The Experts below are selected from a list of 3309 Experts worldwide ranked by ideXlab platform
Robert J Lucas - One of the best experts on this subject based on the ideXlab platform.
-
Form vision from Melanopsin in humans
Nature Communications, 2019Co-Authors: Annette E Allen, Franck P Martial, Robert J LucasAbstract: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 (
-
Melanopsin contributions to the representation of images in the early visual system
Current Biology, 2017Co-Authors: Annette E Allen, Riccardo Storchi, Franck P Martial, Robert Bedford, Robert J LucasAbstract:Summary 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 (
-
Melanopsin driven light adaptation in mouse vision
Current Biology, 2014Co-Authors: Annette E Allen, Riccardo Storchi, Franck P Martial, Timothy M Brown, Rasmus S Petersen, Marcelo A Montemurro, Robert J LucasAbstract:BACKGROUND: 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"). RESULTS: 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. CONCLUSIONS: 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.
-
Melanopsin-driven light adaptation in mouse vision.
Current Biology, 2014Co-Authors: Annette E Allen, Riccardo Storchi, Franck P Martial, Timothy M Brown, Rasmus S Petersen, Marcelo A Montemurro, Robert J LucasAbstract:Summary Background 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"). Results 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. Conclusions 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.
-
human Melanopsin forms a pigment maximally sensitive to blue light λmax 479 nm supporting activation of gq 11 and gi o signalling cascades
Proceedings of The Royal Society B: Biological Sciences, 2013Co-Authors: Helena J Bailes, Robert J LucasAbstract:A subset of mammalian retinal ganglion cells expresses an opsin photopigment (Melanopsin, Opn4) and is intrinsically photosensitive. The human retina contains Melanopsin, but the literature lacks a direct investigation of its spectral sensitivity or G-protein selectivity. Here, we address this deficit by studying physiological responses driven by human Melanopsin under heterologous expression in HEK293 cells. Luminescent reporters for common second messenger systems revealed that light induces a high amplitude increase in intracellular calcium and a modest reduction in cAMP in cells expressing human Melanopsin, implying that this pigment is able to drive responses via both Gq and Gi/o class G-proteins. Melanopsins from mouse and amphioxus had a similar profile of G-protein coupling in HEK293 cells, but chicken Opn4m and Opn4x pigments exhibited some Gs activity in addition to a strong Gq/11 response. An action spectrum for the calcium response in cells expressing human Melanopsin had the predicted form for an opsin : vitamin A1 pigment and peaked at 479 nm. The G-protein selectivity and spectral sensitivity of human Melanopsin is similar to that previously described for rodents, supporting the utility of such laboratory animals for developing methods of manipulating this system using light or pharmacological agents.
Samer Hattar - One of the best experts on this subject based on the ideXlab platform.
-
a role for Melanopsin in alpha retinal ganglion cells and contrast detection
Neuron, 2014Co-Authors: Tiffany M. Schmidt, Nazia M. Alam, Paulo Kofuji, Glen T. Prusky, Shan Chen, Wei Li, Samer HattarAbstract:Summary Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated Melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, Melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either Melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for Melanopsin and ipRGCs in vision. Video Abstract
-
identification of critical phosphorylation sites on the carboxy tail of Melanopsin
Biochemistry, 2014Co-Authors: Joseph R. Blasic, Samer Hattar, Evan G. Cameron, Devyani Ujla, Vanessa Matoscruz, Marnie E Halpern, Phyllis R. RobinsonAbstract:Light-activated opsins undergo carboxy-terminal phosphorylation, which contributes to the deactivation of their photoresponse. The photopigment Melanopsin possesses an unusually long carboxy tail containing 37 serine and threonine sites that are potential sites for phosphorylation by a G-protein dependent kinase (GRK). Here, we show that a small cluster of six to seven sites is sufficient for deactivation of light-activated mouse Melanopsin. Surprisingly, these sites are distinct from those that regulate deactivation of rhodopsin. In zebrafish, there are five different Melanopsin genes that encode proteins with distinct carboxy-terminal domains. Naturally occurring changes in the same cluster of phosphorylatable amino acids provides diversity in the deactivation kinetics of the zebrafish proteins. These results suggest that variation in phosphorylation sites provides flexibility in the duration and kinetics of Melanopsin-mediated light responses.
