Previous studies have shown that with the use of tinted lenses (or colored filters), individuals with red–green color vision deficiency (CVD) report an improvement in their performance on certain color vision tests. In this context, this study examines the effects of a digitally generated red-colored filter and identifies the mechanism mainly responsible for the changes in red–green CVD observers’ performance on a D-15 arrangement test performed using the filter. We simulate the red filter digitally with the spectral transmittance similar to that of the X-Chrom, which is a red-tinted lens. Fourteen red–green CVD subjects are subjected to the D-15 test on a computer monitor under four filter conditions, consisting of one condition without the filter and three conditions with the filter, corresponding to the opacity of the red filter. The results show that while the simulated red filter improves the performance of deutans to arrange the caps in the D-15 test, this is not the case for protans. In addition, considerations based on the human cone-contrast model enable us to identify that the improvement in deutan observers largely results from the increase in the luminance contrast between stimuli and a background. To summarize, the red filter simulated in this study induces different changes in the red–green CVD observer luminance contrast between the protan and deutan types, with the result that the performance of deuteranopes improves while that of protanopes deteriorates.

Preserving of vision is the main goal in vision research. The presented research evaluates the preservation of visual function in Royal College of Surgeon (RCS) rats using a depth perception test. Rats were placed on a stage with one side containing an illusory steep drop (“cliff”) and another side with a minimal drop (“table”). Latency of stage dismounting and the percentage of rats that set their first foot on the “cliff” side were determined. Nondystrophic Long–Evans (LE) rats were tested as control. Electroretinogram and histology analysis were used to determine retinal function and structure. Four-week-old RCS rats presented a significantly shorter mean latency to dismount the stage compared with 6-week-old rats (mean ± standard error, 13.7 ± 1.68 vs. 20.85 ± 6.5 s, P = 0.018). Longer latencies were recorded as rats aged, reaching 45.72 s in 15-week-old rats (P < 0.00001 compared with 4-week-old rats). All rats at the age of 4 weeks placed their first foot on the table side. By contrast, at the age of 8 weeks, 28.6% rats dismounted on the cliff side and at the age of 10 and 15 weeks, rats randomly dismounted the stage to either table or cliff side. LE rats dismounted the stage faster than 4-week-old RCS rats, but the difference was not statistically significant (7 ± 1.58 s, P = 0.057) and all LE rats dismounted on the table side. The latency to dismount the stage in RCS rats correlated with maximal electroretinogram b-wave under dark and light adaptation (Spearman’s rho test = −0.603 and −0.534, respectively, all P < 0.0001), outer nuclear layer thickness (Spearman’s rho test = −0.764, P = 0.002), and number of S- and M-cones (Spearman’s rho test = −0.763 [P = 0.002], and −0.733 [P = 0.004], respectively). The cliff avoidance test is an objective, quick, and readily available method for the determination of RCS rats’ visual function.

Variability in the electrophysiological properties of homotypic photoreceptors is widespread and is thought to facilitate functioning under disparate illumination conditions. Compound eyes of insects have three sources of variability: inter-individual, intra-individual, and intra-ommatidial, the latter two overlapping. Here, I explored the causes of variability in Periplaneta americana, a nocturnal insect characterized by highly variable photoreceptor responses. By recording from photoreceptors in dissociated ommatidia, including consecutive recordings from photoreceptors in the same ommatidium (SO), I studied the variability of six properties: whole-cell membrane capacitance (Cm), phototransduction latency, maximal conductance (Gmax) and the slope factor of the sustained Kv current, absolute sensitivity in dim light, and sustained light-induced current (LIC) amplitude in bright light. Coefficient of variation (CV) metrics were used to compare variances in four experimental groups: SO, same animal (SA), all data combined “full sample” (FS), and full sample of all SO recordings (FSSO). For the normally distributed parameters Cm, Gmax, slope factor, and latency, the highest CV values were found in FS and FSSO, intermediate in SA, and the lowest in SO. On average, SO variance accounted for 47% of the full-sample variance in these four parameters. Absolute sensitivity and LIC values were not normally distributed, and the differences in variability between SO and FS/FSSO groups were smaller than for the other four parameters. These results indicate two main sources of variability, intra-ommatidial and inter-individual. Inter-individual variability was investigated by exposing adult cockroaches to constant light or dark for several months. In both groups, the majority of CV measures for the six parameters decreased compared to control, indicating substantial contribution of phenotypic plasticity to inter-individual differences. Analysis of variability of resting potential and elementary voltage responses revealed that resting potential is mainly determined by the sustained Kv conductance, whereas voltage bump amplitude is mainly determined by current bump amplitude and Cm.

