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The pupil is the eye's adjustable aperture. Fitzpatrick et al. find that visual contrast constricts the pupil, increasing contrast. 1 This process improves behavioral performance. Its retinal origin has unorthodox elements, like interneurons that make connections in unusual locales and photoreceptive ganglion cells., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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.)

Light regulates physiology, mood, and behavior through signals sent to the brain by intrinsically photosensitive retinal ganglion cells (ipRGCs). How primate ipRGCs sense light is unclear, as they are rare and challenging to target for electrophysiological recording. We developed a method of acute identification within the live, ex vivo retina. Using it, we found that ipRGCs of the macaque monkey are highly specialized to encode irradiance (the overall intensity of illumination) by blurring spatial, temporal, and chromatic features of the visual scene. We describe mechanisms at the molecular, cellular, and population scales that support irradiance encoding across orders-of-magnitude changes in light intensity. These mechanisms are conserved quantitatively across the ~70 million years of evolution that separate macaques from mice.

Melanopsin is a light-activated G protein coupled receptor that is expressed widely across phylogeny. In mammals, melanopsin is found in intrinsically photosensitive retinal ganglion cells (ipRGCs), which are especially important for "non-image" visual functions that include the regulation of circadian rhythms, sleep, and mood. Photochemical and electrophysiological experiments have provided evidence that melanopsin has at least two stable conformations and is thus multistable, unlike the monostable photopigments of the classic rod and cone photoreceptors. Estimates of melanopsin's properties vary, challenging efforts to understand how the molecule influences vision. This article seeks to reconcile disparate views of melanopsin and offer a practical guide to melanopsin's complexities.

The newborn mouse's retina senses light even before the eye opens, informing the developing brain of the visual world. Without this information, the brain forms fewer connections and the adult mouse learns sluggishly., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Immunoreactivity for calcium-/calmodulin-dependent protein kinase II (CaMKII) in the primate dorsal lateral geniculate nucleus (dLGN) has been attributed to geniculocortical relay neurons and has also been suggested to arise from terminals of retinal ganglion cells. Here, we combined immunostaining with single-cell injections to investigate the expression of CaMKII in retinal ganglion cells of three primate species: macaque (Macaca fascicularis, M. nemestrina), human, and marmoset (Callithrix jacchus). We found that in all species, about 2%-10% of the total ganglion cell population expressed CaMKII. In all species, CaMKII was expressed by multiple types of wide-field ganglion cell including large sparse, giant sparse (melanopsin-expressing), broad thorny, and narrow thorny cells. Three other ganglion cells types, namely, inner and outer stratifying maze cells in macaque and tufted cells in marmoset were also found. Double labeling experiments showed that CaMKII-expressing cells included inner and outer stratifying melanopsin cells. Nearly all CaMKII-expressing ganglion cell types identified here are known to project to the koniocellular layers of the dLGN as well as to the superior colliculus. The best characterized koniocellular projecting cell type-the small bistratified (blue ON/yellow OFF) cell-was, however, not CaMKII-positive in any species. Our results indicate that the pattern of CaMKII expression in retinal ganglion cells is largely conserved across different species of primate suggesting a common functional role. But the results also show that CaMKII is not a marker for all koniocellular projecting retinal ganglion cells., (© 2022 Wiley Periodicals LLC.)

Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against the transcription factor special AT-rich binding protein 1 (Satb1, a protein which is expressed by on-off direction-selective ganglion cells in mouse retina) to study Satb1 expression in the retina of marmosets (Callithrix jacchus), macaques (Macaca fascicularis), and humans. In all species, Satb1 was exclusively expressed in retinal ganglion cells. The Satb1 cells made up ∼2% of the ganglion cell population in the central retina of all species, rising to a maximum ∼7% in peripheral marmoset retina. Intracellular injections in marmoset and macaque retinas revealed that most Satb1 expressing ganglion cells are widefield ganglion cells. In marmoset, Satb1 cells have a densely branching dendritic tree and include broad and narrow thorny, recursive bistratified, and parasol cells, all of which show some costratification with the outer or inner cholinergic amacrine cells. The recursive bistratified cells showed the strongest costratification but did not show extensive cofasciculation as reported for on-off direction-selective ganglion cells in rabbit and rodent retinas. In macaque, Satb1 was not expressed in recursive bistratified cells, but in large sparsely branching cells. Our findings further support the idea that the expression of transcription factors in retinal ganglion cells is not conserved across Old World (human and macaque) and New World (marmoset) primates and provides a further step to link a molecular marker with specific cell types., (© 2021 Wiley Periodicals LLC.)