-
A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection
Neuron, 2014Co-Authors: Tiffany M. Schmidt, Nazia M. Alam, Paulo Kofuji, Glen T. Prusky, Shan Chen, Wei Li, Samer HattarAbstract:Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated Melanopsin-expressingintrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, Melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either Melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for Melanopsin and ipRGCs in vision. © 2014 Elsevier Inc.
-
Melanopsin dependent nonvisual responses evidence for photopigment bistability in vivo
Journal of Biological Rhythms, 2007Co-Authors: Ludovic S Mure, Samer Hattar, C Rieux, Howard M CooperAbstract:In mammals, nonvisual responses to light have been shown to involve intrinsically photosensitive retinal ganglion cells (ipRGC) that express Melanopsin and that are modulated by input from both rods and cones. Recent in vitro evidence suggests that Melanopsin possesses dual photosensory and photoisomerase functions, previously thought to be a unique feature of inver- tebrate rhabdomeric photopigments. In cultured cells that normally do not respond to light, heterologous expression of mammalian Melanopsin confers light sensitivity that can be restored by prior stimulation with appropriate wavelengths. Using three different physiological and behavioral assays, we show that this in vitro property translates to in vivo, Melanopsin-dependent nonvisual responses. We find that prestimulation with long-wavelength light not only restores but enhances single-unit responses of SCN neurons to 480-nm light, whereas the long-wavelength stimulus alone fails to elicit any response. Recordings in Opn4 -/- mice confirm that Melanopsin provides the main photo- sensory input to the SCN, and furthermore, demonstrate that Melanopsin is required for response enhancement, because this capacity is abolished in the knockout mouse. The efficiency of the light-enhancement effect depends on wavelength, irradiance, and duration. Prior long-wavelength light exposure also enhances short-wavelength-induced phase shifts of locomotor activity and pupillary constriction, consistent with the expression of a photoisomerase- like function in nonvisual responses to light.
-
intrinsically photosensitive retinal ganglion cells detect light with a vitamin a based photopigment Melanopsin
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Yingbin Fu, Samer Hattar, Hsi Wen Liao, Haining Zhong, Min Hua H Wang, Hidetaka Maeda, Laura J FrishmanAbstract:In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual functions such as pupillary light reflex (PLR) and circadian photoentrainment. This photosensitivity requires Melanopsin, an invertebrate opsin-like protein expressed by the ipRGCs. The precise role of Melanopsin remains uncertain. One suggestion has been that Melanopsin may be a photoisomerase, serving to regenerate an unidentified pigment in ipRGCs. This possibility was echoed by a recent report that Melanopsin is expressed also in the mouse retinal pigment epithelium (RPE), a key center for regeneration of rod and cone pigments. To address this question, we studied mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments. Rpe65-/- ipRGCs were ≈20- to 40-fold less photosensitive than normal at both single-cell and behavioral (PLR) levels but were rescued by exogenous 9-cis-retinal (an 11-cis-retinal analog), indicating the requirement of a vitamin A-based chromophore for ipRGC photosensitivity. In contrast, 9-cis-retinal was unable to restore intrinsic photosensitivity to Melanopsin-ablated ipRGCs, arguing against Melanopsin functioning merely in photopigment regeneration. Interestingly, exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65-/- ipRGCs, suggesting that Melanopsin could be a bistable pigment. Finally, we detected no Melanopsin in the RPE and no changes in rod and cone sensitivities due to Melanopsin ablation. Together, these results strongly suggest that Melanopsin is the photopigment in the ipRGCs.
Galen E. Pickard - One of the best experts on this subject based on the ideXlab platform.
