A Wrist-Worn Internet of Things Sensor Node for Wearable Equivalent Daylight Illuminance Monitoring.

Light exposure is a vital regulator of physiology and behavior in humans. However, monitoring of light exposure is not included in current wearable Internet of Things (IoT) devices, and only recently have international standards defined [Formula: see text] -optic equivalent daylight illuminance (EDI) measures for how the eye responds to light. This article reports a wearable light sensor node that can be incorporated into the IoT to provide monitoring of EDI exposure in real-world settings. We present the system design, electronic performance testing, and accuracy of EDI measurements when compared to a calibrated spectral source. This includes consideration of the directional response of the sensor, and a comparison of performance when placed on different parts of the body, and a demonstration of practical use over 7 days. Our device operates for 3.5 days between charges, with a sampling period of 30 s. It has 10 channels of measurement, over the range 415-910 nm, balancing accuracy and cost considerations. Measured [Formula: see text]-opic EDI results for 13 devices show a mean absolute error of less than 0.07 log lx, and a minimum between device correlation of 0.99. These findings demonstrate that accurate light sensing is feasible, including at wrist worn locations. We provide an experimental platform for use in future investigations in real-world light exposure monitoring and IoT-based lighting control.

Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research.

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.

Associations between light exposure and sleep timing and sleepiness while awake in a sample of UK adults in everyday life.

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 et al., PLoS Biol. 20, e3001571 (2022)]. Prior light exposure over several hours was associated with lower subjective sleepiness with, in particular, brighter light in the late sleep episode and after wake linked to reduced early morning sleepiness (sleep inertia). Higher pre-bedtime light exposure was associated with longer sleep onset latency. Early sleep timing was correlated with more reproducible and robust daily patterns of light exposure and higher daytime/lower night-time light exposure. Our study establishes a method for collecting longitudinal sleep and health/performance data in everyday life and provides evidence of associations between light exposure and important determinants of sleep health and performance.

Colour and melanopsin mediated responses in the murine retina.

Introduction: Intrinsically photosensitive retinal ganglion cells (ipRGCs) integrate melanopsin and rod/cone-mediated inputs to signal to the brain. Whilst originally identified as a cell type specialised for encoding ambient illumination, several lines of evidence indicate a strong association between colour discrimination and ipRGC-driven responses. Thus, cone-mediated colour opponent responses have been widely found across ipRGC target regions in the mouse brain and influence a key ipRGC-dependent function, circadian photoentrainment. Although ipRGCs exhibiting spectrally opponent responses have also been identified, the prevalence of such properties have not been systematically evaluated across the mouse retina or yet been found in ipRGC subtypes known to influence the circadian system. Indeed, there is still uncertainty around the overall prevalence of cone-dependent colour opponency across the mouse retina, given the strong retinal gradient in S and M-cone opsin (co)-expression and overlapping spectral sensitivities of most mouse opsins. Methods: To address this, we use photoreceptor isolating stimuli in multielectrode recordings from human red cone opsin knock-in mouse (Opn1mwR) retinas to systematically survey cone mediated responses and the occurrence of colour opponency across ganglion cell layer (GCL) neurons and identify ipRGCs based on spectral comparisons and/or the persistence of light responses under synaptic blockade. Results: Despite detecting robust cone-mediated responses across the retina, we find cone opponency is rare, especially outside of the central retina (overall ~3% of GCL neurons). In keeping with previous suggestions we also see some evidence of rod-cone opponency (albeit even more rare under our experimental conditions), but find no evidence for any enrichment of cone (or rod) opponent responses among functionally identified ipRGCs. Conclusion: In summary, these data suggest the widespread appearance of cone-opponency across the mouse early visual system and ipRGC-related responses may be an emergent feature of central visual processing mechanisms.

Brighter Time: A Smartphone App Recording Cognitive Task Performance and Illuminance in Everyday Life.

Light is an influential regulator of behavioural and physiological state in mammals. Features of cognitive performance such as memory, vigilance and alertness can be altered by bright light exposure under laboratory and field conditions. However, the importance of light as a regulator of performance in everyday life is hard to assess and has so far remained largely unclear. We set out to address this uncertainty by developing a tool to capture measures of cognitive performance and light exposure, at scale, and during everyday life. To this end, we generated an app (Brighter Time) which incorporated a psychomotor vigilance (PVT), an N-back and a visual search task with questionnaire-based assessments of demographic characteristics, general health, chronotype and sleep. The app also measured illuminance during task completion using the smartphone's intrinsic light meter. We undertook a pilot feasibility study of Brighter Time based on 91-week-long acquisition phases within a convenience sample (recruited by local advertisements and word of mouth) running Brighter Time on their own smartphones over two study phases in winter and summer. Study compliance was suitable (median = 20/21 requested task completions per subject). Statistically significant associations were observed between subjective sleepiness and performance in all tasks. Significant daily variations in PVT and visual search performance were also observed. Higher illuminance was associated with reduced reaction time and lower inverse efficiency score in the visual search. Brighter Time thus represents a viable option for large-scale collection of cognitive task data in everyday life, and is able to reveal associations between task performance and sleepiness, time of day and current illuminance. Brighter Time's utility could be extended to exploring associations with longer-term patterns of light exposure and/or other light metrics by integrating with wearable light meters.