In this issue of Neuron, Shah et al. reveal that coding of visual space by the primate retina varies across individuals and sexes. A computational model provides insight into themes and variations of coding. Implications for sight restoration are explored., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The fovea is a neural specialization that endows humans and other primates with the sharpest vision among mammals. This performance originates in the foveal cones, which are extremely narrow and long to form a high-resolution pixel array. Puzzlingly, this form is predicted to impede electrical conduction to an extent that appears incompatible with vision. We observe the opposite: signal flow through even the longest cones (0.4-mm axons) is essentially lossless. Unlike in most neurons, amplification and impulse generation by voltage-gated channels are dispensable. Rather, sparse channel activity preserves intracellular current, which flows as if unobstructed by organelles. Despite these optimizations, signaling would degrade if cones were lengthier. Because cellular packing requires that cone elongation accompanies foveal expansion, this degradation helps explain why the fovea is a constant, miniscule size despite multiplicative changes in eye size through evolution. These observations reveal how biophysical mechanisms tailor form-function relationships for primate behavioral performance., Competing Interests: Declaration of Interests M.T.H.D. is affiliated with the Center for Brain Science (Harvard University), the Division of Sleep Medicine (Brigham and Women’s Hospital, Harvard Medical School), and the Broad Institute of MIT and Harvard. All authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The mammalian visual system encodes information over a remarkable breadth of spatiotemporal scales and light intensities. This performance originates with its complement of photoreceptors: the classic rods and cones, as well as the intrinsically photosensitive retinal ganglion cells (ipRGCs). IpRGCs capture light with a G-protein-coupled receptor called melanopsin, depolarize like photoreceptors of invertebrates such as Drosophila, discharge electrical spikes, and innervate dozens of brain areas to influence physiology, behavior, perception, and mood. Several visual responses rely on melanopsin to be sustained and maximal. Some require ipRGCs to occur at all. IpRGCs fulfill their roles using mechanisms that include an unusual conformation of the melanopsin protein, an extraordinarily slow phototransduction cascade, divisions of labor even among cells of a morphological type, and unorthodox configurations of circuitry. The study of ipRGCs has yielded insight into general topics that include photoreceptor evolution, cellular diversity, and the steps from biophysical mechanisms to behavior., (Copyright © 2019 Elsevier Inc. All rights reserved.)

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Animal photoreceptors divide into two fundamental classes, ciliary and rhabdomeric. Jiang and colleagues demonstrate that this boundary is disregarded by the intrinsically photosensitive retinal ganglion cells of mammals. These neurons draw from phototransduction mechanisms of both classes, enriching the signals that they produce to drive a diversity of visual functions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Environmental illumination spans many log units of intensity and is tracked for essential functions that include regulation of the circadian clock, arousal state, and hormone levels. Little is known about the neural representation of light intensity and how it covers the necessary range. This question became accessible with the discovery of mammalian photoreceptors that are required for intensity-driven functions, the M1 ipRGCs. The spike outputs of M1s are thought to uniformly track intensity over a wide range. We provide a different understanding: individual cells operate over a narrow range, but the population covers irradiances from moonlight to full daylight. The range of most M1s is limited by depolarization block, which is generally considered pathological but is produced intrinsically by these cells. The dynamics of block allow the population to code stimulus intensity with flexibility and efficiency. Moreover, although spikes are distorted by block, they are regularized during axonal propagation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Intrinsically photosensitive retinal ganglion cells of the M1 type encode environmental irradiance for functions that include circadian and pupillary regulation. Their distinct role, morphology, and molecular markers indicate that they are stereotyped circuit elements, but their physiological uniformity has not been investigated in a systematic fashion. We have profiled the biophysical parameters of mouse M1s and found that extreme variation is their hallmark. Most parameters span 1-3 log units, and the full range is evident in M1s that innervate brain regions serving divergent functions. Biophysical profiles differ among cells possessing similar morphology and between neighboring M1s recorded simultaneously. Variation in each parameter is largely independent of that in others, allowing for flexible individualization. Accordingly, a common stimulus drives heterogeneous spike outputs across cells. By contrast, a population of directionally selective retinal ganglion cells appeared physiologically uniform under similar conditions. Thus, M1s lack biophysical constancy and send diverse signals downstream., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)