-
Melanopsin and non-Melanopsin expressing retinal ganglion cells innervate the hypothalamic suprachiasmatic nucleus
Visual Neuroscience, 2020Co-Authors: Patricia J Sollars, Ignacio Provencio, Cynthia A Smeraski, Jessica D. Kaufman, Malcolm D. Ogilvie, Galen E. PickardAbstract:Retinal input to the hypothalamic suprachiasmatic nucleus (SCN) synchronizes the SCN circadian oscillator to the external day/night cycle. Retinal ganglion cells that innervate the SCN via the retinohypothalamic tract are intrinsically light sensitive and express Melanopsin. In this study, we provide data indicating that not all SCN-projecting retinal ganglion cells express Melanopsin. To determine the proportion of ganglion cells afferent to the SCN that express Melanopsin, ganglion cells were labeled following transsynaptic retrograde transport of a recombinant of the Bartha strain of pseudorabies virus (PRV152) constructed to express the enhanced green fluorescent protein (EGFP). PRV152 injected into the anterior chamber of the eye retrogradely infects four retinorecipient nuclei in the brain via autonomic circuits to the eye, resulting in transneuronally labeled ganglion cells in the contralateral retina 96 h after intraocular infection. In animals with large bilateral lesions of the lateral geniculate body/optic tract, ganglion cells labeled with PRV152 are retrogradely infected from only the SCN. In these animals, most PRV152-infected ganglion cells were immunoreactive for Melanopsin. However, a significant percentage (10–20%) of EGFP-labeled ganglion cells did not express Melanopsin. These data suggest that in addition to the intrinsically light-sensitive Melanopsin-expressing ganglion cells, conventional ganglion cells also innervate the SCN. Thus, it appears that the rod/cone system of photoreceptors may provide signals to the SCN circadian system independent of intrinsically light-sensitive Melanopsin ganglion cells.
-
two types of Melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus
European Journal of Neuroscience, 2008Co-Authors: Scott B. Baver, Patricia J Sollars, Galen E. PickardAbstract:Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN) and the olivary pretectal nucleus (OPN), providing irradiance information for entrainment of circadian rhythms and for stimulating the pupillary light reflex. In this study, mice were used in which the Melanopsin gene was replaced with the tau-lacZgene. Heterozygous (tau-lacZ +/- ) mice express both Melanopsin and p-galactosidase. In tau-lacZ +/- mice, only ∼50% of Melanopsin ipRGCs contain p-galactosidase, and these cells are specifically labeled with a C-terminus Melanopsin antibody. Retrograde tracer injection into the SCN labels β-galactosidase-expressing ipRGCs (termed M1) that comprise ∼80% of the SCN-projecting ipRGCs. Ml ipRGCs and an additional set of ipRGCs (termed M2) are labeled with a Melanopsin antiserum targeted against the N-terminus of the Melanopsin protein; M2 ipRGCs do not contain detectable β-galactosidase, and these cells make up the remainder of the SCN-projecting RGCs. Tracer injection into the OPN labeled non-Melanopsin RGCs and both types of Melanopsin ipRGC: 45% M1 and 55% M2. Infection of the iris with pseudorabies virus (PRV) results in retrograde transneuronal label of OPN projection neurons that innervate preganglionic parasympathetic neurons of the Edinger-Westphal nucleus; PRV-labeled cells were located almost exclusively within the terminal field of M1 ipRGCs in the periphery (shell) of the OPN. The OPN core receives retinal input, and we hypothesize that the OPN core receives input from the M2 ipRGCs. Two subtypes of Melanopsin ipRGCs project differentially to the SCN and OPN; the functional significance of ipRGCs subtypes is currently unknown.