Beyond irradiance: Visual signals influencing mammalian circadian function.

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.

Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults.

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.

Extensive cone-dependent spectral opponency within a discrete zone of the lateral geniculate nucleus supporting mouse color vision.

Color vision, originating with opponent processing of spectrally distinct photoreceptor signals, plays important roles in animal behavior.1-4 Surprisingly, however, comparatively little is understood about color processing in the brain, including in widely used laboratory mammals such as mice. The retinal gradient in S- and M-cone opsin (co-)expression has traditionally been considered an impediment to mouse color vision.5-8 However, recent data indicate that mice exhibit robust chromatic discrimination within the central-upper visual field.9 Retinal color opponency has been reported to emerge from superimposing inhibitory surround receptive fields on the cone opsin expression gradient, and by introducing opponent rod signals in retinal regions with sparse M-cone opsin expression.10-13 The relative importance of these proposed mechanisms in determining the properties of neurons at higher visual processing stages remains unknown. We address these questions using multielectrode recordings from the lateral geniculate nucleus (LGN) in mice with altered M-cone spectral sensitivity (Opn1mwR) and multispectral stimuli that allow selective modulation of signaling by individual opsin classes. Remarkably, we find many (∼25%) LGN cells are color opponent, that such cells are localized to a distinct medial LGN zone and that their properties cannot simply be explained by the proposed retinal opponent mechanisms. Opponent responses in LGN can be driven solely by cones, independent of cone-opsin expression gradients and rod input, with many cells exhibiting spatially congruent antagonistic receptive fields. Our data therefore suggest previously unidentified mechanisms may support extensive and sophisticated color processing in the mouse LGN.

Bright daytime light enhances circadian amplitude in a diurnal mammal.

Mammalian circadian rhythms are orchestrated by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN), which receives information about the 24 h light-dark cycle from the retina. The accepted function of this light signal is to reset circadian phase in order to ensure appropriate synchronization with the celestial day. Here, we ask whether light also impacts another key property of the circadian oscillation, its amplitude. To this end, we measured circadian rhythms in behavioral activity, body temperature, and SCN electrophysiological activity in the diurnal murid rodent Rhabdomys pumilio following stable entrainment to 12:12 light-dark cycles at four different daytime intensities (ranging from 18 to 1,900 lx melanopic equivalent daylight illuminance). R. pumilio showed strongly diurnal activity and body temperature rhythms in all conditions, but measures of rhythm robustness were positively correlated with daytime irradiance under both entrainment and subsequent free run. Whole-cell and extracellular recordings of electrophysiological activity in ex vivo SCN revealed substantial differences in electrophysiological activity between dim and bright light conditions. At lower daytime irradiance, daytime peaks in SCN spontaneous firing rate and membrane depolarization were substantially depressed, leading to an overall marked reduction in the amplitude of circadian rhythms in spontaneous activity. Our data reveal a previously unappreciated impact of daytime light intensity on SCN physiology and the amplitude of circadian rhythms and highlight the potential importance of daytime light exposure for circadian health.

Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia.

Electrical activity in the heart exhibits 24-hour rhythmicity, and potentially fatal arrhythmias are more likely to occur at specific times of day. Here, we demonstrate that circadian clocks within the brain and heart set daily rhythms in sinoatrial (SA) and atrioventricular (AV) node activity, and impose a time-of-day dependent susceptibility to ventricular arrhythmia. Critically, the balance of circadian inputs from the autonomic nervous system and cardiomyocyte clock to the SA and AV nodes differ, and this renders the cardiac conduction system sensitive to decoupling during abrupt shifts in behavioural routine and sleep-wake timing. Our findings reveal a functional segregation of circadian control across the heart's conduction system and inherent susceptibility to arrhythmia.

Modulations in irradiance directed at melanopsin, but not cone photoreceptors, reliably alter electrophysiological activity in the suprachiasmatic nucleus and circadian behaviour in mice.