There are more than 30 distinct types of mammalian retinal ganglion cells, each sensitive to different features of the visual environment. In rabbit retina, they can be grouped into four classes according to their morphology and stratification of their dendrites in the inner plexiform layer (IPL). The goal of this study was to describe the synaptic inputs to one type of Class IV ganglion cell, the third member of the sparsely branched Class IV cells (SB3). One cell of this type was partially reconstructed in a retinal connectome developed using automated transmission electron microscopy (ATEM). It had slender, relatively straight dendrites that ramify in the sublamina a of the IPL. The dendrites of the SB3 cell were always postsynaptic in the IPL, supporting its identity as a ganglion cell. It received 29% of its input from bipolar cells, a value in the middle of the range for rabbit retinal ganglion cells studied previously. The SB3 cell typically received only one synapse per bipolar cell from multiple types of presumed OFF bipolar cells; reciprocal synapses from amacrine cells at the dyad synapses were infrequent. In a few instances, the bipolar cells presynaptic to the SB3 ganglion cell also provided input to an amacrine cell presynaptic to the ganglion cell. There was apparently no crossover inhibition from narrow-field ON amacrine cells. Most of the amacrine cell inputs were from axons and dendrites of GABAergic amacrine cells, likely providing inhibitory input from outside the classical receptive field.

At the first retinal synapse, horizontal cells (HCs) contact both photoreceptor terminals and bipolar cell dendrites, modulating information transfer between these two cell types to enhance spatial contrast and mediate color opponency. The synaptic mechanisms through which these modulations occur are still debated. The initial hypothesis of a GABAergic feedback from HCs to cones has been challenged by pharmacological inconsistencies. Surround antagonism has been demonstrated to occur via a modulation of cone calcium channels through ephaptic signaling and pH changes in the synaptic cleft. GABAergic transmission between HCs and cones has been reported in some lower vertebrates, like the turtle and tiger salamander. In these reports, it was revealed that GABA is released from HCs through reverse transport and target GABA receptors are located at the cone terminals. In mammalian retinas, there is growing evidence that HCs can release GABA through conventional vesicular transmission, acting both on autaptic GABA receptors and on receptors expressed at the dendritic tips of the bipolar cells. The presence of GABA receptors on mammalian cone terminals remains equivocal. Here, we looked specifically for functional GABA receptors in mouse photoreceptors by recording in the whole-cell or amphotericin/gramicidin-perforated patch clamp configurations. Cones could be differentiated from rods through morphological criteria. Local GABA applications evoked a Cl− current in cones but not in rods. It was blocked by the GABAA receptor antagonist bicuculline methiodide and unaffected by the GABAC receptor antagonist TPMPA [(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid]. The voltage dependency of the current amplitude was as expected from a direct action of GABA on cone pedicles but not from an indirect modulation of cone currents following the activation of the GABA receptors of HCs. This supports a direct role of GABA released from HCs in the control of cone activity in the mouse retina.

Inhibition shapes activity and signal processing in neural networks through numerous mechanisms mediated by many different cell types. Here, we examined how one type of GABAergic interneuron in the retina, the A17 amacrine cell, influences visual information processing. Our results suggest that A17s, which make reciprocal feedback inhibitory synapses onto rod bipolar cell (RBC) synaptic terminals, extend the luminance range over which RBC synapses compute temporal contrast and enhance the reliability of contrast signals over this range. Inhibition from other amacrine cells does not influence these computational features. Although A17-mediated feedback is mediated by both GABAA and GABAC receptors, the latter plays the primary role in extending the range of contrast computation. These results identify specific functions for an inhibitory interneuron subtype, as well as specific synaptic receptors, in a behaviorally relevant neural computation.

Photoreceptors have high energy demands and densely packed mitochondria through which light passes before phototransduction. Old world primates including humans have three cone photoreceptor types mediating color vision with short (S blue), medium (M green), and long (L red) wavelength sensitivities. However, S-cones are enigmatic. They comprise <10% of the total cone population, their responses saturate early, and they are susceptible in aging and disease. Here, we show that primate S-cones actually have few mitochondria and are fueled by glycolysis, not by mitochondrial respiration. Glycolysis has a limited ability to sustain activity, potentially explaining early S-cone saturation. Mitochondria act as optical filters showing reduced light transmission at 400–450 nm where S-cones are most sensitive (420 nm). This absorbance is likely to arise in a mitochondrial porphyrin that absorbs strongly in the Soret band. Hence, reducing mitochondria will improve S-cone sensitivity but result in increased glycolysis as an alternative energy source, potentially increasing diabetic vulnerability due to restricted glucose access. Further, glycolysis carries a price resulting in premature functional decline as seen in aged S-cones. Soret band absorption may also impact on mitochondrial rich M and L cones by reducing sensitivity at the lower end of their spectral sensitivity range resulting in increased differentiation from S-cone responses. These data add to the list of unique characteristic of S-cones and may also explain aspects of their vulnerability.