-
Two types of Melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus
European Journal of Neuroscience, 2008Co-Authors: Scott B. Baver, Galen E. Pickard, Patricia J SollarsAbstract:Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN) and the olivary pretectal nucleus (OPN), providing irradiance information for entrainment of circadian rhythms and for stimulating the pupillary light reflex. In this study, mice were used in which the Melanopsin gene was replaced with the tau-lacZ gene. Heterozygous (tau-lacZ+/-) mice express both Melanopsin and beta-galactosidase. In tau-lacZ+/- mice, only approximately 50% of Melanopsin ipRGCs contain beta-galactosidase, and these cells are specifically labeled with a C-terminus Melanopsin antibody. Retrograde tracer injection into the SCN labels beta-galactosidase-expressing ipRGCs (termed M1) that comprise approximately 80% of the SCN-projecting ipRGCs. M1 ipRGCs and an additional set of ipRGCs (termed M2) are labeled with a Melanopsin antiserum targeted against the N-terminus of the Melanopsin protein; M2 ipRGCs do not contain detectable beta-galactosidase, and these cells make up the remainder of the SCN-projecting RGCs. Tracer injection into the OPN labeled non-Melanopsin RGCs and both types of Melanopsin ipRGC: 45% M1 and 55% M2. Infection of the iris with pseudorabies virus (PRV) results in retrograde transneuronal label of OPN projection neurons that innervate preganglionic parasympathetic neurons of the Edinger-Westphal nucleus; PRV-labeled cells were located almost exclusively within the terminal field of M1 ipRGCs in the periphery (shell) of the OPN. The OPN core receives retinal input, and we hypothesize that the OPN core receives input from the M2 ipRGCs. Two subtypes of Melanopsin ipRGCs project differentially to the SCN and OPN; the functional significance of ipRGCs subtypes is currently unknown.
-
Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses
The Journal of Comparative Neurology, 2003Co-Authors: Patricia J Sollars, Ignacio Provencio, Michael Belenky, Cynthia A Smeraski, Galen E. PickardAbstract:Melanopsin is a novel opsin synthesized in a small subset of retinal ganglion cells. Ganglion cells expressing Melanopsin are capable of depolarizing in response to light in the absence of rod or cone input and are thus intrinsically light sensitive. Melanopsin ganglion cells convey information regarding general levels of environmental illumination to the suprachiasmatic nucleus, the intergeniculate leaflet, and the pretectum. Typically, retinal ganglion cells communicate information to central visual structures by receiving input from retinal photoreceptors via bipolar and amacrine cells. Because Melanopsin ganglion cells do not require synaptic input to generate light-induced signals, these cells need not receive synapses from other neurons in the retina. In this study, we examined the ultrastructure of Melanopsin ganglion cells in the mouse retina to determine the type (if any) of synaptic input these cells receive. Melanopsin immunoreaction product was associated primarily with the plasma membrane of (1) perikarya in the ganglion cell layer, (2) dendritic processes in the inner plexiform layer (IPL), and (3) axons in the optic fiber layer. Melanopsin-immunoreactive dendrites in the inner (ON) region of the IPL were postsynaptic to bipolar and amacrine terminals, whereas Melanopsin dendrites stratifying in the outer (OFF) region of the IPL received only amacrine terminals. These observations suggested that rod and/or cone signals may be capable of modifying the intrinsic light response in Melanopsin-expressing retinal ganglion cells. J. Comp. Neurol. 460:380–393, 2003. © 2003 Wiley-Liss, Inc.
Jens Hannibal - One of the best experts on this subject based on the ideXlab platform.
-
Regulation of Melanopsin Expression
Chronobiology International, 2020Co-Authors: Jens HannibalAbstract:Circadian rhythms in mammals are adjusted daily to the environmental day/night cycle by photic input via the retinohypothalamic tract (RHT). Retinal ganglion cells (RGCs) of the RHT constitute a separate light‐detecting system in the mammalian retina used for irradiance detection and for transmission to the circadian system and other non‐imaging forming processes in the brain. The RGCs of the RHT are intrinsically photosensitive due to the expression of Melanopsin, an opsin‐like photopigment. This notion is based on anatomical and functional data and on studies of mice lacking Melanopsin. Furthermore, heterologous expression of Melanopsin in non‐neuronal mammalian cell lines was found sufficient to render these cells photosensitive. Even though solid evidence regarding the function of Melanopsin exists, little is known about the regulation of Melanopsin gene expression. Studies in albino Wistar rats showed that the expression of Melanopsin is diurnal at both the mRNA and protein levels. The diurnal change...
