At intermediate (mesopic) light levels, rods and cones are both active and can contribute to vision. This presents a challenge to the retina because the visual responses originating with rods and ...cones are distinct, yet their visual responses must be seamlessly combined. The current study aimed to establish how the circadian clock regulates rod and/or cone vision in these conditions, given the strong time-of-day change in the reliance on each photoreceptor. Visual responses were recorded in the retina and visual thalamus of anaesthetized male mice at distinct circadian time points, and the method of receptor silent substitution was used to selectively stimulate different photoreceptor types. With stimuli designed to only activate rods, responses in the mesopic range were highly rhythmic and peaked in amplitude in the subjective night. This rhythm was abolished following intravitreal injection of the gap junction blocker meclofenamic acid, consistent with a circadian variation in the strength of electrical coupling of photoreceptors. In contrast, responses to stimuli designed to only activate cones were arrhythmic within the mesopic to photopic range when adapted to the background irradiance. The outcome was that combined rod-plus-cone responses showed a stable contrast-response relationship across mesopic-photopic backgrounds in the circadian day, whereas at night, responses were significantly amplified at lower light levels. These data support the idea that the circadian clock is a key regulator of vision, in this case defining the relative amplitude of rod/cone vision across the mesopic transition according to time of day.
Although the importance of circadian clocks in regulating vision has been long recognized, less is known about how the clock shapes vision in conditions where both rods and cones are active (mesopic conditions). Here, the novel approach of receptor silent substitution has been applied to trace rod and cone visual responses in mice across the circadian cycle and has identified pronounced rhythms in rod, but not cone, vision. This has the effect of boosting responses in dimmer backgrounds at night at the cost of impaired contrast-response stability across the mesopic to photopic range. Thus, the circadian clock drives anticipatory changes in the relative contribution of rods versus cones to vision, which match the prevailing visual environment.
Form vision from melanopsin in humans Allen, Annette E; Martial, Franck P; Lucas, Robert J
Nature communications,
05/2019, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Detection and discrimination of spatial patterns is thought to originate with photoreception by rods and cones. Here, we investigated whether the inner-retinal photoreceptor melanopsin could ...represent a third origin for form vision. We developed a 4-primary visual display capable of presenting patterns differing in contrast for melanopsin vs cones, and generated spectrally distinct stimuli that were indistinguishable for cones (metamers) but presented contrast for melanopsin. Healthy observers could detect sinusoidal gratings formed by these metamers when presented in the peripheral retina at low spatial (≤0.8 cpd) and temporal (≤0.45 Hz) frequencies, and Michelson contrasts ≥14% for melanopsin. Metameric gratings became invisible at lower light levels (<10
melanopsin photons cm
sr
s
) when rods are more active. The addition of metameric increases in melanopsin contrast altered appearance of greyscale representations of coarse gratings and a range of everyday images. These data identify melanopsin as a new potential origin for aspects of spatial vision in humans.
Photoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment ...melanopsin 1–4. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection 5–7, no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance—a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance 8–12. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors.
► Melanopsin photoreception can be selectively modulated in an intact retina ► Melanopsin supports brightness discrimination in retinal degenerate and intact mice ► Melanopsin activation induces brightness percepts in healthy humans
Melanopsin photoreception enhances retinal responses to variations in ambient light (irradiance) and drives non-image-forming visual reflexes such as circadian entrainment 1–6. Melanopsin signals ...also reach brain regions responsible for form vision 7–9, but melanopsin’s contribution, if any, to encoding visual images remains unclear. We addressed this deficit using principles of receptor silent substitution to present images in which visibility for melanopsin versus rods+cones was independently modulated, and we recorded evoked responses in the mouse dorsal lateral geniculate nucleus (dLGN; thalamic relay for cortical vision). Approximately 20% of dLGN units responded to patterns visible only to melanopsin, revealing that melanopsin signals alone can convey spatial information. Spatial receptive fields (RFs) mapped using melanopsin-isolating stimuli had ON centers with diameters ∼13°. Melanopsin and rod+cone responses differed in the temporal domain, and responses to slow changes in radiance (<0.9 Hz) and stationary images were deficient when stimuli were rendered invisible for melanopsin. We employed these data to devise and test a mathematical model of melanopsin’s involvement in form vision and applied it, along with further experimental recordings, to explore melanopsin signals under simulated active view of natural scenes. Our findings reveal that melanopsin enhances the thalamic representation of scenes containing local correlations in radiance, compensating for the high temporal frequency bias of cone vision and the negative correlation between magnitude and frequency for changes in direction of view. Together, these data reveal a distinct melanopsin contribution to encoding visual images, predicting that, under natural view, melanopsin augments the early visual system’s ability to encode patterns over moderate spatial scales.