Contrast sensitivity functions reveal information about a subject’s overall visual ability and have been investigated in several species of nonhuman primates (NHPs) with experimentally induced amblyopia and glaucoma. However, there are no published studies comparing contrast sensitivity functions across these species of normal NHPs. The purpose of this investigation was to compare contrast sensitivity across these primates to determine whether they are similar. Ten normal humans and eight normal NHPs (Macaca fascicularis) took part in this project. Previously published data from Macaca mulatta and Macaca nemestrina were also compared. Threshold was operationally defined as two misses in a row for a descending method of limits. A similar paradigm was used for the humans except that the descending method of limits was combined with a spatial, two-alternative forced choice (2-AFC) technique. The contrast sensitivity functions were fit with a double exponential function. The averaged peak contrast sensitivity, peak spatial frequency, acuity, and area under the curve for the humans were 268.9, 3.40 cpd, 27.3 cpd, and 2345.4 and for the Macaca fascicularis were 99.2, 3.93 cpd, 26.1 cpd, and 980.9. A two-sample t-test indicated that the peak contrast sensitivities (P = 0.001) and areas under the curve (P = 0.010) were significantly different. The peak spatial frequencies (P = 0.150) and the extrapolated visual acuities (P = 0.763) were not different. The contrast sensitivities for the Macaca fascicularis, Macaca mulatta, and Macaca nemestrina were qualitatively and quantitatively similar. The contrast sensitivity functions for the NHPs had lower peak contrast sensitivities and areas under the curve than the humans. Even though different methods have been used to measure contrast sensitivity in different species of NHP, the functions are similar. The contrast sensitivity differences and similarities between humans and NHPs need to be considered when using NHPs to study human disease.

In primate retina, the calcium-binding protein calbindin is expressed by a variety of neurons including cones, bipolar cells, and amacrine cells but it is not known which type(s) of cell express calbindin in the ganglion cell layer. The present study aimed to identify calbindin-positive cell type(s) in the amacrine and ganglion cell layer of human and marmoset retina using immunohistochemical markers for ganglion cells (RBPMS and melanopsin) and cholinergic amacrine (ChAT) cells. Intracellular injections following immunolabeling was used to reveal the morphology of calbindin-positive cells. In human retina, calbindin-labeled cells in the ganglion cell layer were identified as inner and outer stratifying melanopsin-expressing ganglion cells, and ON ChAT (starburst amacrine) cells. In marmoset, calbindin immunoreactivity in the ganglion cell layer was absent from ganglion cells but present in ON ChAT cells. In the inner nuclear layer of human retina, calbindin was found in melanopsin-expressing displaced ganglion cells and in at least two populations of amacrine cells including about a quarter of the OFF ChAT cells. In marmoset, a very low proportion of OFF ChAT cells was calbindin-positive. These results suggest that in both species there may be two types of OFF ChAT cells. Consistent with previous studies, the ratio of ON to OFF ChAT cells was about 70 to 30 in human and 30 to 70 in marmoset. Our results show that there are species-related differences between different primates with respect to the expression of calbindin.