-
Melanopsin expressing human retinal ganglion cells subtypes distribution and intraretinal connectivity
The Journal of Comparative Neurology, 2017Co-Authors: Jens Hannibal, J Fahrenkrug, Steffen Heegaard, Anders Christiansen, Jens Folke KiilgaardAbstract:: Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment Melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of Melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human Melanopsin, confocal microscopy and 3D reconstruction of Melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human Melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of Melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 Melanopsin-ir (0.63-0.75% of the total number of RGCs). The Melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the Melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human Melanopsin-ir RGCs, which most likely are involved in different functions.
-
phosphorylation of rat Melanopsin at ser 381 and ser 398 by light dark and its importance for intrinsically photosensitive ganglion cells iprgcs cellular ca2 signaling
Journal of Biological Chemistry, 2014Co-Authors: J Fahrenkrug, Birgitte Falktoft, Birgitte Georg, Jens Hannibal, Sarah B Kristiansen, Thomas Kjaer KlausenAbstract:The G protein-coupled light-sensitive receptor Melanopsin is involved in non-image-forming light responses including circadian timing. The predicted secondary structure of Melanopsin indicates a long cytoplasmic tail with many potential phosphorylation sites. Using bioinformatics, we identified a number of amino acids with a high probability of being phosphorylated. We generated antibodies against Melanopsin phosphorylated at Ser-381 and Ser-398, respectively. The antibody specificity was verified by immunoblotting and immunohistochemical staining of HEK-293 cells expressing rat Melanopsin mutated in Ser-381 or Ser-398. Using the antibody recognizing phospho-Ser-381 Melanopsin, we demonstrated by immunoblotting and immunohistochemical staining in HEK-293 cells expressing rat Melanopsin that the receptor is phosphorylated in this position during the dark and dephosphorylated when light is turned on. On the contrary, we found that Melanopsin at Ser-398 was unphosphorylated in the dark and became phosphorylated after light stimulation. The light-induced changes in phosphorylation at both Ser-381 and Ser-398 were rapid and lasted throughout the 4-h experimental period. Furthermore, phosphorylation at Ser-381 and Ser-398 was independent of each other. The changes in phosphorylation were confirmed in vivo by immunohistochemical staining of rat retinas during light and dark. We further demonstrated that mutation of Ser-381 and Ser-398 in Melanopsin-expressing HEK-293 cells affected the light-induced Ca2+ response, which was significantly reduced as compared with wild type. Examining the light-evoked Ca2+ response in a Melanopsin Ser-381 plus Ser-398 double mutant provided evidence that the phosphorylation events were independent.
-
Differential expression of Melanopsin mRNA and protein in Brown Norwegian rats.