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 (Opn1mwR mice) and multispectral light sources we then selectively varied irradiance of the movies for specific photoreceptor classes. We found that steps in melanopic irradiance largely account for the light induced-changes in SCN activity over a range of starting light intensities and in the presence of spatiotemporal modulation. By contrast, cone-directed changes in irradiance only influenced SCN activity when spatiotemporal contrast was low. Consistent with these findings, under housing conditions where we could independently adjust irradiance for melanopsin versus cones, the period lengthening effects of constant light on circadian rhythms in behaviour were reliably determined by melanopic irradiance, regardless of irradiance for cones. These data add to the growing evidence that modulating effective irradiance for melanopsin is an effective strategy for controlling the circadian impact of light.

A Bright Idea for Improving Spatial Memory.

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.

S-cone contribution to the acute melatonin suppression response in humans.

Light influences diverse aspects of human physiology and behaviour including neuroendocrine function, the circadian system and sleep. A role for melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) in driving such effects is well established. However, rod and/or cone signals routed through ipRGCs could also influence "non-visual" spectral sensitivity. In humans, this has been most extensively studied for acute, light-dependent, suppression of nocturnal melatonin production. Of the published action spectra for melatonin suppression, one demonstrates a spectral sensitivity consistent with that expected for melanopsin while our own (using briefer 30 minute light exposures) displays very high sensitivity to short wavelength light, suggesting a contribution of S-cones. To clarify that possibility, six healthy young male participants were each exposed to 30 minutes of five irradiances of 415 nm monochromatic light (1-40 µW/cm2 ) across different nights. These data were then combined with the original action spectrum. The aggregated data are incompatible with the involvement of any single-opsin and multi-opsin models based on the original action spectrum (including Circadian Stimulus) fail to predict the responses to 415 nm stimuli. Instead, the extended action spectrum can be most simply approximated by an ~2:1 combination of melanopsin and S-cone signals. Such a model also better describes the magnitude of melatonin suppression observed in other studies using an equivalent 30 minute mono- or polychromatic light paradigm but not those using longer (90 minute) light exposures. In sum, these data provide evidence for an initial S-cone contribution to melatonin suppression that rapidly decays under extended light exposure.

Acute In Vivo Multielectrode Recordings from the Mouse Suprachiasmatic Nucleus.

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.

Suprachiasmatic nucleus-dependent and independent outputs driving rhythmic activity in hypothalamic and thalamic neurons.

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.

Very regular high-frequency pulsation modes in young intermediate-mass stars.

Asteroseismology probes the internal structures of stars by using their natural pulsation frequencies1. It relies on identifying sequences of pulsation modes that can be compared with theoretical models, which has been done successfully for many classes of pulsators, including low-mass solar-type stars2, red giants3, high-mass stars4 and white dwarfs5. However, a large group of pulsating stars of intermediate mass-the so-called δ Scuti stars-have rich pulsation spectra for which systematic mode identification has not hitherto been possible6,7. This arises because only a seemingly random subset of possible modes are excited and because rapid rotation tends to spoil regular patterns8-10. Here we report the detection of remarkably regular sequences of high-frequency pulsation modes in 60 intermediate-mass main-sequence stars, which enables definitive mode identification. The space motions of some of these stars indicate that they are members of known associations of young stars, as confirmed by modelling of their pulsation spectra.

Spectral sensitivity of cone vision in the diurnal murid Rhabdomys pumilio.

An animal's temporal niche - the time of day at which it is active - is known to drive a variety of adaptations in the visual system. These include variations in the topography, spectral sensitivity and density of retinal photoreceptors, and changes in the eye's gross anatomy and spectral transmission characteristics. We have characterised visual spectral sensitivity in the murid rodent Rhabdomys pumilio (the four-striped grass mouse), which is in the same family as (nocturnal) mice and rats but exhibits a strong diurnal niche. As is common in diurnal species, the R. pumilio lens acts as a long-pass spectral filter, providing limited transmission of light <400 nm. Conversely, we found strong sequence homologies with the R. pumilio SWS and MWS opsins and those of related nocturnal species (mice and rats) whose SWS opsins are maximally sensitive in the near-UV. We continued to assess in vivo spectral sensitivity of cone vision using electroretinography and multi-channel recordings from the visual thalamus. These revealed that responses across the human visible range could be adequately described by those of a single pigment (assumed to be MWS opsin) maximally sensitive at ∼500 nm, but that sensitivity in the near-UV required inclusion of a second pigment whose peak sensitivity lay well into the UV range (λmax<400 nm, probably ∼360 nm). We therefore conclude that, despite the UV-filtering effects of the lens, R. pumilio retains an SWS pigment with a UV-A λmax In effect, this somewhat paradoxical combination of long-pass lens and UV-A λmax results in narrow-band sensitivity for SWS cone pathways in the UV-A range.

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

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.

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms.

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.