in neural activity, providing new insight into the mechanisms by which the circadian system generates daily physiological rhythms.
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Hypothalamus/physiology ; Mice ; Neurons/physiology ; Suprachiasmatic Nucleus/physiology ; Thalamus/physiology
Language	English
Publishing date	2020-09-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1741-7007
ISSN (online)	1741-7007
DOI	10.1186/s12915-020-00871-8
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Article ; Online: Modulations in irradiance directed at melanopsin, but not cone photoreceptors, reliably alter electrophysiological activity in the suprachiasmatic nucleus and circadian behaviour in mice.

Mouland, Josh W / Martial, Franck P / Lucas, Robert J / Brown, Timothy M

Journal of pineal research

2021 Volume 70, Issue 4, Page(s) e12735

Abstract: Intrinsically photosensitive retinal ganglion cells convey intrinsic, melanopsin-based, photoreceptive signals alongside those produced by rods and cones to the suprachiasmatic nucleus (SCN) circadian clock. To date, experimental data suggest that ... ...

Abstract	Intrinsically photosensitive retinal ganglion cells convey intrinsic, melanopsin-based, photoreceptive signals alongside those produced by rods and cones to the suprachiasmatic nucleus (SCN) circadian clock. To date, experimental data suggest that melanopsin plays a more significant role in measuring ambient light intensity than cone photoreception. Such studies have overwhelmingly used diffuse light stimuli, whereas light intensity in the world around us varies across space and time. Here, we investigated the extent to which melanopsin or cone signals support circadian irradiance measurements in the presence of naturalistic spatiotemporal variations in light intensity. To address this, we first presented high- and low-contrast movies to anaesthetised mice whilst recording extracellular electrophysiological activity from the SCN. Using a mouse line with altered cone sensitivity (Opn1mw
MeSH term(s)	Animals ; Behavior, Animal/radiation effects ; Circadian Rhythm/physiology ; Circadian Rhythm/radiation effects ; Humans ; Light/adverse effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Retinal Cone Photoreceptor Cells/radiation effects ; Rod Opsins/radiation effects ; Suprachiasmatic Nucleus/physiology
Chemical Substances	Rod Opsins ; melanopsin
Language	English
Publishing date	2021-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	632697-3
ISSN	1600-079X ; 0742-3098
ISSN (online)	1600-079X
ISSN	0742-3098
DOI	10.1111/jpi.12735
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Article ; Online: Associations between light exposure and sleep timing and sleepiness while awake in a sample of UK adults in everyday life.

Didikoglu, Altug / Mohammadian, Navid / Johnson, Sheena / van Tongeren, Martie / Wright, Paul / Casson, Alexander J / Brown, Timothy M / Lucas, Robert J

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 42, Page(s) e2301608120

Abstract: Experimental and interventional studies show that light can regulate sleep timing and sleepiness while awake by setting the phase of circadian rhythms and supporting alertness. The extent to which differences in light exposure explain variations in sleep ...

Abstract	Experimental and interventional studies show that light can regulate sleep timing and sleepiness while awake by setting the phase of circadian rhythms and supporting alertness. The extent to which differences in light exposure explain variations in sleep and sleepiness within and between individuals in everyday life remains less clear. Here, we establish a method to address this deficit, incorporating an open-source wearable wrist-worn light logger (SpectraWear) and smartphone-based online data collection. We use it to simultaneously record longitudinal light exposure (in melanopic equivalent daylight illuminance), sleep timing, and subjective alertness over seven days in a convenience sample of 59 UK adults without externally imposed circadian challenge (e.g., shift work or jetlag). Participants reliably had strong daily rhythms in light exposure but frequently were exposed to less light during the daytime and more light in pre-bedtime and sleep episodes than recommended [T. M. Brown
MeSH term(s)	Adult ; Humans ; Wakefulness ; Sleepiness ; Sleep/physiology ; Circadian Rhythm/physiology ; United Kingdom ; Melatonin
Chemical Substances	Melatonin (JL5DK93RCL)
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2301608120
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Article ; Online: Acute In Vivo Multielectrode Recordings from the Mouse Suprachiasmatic Nucleus.

Mouland, Joshua / Walmsley, Lauren / Brown, Timothy M / Lucas, Robert J

Methods in molecular biology (Clifton, N.J.)

2020 Volume 2130, Page(s) 249–262

Abstract: The discovery of the suprachiasmatic nucleus (SCN) as the master mammalian pacemaker has since opened up a variety of alternative methods for assessing how external timing cues influence the clock. One powerful approach for understanding how sensory ... ...

Abstract	The discovery of the suprachiasmatic nucleus (SCN) as the master mammalian pacemaker has since opened up a variety of alternative methods for assessing how external timing cues influence the clock. One powerful approach for understanding how sensory inputs influence the SCN is to monitor acute changes in SCN electrophysiological activity via in vivo extracellular recording. This methodology offers the ability to monitor stimulus-evoked changes in SCN function at very fine timescales and to rapidly test multiple stimuli and/or stimulus repeats within a single animal. In this chapter we describe our methods for acute in vivo multielectrode recording in head-fixed, anesthetized rodents. These allow for monitoring of single-cell/population activity for >12 h; enable the delivery of carefully controlled sensory stimuli; can be used alongside an array of established or novel experimental tools; and are easily adapted to study activity in any other brain region.
MeSH term(s)	Animals ; Electroencephalography/instrumentation ; Electroencephalography/methods ; Evoked Potentials, Visual ; Mice ; Microelectrodes ; Photic Stimulation/methods ; Suprachiasmatic Nucleus/physiology
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0381-9_19
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