Experimental Eye Research, 2012Co-Authors: Jens Hannibal, Birgitte Georg, Jan FahrenkrugAbstract:Abstract Melanopsin is expressed in a subpopulation of retinal ganglion cells rendering these cells intrinsically photosensitive (ipRGCs). The ipRGCs are the primary RGCs mediating light entrainment of the circadian clock and control of the pupillary light reflex, light regulated melatonin secretion and negative masking behaviour. Previous studies have demonstrated that Melanopsin expression in albino rats is regulated by light and darkness. The present study was undertaken to study the influence of light and darkness during the circadian day and after extended periods of constant light and darkness on Melanopsin expression in the pigmented retina of the Brown Norwegian rat ( Rattus norvegicus ). The diurnal and circadian expressions were examined in retinal extracts from rats euthanized every 4 h during a 24 h light/dark (LD) and a 24 h dark cycle (DD) using quantitative real-time PCR and Western blotting. To study whether light regulates Melanopsin expression, rats were sacrificed after being placed in either constant light (LL) or darkness for 3 or 21 d. Flat mount retinas from animals kept during either LL or DD were also examined by immunohistochemistry. Melanopsin mRNA expression displayed a significant rhythmic change during the LD cycle with peak expression around dusk and nadir at dawn. Melanopsin protein also changed over the LD cycle with peak expression at the end of the night and nadir at dusk. Rhythmic expression of Melanopsin mRNA but not Melanopsin protein was found in constant darkness. After 3 or 21 d in either LL or DD Melanopsin mRNA expression was unaltered. Melanopsin protein was at the same high level after 3 and 21 d in DD, whereas a significant decrease was found after prolonging the light period for 3 or 21 d. The change in Melanopsin protein was primarily due to change in immunoreactivity in the dendritic processes. In conclusion we found that light and darkness are important for regulation of Melanopsin protein expression whereas input from a retinal networks regulates Melanopsin mRNA expression. It is likely to speculate that altered level of Melanopsin is one way in which the retina adapts to environmental light and darkness conditions ensuring optimal light sensitivity for the transmission to the brain.
-
Melanopsin changes in neonatal albino rat independent of rods and cones
Neuroreport, 2007Co-Authors: Jens Hannibal, Birgitte Georg, J FahrenkrugAbstract:Intrinsically photosensitive retinal ganglion cells employ the photopigment Melanopsin and provide light information to brain areas responsible for the regulation ofcircadian rhythms.The expression of Melanopsin is regulated by environmental illumination, but it remains to be clarified whether the rods and cones are involved. Here, we examined the influence of 5 days of constant light and dark conditions on Melanopsin mRNA and protein expression in newborn albino rats, in which functional rods and cones have not yet been developed. We found that the Melanopsin mRNA level was unaffected, whereas the Melanopsin protein level was more than two-fold higher in the darkness-adapted group than in pups raised in constant light. In pups raised during 12:12h light/dark cycles, the Melanopsin protein level was significantly higher during the day than at night. Our findings indicate that Melanopsin protein changes are independent of input from the rods and cones.
Tiffany M. Schmidt - One of the best experts on this subject based on the ideXlab platform.
-
Melanopsin phototransduction is repurposed by iprgc subtypes to shape the function of distinct visual circuits
Neuron, 2018Co-Authors: Takuma Sonoda, Lutz Birnbaumer, Tiffany M. SchmidtAbstract:Summary Melanopsin is expressed in distinct types of intrinsically photosensitive retinal ganglion cells (ipRGCs), which drive behaviors from circadian photoentrainment to contrast detection. A major unanswered question is how the same photopigment, Melanopsin, influences such vastly different functions. Here we show that Melanopsin's role in contrast detection begins in the retina, via direct effects on M4 ipRGC (ON alpha RGC) signaling. This influence persists across an unexpectedly wide range of environmental light levels ranging from starlight to sunlight, which considerably expands the functional reach of Melanopsin on visual processing. Moreover, Melanopsin increases the excitability of M4 ipRGCs via closure of potassium leak channels, a previously unidentified target of the Melanopsin phototransduction cascade. Strikingly, this mechanism is selective for image-forming circuits, as M1 ipRGCs (involved in non-image forming behaviors), exhibit a Melanopsin-mediated decrease in excitability. Thus, Melanopsin signaling is repurposed by ipRGC subtypes to shape distinct visual behaviors.
