Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.

Atopic dermatitis (AD) is a chronic, relapsing immunoinflammatory skin condition characterized by sensations such as pruritis, pain, and neuronal hypersensitivity. The mechanisms underlying these sensations are multifactorial and involve complex crosstalk among several cutaneous components. This review explores the role these components play in the pathophysiology of atopic dermatitis. In the skin intercellular spaces, sensory nerves interact with keratinocytes and immune cells via myriad mediators and receptors. These interactions generate action potentials that transmit pruritis and pain signals from the peripheral nervous system to the brain. Keratinocytes, the most abundant cell type in the epidermis, are key effector cells, triggering crosstalk with immune cells and sensory neurons to elicit pruritis, pain, and inflammation. Filaggrin expression by keratinocytes is reduced in atopic dermatitis, causing a weakened skin barrier and elevated skin pH. Fibroblasts are the main cell type in the dermis and, in atopic dermatitis, appear to reduce keratinocyte differentiation, further weakening the skin barrier. Fibroblasts and mast cells promote inflammation while dermal dendritic cells appear to attenuate inflammation. Inflammatory cytokines and chemokines play a major role in AD pathogenesis. Type 2 immune responses typically generate pruritis, and the type 1 and type 3 responses generate pain. Type 2 responses and increased skin pH contribute to barrier dysfunction and promote dysbiosis of the skin microbiome, causing the proliferation of Staphyloccocus aureus. In conclusion, understanding the dynamic interactions between cutaneous components in AD could drive the development of therapies to improve the quality of life for patients with AD.

Atopic dermatitis (AD) is predominantly characterized by intense itching, but concomitant skin pain is experienced by more than 40% of patients. Patients with AD display considerable somatosensory aberrations, including increased nerve sensitivity to itch stimuli (hyperknesis), perception of itch from innocuous stimuli (alloknesis), or perception of pain from innocuous stimuli (allodynia). This review summarizes the current understanding of the similarities and differences in the peripheral mechanisms underlying itch and pain in AD. These distinct yet reciprocal sensations share many similarities in the peripheral nervous system, including common mediators (such as serotonin, endothelin-1, IL-33, and thymic stromal lymphopoietin), receptors (such as members of the G protein-coupled receptor family and Toll-like receptors), and ion channels for signal transduction (such as certain members of the transient receptor potential [TRP] cation channels). Itch-responding neurons are also sensitive to pain stimuli. However, there are distinct differences between itch and pain signaling. For example, specific immune responses are associated with pain (type 1 and/or type 3 cytokines and certain chemokine C-C [CCL2, CCL5] and C-X-C [CXCL] motif ligands) and itch (type 2 cytokines, including IL-31, and periostin). The TRP melastatin channels TRPM2 and TRPM3 have a role in pain but no known role in itch. Activation of μ-opioid receptors is known to alleviate pain but exacerbate itch. Understanding the connection between itch and pain mechanisms may offer new insights into the treatment of chronic pain and itch in AD.

The mosquito\'s antenna represents its main olfactory appendage for detecting volatile chemical cues from the environment. Whole-mount fluorescence in situ hybridization of ionotropic receptors (IRs) expressed in the antennae reveals that the antenna might be divisible into proximal and distal functional domains. The number of IR-positive cells appear stereotyped within each antennal segment (flagellomere). Highly expressed odor-tuning IRs exhibit distinct co-localization patterns with the IR coreceptors Ir8a, Ir25a, and Ir76b that might predict their functional properties. Genetic knockin and in vivo functional imaging of IR41c-expressing neurons indicate both odor-induced activation and inhibition in response to select amine compounds. Targeted mutagenesis of IR41c does not abolish behavioral responses to the amine compounds. Our study provides a comprehensive map of IR-expressing neurons in the main olfactory appendage of mosquitoes. These findings show organizing principles of Anopheles IR-expressing neurons, which might underlie their functional contribution to the detection of behaviorally relevant odors.

The shape and relative size of an ocular lens affect the focal length of the eye, with consequences for visual acuity and sensitivity. Lenses are typically spherical in aquatic animals with camera-type eyes and axially flattened in terrestrial species to facilitate vision in optical media with different refractive indices. Frogs and toads (Amphibia: Anura) are ecologically diverse, with many species shifting from aquatic to terrestrial ecologies during metamorphosis. We quantified lens shape and relative size using 179 micro X-ray computed tomography scans of 126 biphasic anuran species and tested for correlations with life stage, environmental transitions, adult habits and adult activity patterns. Across broad phylogenetic diversity, tadpole lenses are more spherical than those of adults. Biphasic species with aquatic larvae and terrestrial adults typically undergo ontogenetic changes in lens shape, whereas species that remain aquatic as adults tend to retain more spherical lenses after metamorphosis. Further, adult lens shape is influenced by adult habit; notably, fossorial adults tend to retain spherical lenses following metamorphosis. Finally, lens size relative to eye size is smaller in aquatic and semiaquatic species than other adult ecologies. Our study demonstrates how ecology shapes visual systems, and the power of non-invasive imaging of museum specimens for studying sensory evolution.