•A five-primary display is used to define melanopsin’s contribution to form vision•Melanopsin extends the spatiotemporal range of the mouse early visual system•The representation of spatial patterns is deficient when melanopsin is not engaged•A linear model predicting melanopsin’s contribution to pattern vision is defined
Allen et al. probe the origins of form vision and show that the inner retinal photoreceptor, melanopsin, extends its spatiotemporal range. Melanopsin augments the representation of patterns whose spatial scale is larger than that of ongoing changes in direction of view.
Many retinal dystrophies result in photoreceptor loss, but the inner retinal neurons can survive, making them potentially amenable to emerging optogenetic therapies. Here, we show that ectopically ...expressed human rod opsin, driven by either a non-selective or ON-bipolar cell-specific promoter, can function outside native photoreceptors and restore visual function in a mouse model of advanced retinal degeneration. Electrophysiological recordings from retinal explants and the visual thalamus revealed changes in firing (increases and decreases) induced by simple light pulses, luminance increases, and naturalistic movies in treated mice. These responses could be elicited at light intensities within the physiological range and substantially below those required by other optogenetic strategies. Mice with rod opsin expression driven by the ON-bipolar specific promoter displayed behavioral responses to increases in luminance, flicker, coarse spatial patterns, and elements of a natural movie at levels of contrast and illuminance (≈50–100 lux) typical of natural indoor environments. These data reveal that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities. Given the inherent advantages in employing a human protein, the simplicity of this intervention, and the quality of vision restored, we suggest that rod opsin merits consideration as an optogenetic actuator for treating patients with advanced retinal degeneration.
•Ectopic human rod opsin restores visual functions in advanced retinal degeneration•Rod opsin has greater sensitivity than current optogenetic strategies•Rod opsin-treated animals respond to spatial stimuli, flicker, and natural scenes•As a human protein ordinarily found in retinal tissue, barriers to clinic are minimized
Cehajic-Kapetanovic at al. show that ectopically expressed human rod opsin restores vision in a mouse model of advanced retinal degeneration. The quality of the restored vision compares favorably, especially in terms of sensitivity, with alternative approaches, and using a native human protein reduces barriers to future clinical trials.
Melanopsin enhances image persistence Woelders, Tom; Allen, Annette E.; Lucas, Robert J.
Current biology,
12/2023, Letnik:
33, Številka:
23
Journal Article
Recenzirano
Odprti dostop
Contributions of the inner retinal photopigment melanopsin to human visual perception are incompletely understood. Here, we use a four-primary display to produce stimuli differing in melanopsin ...versus cone contrast in psychophysical paradigms in eight subjects with normal color vision. We address two predictions from electrophysiological recordings of the melanopsin system in non-human mammals: melanopsin influences color and/or supports image persistence under visual fixation. We first construct chromatic contrast sensitivity contours for stimuli differing in melanopsin excitation presented as a central annulus (10°) or peripheral (22.5°) spot. We find that although including melanopsin contrast produces modest changes in the average chromatic coordinates in both eccentricities, this occurs equally at low (0.5 Hz) and higher (3.75 Hz) temporal frequencies, arguing that it reflects divergence in cone spectral sensitivity in our participants from that captured in standardized cone fundamentals rather than a melanopsin contribution to color. We continue to ask whether the established ability of melanopsin to sustain firing of visual neurons under extended light exposure has a visual correlate, using the optical illusion of Troxler fading in which blurred spots in periphery disappear during visual fixation. We find that introducing additional melanopsin contrast (+28% Michelson contrast) to either bright or dark spots increases fading latency by 35% ± 8.8% and 41% ± 13.6%, respectively. Our data argue that the primary contribution of melanopsin to perception under these conditions is not to provide a color percept but rather to enhance persistence of low spatial frequency patterns during visual fixation.
•Melanopsin enhances image persistence for low spatiotemporal frequency patterns•The image persistence originates from melanopsin rather than ipRGC spectral opponency•Melanopsin provides no substantial color percept
Woelders et al. demonstrate that melanopsin enhances image persistence, especially for low spatiotemporal details. Their color-matching experiments, using high melanopsin contrast metamers at frequencies both within and surpassing melanopsin’s temporal sensitivity range, reveal that melanopsin does not provide a substantial color percept.