-
loss of gq 11 genes does not abolish Melanopsin phototransduction
PLOS ONE, 2014Co-Authors: Kylie S Chew, Tiffany M. Schmidt, Paulo Kofuji, Alan C Rupp, Jeffrey M TrimarchiAbstract:In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment Melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity. Several studies of Melanopsin phototransduction have implicated a G-protein of the Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in Melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene involved in this process has remained elusive. Additionally, whether Gq/11 G-proteins are necessary for Melanopsin phototransduction in vivo has not yet been examined. We show here that the majority of ipRGCs express both Gna11 and Gna14, but neither Gnaq nor Gna15. Animals lacking the Melanopsin protein have well-characterized deficits in the PLR and circadian behaviors, and we therefore examined these non-imaging forming visual functions in a variety of single and double mutants for Gq/11 family members. All Gq/11 mutant animals exhibited PLR and circadian behaviors indistinguishable from WT. In addition, we show persistence of ipRGC light-evoked responses in Gna11−/−; Gna14−/− retinas using multielectrode array recordings. These results demonstrate that Gq, G11, G14, or G15 alone or in combination are not necessary for Melanopsin-based phototransduction, and suggest that ipRGCs may be able to utilize a Gq/11-independent phototransduction cascade in vivo.
-
Loss of gq/11 genes does not abolish Melanopsin phototransduction.
PLOS ONE, 2014Co-Authors: Kylie S Chew, Tiffany M. Schmidt, Paulo Kofuji, Alan C Rupp, Jeffrey M TrimarchiAbstract:In mammals, a subset of retinal ganglion cells (RGCs) expresses the photopigment Melanopsin, which renders them intrinsically photosensitive (ipRGCs). These ipRGCs mediate various non-image-forming visual functions such as circadian photoentrainment and the pupillary light reflex (PLR). Melanopsin phototransduction begins with activation of a heterotrimeric G protein of unknown identity. Several studies of Melanopsin phototransduction have implicated a G-protein of the Gq/11 family, which consists of Gna11, Gna14, Gnaq and Gna15, in Melanopsin-evoked depolarization. However, the exact identity of the Gq/11 gene involved in this process has remained elusive. Additionally, whether Gq/11 G-proteins are necessary for Melanopsin phototransduction in vivo has not yet been examined. We show here that the majority of ipRGCs express both Gna11 and Gna14, but neither Gnaq nor Gna15. Animals lacking the Melanopsin protein have well-characterized deficits in the PLR and circadian behaviors, and we therefore examined these non-imaging forming visual functions in a variety of single and double mutants for Gq/11 family members. All Gq/11 mutant animals exhibited PLR and circadian behaviors indistinguishable from WT. In addition, we show persistence of ipRGC light-evoked responses in Gna11−/−; Gna14−/− retinas using multielectrode array recordings. These results demonstrate that Gq, G11, G14, or G15 alone or in combination are not necessary for Melanopsin-based phototransduction, and suggest that ipRGCs may be able to utilize a Gq/11-independent phototransduction cascade in vivo.
-
a role for Melanopsin in alpha retinal ganglion cells and contrast detection
Neuron, 2014Co-Authors: Tiffany M. Schmidt, Nazia M. Alam, Paulo Kofuji, Glen T. Prusky, Shan Chen, Wei Li, Samer HattarAbstract:Summary Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated Melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, Melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either Melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for Melanopsin and ipRGCs in vision. Video Abstract
-
A Role for Melanopsin in Alpha Retinal Ganglion Cells and Contrast Detection
Neuron, 2014Co-Authors: Tiffany M. Schmidt, Nazia M. Alam, Paulo Kofuji, Glen T. Prusky, Shan Chen, Wei Li, Samer HattarAbstract:Distinct subclasses of retinal ganglion cells (RGCs) mediate vision and nonimage-forming functions such as circadian photoentrainment. This distinction stems from studies that ablated Melanopsin-expressingintrinsically photosensitive RGCs (ipRGCs) and showed deficits in nonimage-forming behaviors, but not image vision. However, we show that the ON alpha RGC, a conventional RGC type, is intrinsically photosensitive in mammals. In addition to their classical response to fast changes in contrast through rod/cone signaling, Melanopsin expression allows ON alpha RGCs to signal prior light exposure and environmental luminance over long periods of time. Consistent with the high contrast sensitivity of ON alpha RGCs, mice lacking either Melanopsin or ON alpha RGCs have behavioral deficits in contrast sensitivity. These findings indicate a surprising role for Melanopsin and ipRGCs in vision. © 2014 Elsevier Inc.