Colour vision allows animals to use the information contained in the spectrum of light to control important behavioural decisions such as selection of habitats, food or mates. Among arthropods, the largest animal phylum, we find completely colour-blind species as well as species with up to 40 different opsin genes or more than 10 spectral types of photoreceptors, we find a large diversity of optical methods shaping spectral sensitivity, we find eyes with different colour vision systems looking into the dorsal and ventral hemisphere, and species in which males and females see the world in different colours. The behavioural use of colour vision shows an equally astonishing diversity. Only the neural mechanisms underlying this sensory ability seems surprisingly conserved-not only within the phylum, but even between arthropods and the other well-studied phylum, chordates. The papers in this special issue allow a glimpse into the colourful world of arthropod colour vision, and besides giving an overview this introduction highlights how much more research is needed to fill in the many missing pieces of this large puzzle. This article is part of the theme issue \'Understanding colour vision: molecular, physiological, neuronal and behavioural studies in arthropods\'.

Differences in morphology, ecology, and behavior through ontogeny can result in opposing selective pressures at different life stages. Most animals, however, transition through two or more distinct phenotypic phases, which is hypothesized to allow each life stage to adapt more freely to its ecological niche. How this applies to sensory systems, and in particular how sensory systems adapt across life stages at the molecular level, is not well understood. Here, we used whole-eye transcriptomes to investigate differences in gene expression between tadpole and juvenile southern leopard frogs (Lithobates sphenocephalus), which rely on vision in aquatic and terrestrial light environments, respectively. Because visual physiology changes with light levels, we also tested the effect of light and dark exposure.
We found 42% of genes were differentially expressed in the eyes of tadpoles versus juveniles and 5% for light/dark exposure. Analyses targeting a curated subset of visual genes revealed significant differential expression of genes that control aspects of visual function and development, including spectral sensitivity and lens composition. Finally, microspectrophotometry of photoreceptors confirmed shifts in spectral sensitivity predicted by the expression results, consistent with adaptation to distinct light environments.
Overall, we identified extensive expression-level differences in the eyes of tadpoles and juveniles related to observed morphological and physiological changes through metamorphosis and corresponding adaptive shifts to improve vision in the distinct aquatic and terrestrial light environments these frogs inhabit during their life cycle. More broadly, these results suggest that decoupling of gene expression can mediate the opposing selection pressures experienced by organisms with complex life cycles that inhabit different environmental conditions throughout ontogeny.

Drosophila melanogaster olfactory neurons have long been thought to express only one chemosensory receptor gene family. There are two main olfactory receptor gene families in Drosophila, the odorant receptors (ORs) and the ionotropic receptors (IRs). The dozens of odorant-binding receptors in each family require at least one co-receptor gene in order to function: Orco for ORs, and Ir25a, Ir8a, and Ir76b for IRs. Using a new genetic knock-in strategy, we targeted the four co-receptors representing the main chemosensory families in D. melanogaster (Orco, Ir8a, Ir76b, Ir25a). Co-receptor knock-in expression patterns were verified as accurate representations of endogenous expression. We find extensive overlap in expression among the different co-receptors. As defined by innervation into antennal lobe glomeruli, Ir25a is broadly expressed in 88% of all olfactory sensory neuron classes and is co-expressed in 82% of Orco+ neuron classes, including all neuron classes in the maxillary palp. Orco, Ir8a, and Ir76b expression patterns are also more expansive than previously assumed. Single sensillum recordings from Orco-expressing Ir25a mutant antennal and palpal neurons identify changes in olfactory responses. We also find co-expression of Orco and Ir25a in Drosophila sechellia and Anopheles coluzzii olfactory neurons. These results suggest that co-expression of chemosensory receptors is common in insect olfactory neurons. Together, our data present the first comprehensive map of chemosensory co-receptor expression and reveal their unexpected widespread co-expression in the fly olfactory system.

Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. With the recent resolution revolution in cryo-electron microscopy, these and other TRP channel subtypes are now yielding their secrets to detailed atomic analysis, which is beginning to reveal structural underpinnings of stimulus detection and gating, ion permeation, and allosteric mechanisms governing signal integration. These insights are providing a framework for designing and evaluating modality-specific pharmacological agents for treating sensory and other TRP channel-associated disorders.

Among major vertebrate groups, anurans (frogs and toads) are understudied with regard to their visual systems, and little is known about variation among species that differ in ecology. We sampled North American anurans representing diverse evolutionary and life histories that likely possess visual systems adapted to meet different ecological needs. Using standard molecular techniques, visual opsin genes, which encode the protein component of visual pigments, were obtained from anuran retinas. Additionally, we extracted the visual opsins from publicly available genome and transcriptome assemblies, further increasing the phylogenetic and ecological diversity of our dataset to 33 species in total. We found that anurans consistently express four visual opsin genes (RH1, LWS, SWS1, and SWS2, but not RH2) even though reported photoreceptor complements vary widely among species. The proteins encoded by these genes showed considerable sequence variation among species, including at sites known to shift the spectral sensitivity of visual pigments in other vertebrates and had conserved substitutions that may be related to dim-light adaptation. Using molecular evolutionary analyses of selection (dN/dS) we found significant evidence for positive selection at a subset of sites in the dim-light rod opsin gene RH1 and the long wavelength sensitive cone opsin LWS. The function of sites inferred to be under positive selection are largely unknown, but a few are likely to affect spectral sensitivity and other visual pigment functions based on proximity to previously identified sites in other vertebrates. We also found the first evidence of visual opsin duplication in an amphibian with the duplication of the LWS gene in the African bullfrog, which had distinct LWS copies on the sex chromosomes suggesting the possibility of sex-specific visual adaptation. Taken together, our results indicate that ecological factors, such as habitat and life history, as well as behavior, may be driving changes to anuran visual systems.