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
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).
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.
Abstract
Objectives
Artificial light sources such as visual display units (VDUs) elicit a range of subconscious and reflex light responses, including increases in alertness and suppression of pineal ...melatonin. Such responses employ dedicated retinal circuits encompassing melanopsin photoreceptors. Here, we aimed to determine whether this arrangement can be exploited to modulate the impact of VDUs on melatonin onset and alertness without altering visual appearance.
Methods
We generated a five-primary VDU capable of presenting metameric movies (matched for color and luminance) but varying in melanopic-irradiance. Healthy human participants (n = 11) were exposed to the VDU from 18:00 to 23:00 hours at high- or low-melanopic setting in a randomized cross-over design and measured salivary melatonin and self-reported sleepiness at 30-minute intervals.
Results
Our VDU presented a 3× adjustment in melanopic-irradiance for images matched photometrically for color and luminance. Participants reported no significant difference in visual appearance (color and glare) between conditions. During the time in which the VDU was viewed, self-reported sleepiness and salivary melatonin levels increased significantly, as would be expected in this phase of the diurnal cycle. The magnitude of the increase in both parameters was significantly enhanced when melanopic-irradiance was reduced.
Conclusions
Our data demonstrate that melatonin onset and self-reported sleepiness can be modulated independent of photometric parameters (color and luminance) under a commonly encountered light exposure scenario (evening use of a VDU). They provide the first demonstration that the impact of light on alertness and melatonin production can be controlled independently of visual experience, and establish a VDU capable of achieving this objective.
In bright light, mammals use a distinct photopigment (melanopsin) to measure irradiance for centrally mediated responses such as circadian entrainment. We aimed to determine whether the information ...generated by melanopsin is also used by the visual system as a signal for light adaptation. To this end, we compared retinal and thalamic responses to a range of artificial and natural visual stimuli presented using spectral compositions that either approximate the mouse’s experience of natural daylight (“daylight”) or are selectively depleted of wavelengths to which melanopsin is most sensitive (“mel-low”).
We found reproducible and reversible changes in the flash electroretinogram between daylight and mel-low. Simultaneous recording in the dorsal lateral geniculate nucleus (dLGN) revealed that these reflect changes in feature selectivity of visual circuits in both temporal and spatial dimensions. A substantial fraction of units preferred finer spatial patterns in the daylight condition, while the population of direction-sensitive units became tuned to faster motion. The dLGN contained a richer, more reliable encoding of natural scenes in the daylight condition. These effects were absent in mice lacking melanopsin.
The feature selectivity of many neurons in the mouse dLGN is adjusted according to a melanopsin-dependent measure of environmental brightness. These changes originate, at least in part, within the retina. Melanopsin performs a role analogous to a photographer’s light meter, providing an independent measure of irradiance that determines optimal setting for visual circuits.
•Adjustments in visual performance in daylight conditions are driven by melanopsin•Melanopsin adjusts visual feature selectivity in spatial and temporal dimensions•Melanopsin facilitates a richer and more reliable encoding of natural scenes
Allen et al. show that aspects of light adaptation rely on a measure of brightness provided by melanopsin, the retina’s most recently discovered photoreceptor. Recordings from the mouse thalamus show that melanopsin controls the types of visual features that excite single neurons, allowing a richer, more reliable representation of natural scenes.
Background light intensity (irradiance) substantially impacts the visual code in the early visual system at synaptic and single-neuron levels, but its influence on population activity is largely ...unexplored. We show that fast narrowband oscillations, an important feature of population activity, systematically increase in amplitude as a function of irradiance in both anesthetized and awake, freely moving mice and at the level of the retina and dorsal lateral geniculate nucleus (dLGN). Narrowband coherence increases with irradiance across large areas of the dLGN, but especially for neighboring units. The spectral sensitivity of these effects and their substantial reduction in melanopsin knockout animals indicate a contribution from inner retinal photoreceptors. At bright backgrounds, narrowband coherence allows pooling of single-unit responses to become a viable strategy for enhancing visual signals within its frequency range.
•Narrowband oscillation amplitude in retina and dLGN is largely defined by irradiance•At high irradiances, control of oscillations originates with melanopsin photoreception•Daylight irradiance monotonically increases narrowband coherence•Narrowband coherence amplifies visual responses within its frequency range
Storchi et al. find that daylight irradiance, through melanopsin, systematically modulates amplitude of narrowband oscillations in mouse retina and dLGN and boosts visual signaling.
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