There are four cone morphologies in zebrafish, corresponding to UV (U), blue (B), green (G), and red (R)-sensing types; yet genetically, eight cone opsins are expressed. How eight opsins are physiologically siloed in four cone types is not well understood, and in larvae, cone physiological spectral peaks are unstudied. We use a spectral model to infer cone wavelength peaks, semisaturation irradiances, and saturation amplitudes from electroretinogram (ERG) datasets composed of multi-wavelength, multi-irradiance, aspartate-isolated, cone-PIII signals, as compiled from many 5- to 12-day larvae and 8- to 18-month-old adult eyes isolated from wild-type (WT) or roy orbison (roy) strains. Analysis suggests (in nm) a seven-cone, U-360/B1-427/B2-440/G1-460/G3-476/R1-575/R2-556, spectral physiology in WT larvae but a six-cone, U-349/B1-414/G3-483/G4-495/R1-572/R2-556, structure in WT adults. In roy larvae, there is a five-cone structure: U-373/B2-440/G1-460/R1-575/R2-556; in roy adults, there is a four-cone structure, B1-410/G3-482/R1-571/R2-556. Existence of multiple B, G, and R types is inferred from shifts in peaks with red or blue backgrounds. Cones were either high or low semisaturation types. The more sensitive, low semisaturation types included U, B1, and G1 cones [3.0–3.6 log(quanta·μm−2·s−1)]. The less sensitive, high semisaturation types were B2, G3, G4, R1, and R2 types [4.3-4.7 log(quanta·μm−2·s−1)]. In both WT and roy, U- and B- cone saturation amplitudes were greater in larvae than in adults, while G-cone saturation levels were greater in adults. R-cone saturation amplitudes were the largest (50–60% of maximal dataset amplitudes) and constant throughout development. WT and roy larvae differed in cone signal levels, with lesser UV- and greater G-cone amplitudes occurring in roy, indicating strain variation in physiological development of cone signals. These physiological measures of cone types suggest chromatic processing in zebrafish involves at least four to seven spectral signal processing pools.

The spectral tuning properties of the whale shark (Rhincodon typus) rod (rhodopsin or Rh1) and long-wavelength-sensitive (LWS) cone visual pigments were examined to determine whether these retinal pigments have adapted to the broadband light spectrum available for surface foraging or to the narrowband blue-shifted light spectrum available at depth. Recently published whale shark genomes have identified orthologous genes for both the whale shark Rh1 and LWS cone opsins suggesting a duplex retina. Here, the whale shark Rh1 and LWS cone opsin sequences were examined to identify amino acid residues critical for spectral tuning. Surprisingly, the predicted absorbance maximum (λmax) for both the whale shark Rh1 and LWS visual pigments is near 500 nm. Although Rh1 λmax values near 500 nm are typical of terrestrial vertebrates, as well as surface foraging fish, it is uncommon for a vertebrate LWS cone pigment to be so greatly blue-shifted. We propose that the spectral tuning properties of both the whale shark Rh1 and LWS cone pigments are most likely adaptations to the broadband light spectrum available at the surface. Whale shark melanopsin (Opn4) deactivation kinetics was examined to better understand the underlying molecular mechanisms of the pupillary light reflex. Results show that the deactivation rate of whale shark Opn4 is similar to the Opn4 deactivation rate from vertebrates possessing duplex retinae and is significantly faster than the Opn4 deactivation rate from an aquatic rod monochromat lacking functional cone photoreceptors. The rapid deactivation rate of whale shark Opn4 is consistent with a functional cone class and would provide the animal with an exponential increase in the number of photons required for photoreceptor signaling when transitioning from photopic to scotopic light conditions, as is the case when diving.

In primates and carnivores, the main laminae of the dorsal lateral geniculate nucleus (LGN) receive monocular excitatory input in an eye-alternating fashion. There is also evidence that nondominant eye stimulation can reduce responses to dominant eye stimulation and that a subset of LGN cells in the koniocellular (K) layers receives convergent binocular excitatory input from both eyes. What is not known is how the two eye inputs summate in the K layers of LGN. Here, we aimed to answer this question by making extracellular array electrode recordings targeted to K layers in the marmoset (Callithrix jacchus) LGN, as visual stimuli (flashed 200 ms temporal square-wave pulses or drifting gratings) were presented to each eye independently or to both eyes simultaneously. We found that when the flashed stimulus was presented to both eyes, compared to the dominant eye, the peak firing rate of most cells (61%, 14/23) was reduced. The remainder showed response facilitation (17%) or partial summation (22%). A greater degree of facilitation was seen when the total number of spikes across the stimulus time window (200 ms) rather than peak firing rates was measured. A similar pattern of results was seen for contrast-varying gratings and for small numbers of parvocellular (n = 12) and magnocellular (n = 3) cells recorded. Our findings show that binocular summation in the marmoset LGN is weak and predominantly sublinear in nature.

The trial-to-trial response variability in sensory cortices and the extent to which this variability can be coordinated among cortical units have strong implications for cortical signal processing. Yet, little is known about the relative contributions and dynamics of defined sources to the cortical response variability and their correlations across cortical units. To fill this knowledge gap, here we obtained and analyzed multisite local field potential (LFP) recordings from visual cortex of turtles in response to repeated naturalistic movie clips and decomposed cortical across-trial LFP response variability into three defined sources, namely, input, network, and local fluctuations. We found that input fluctuations dominate cortical response variability immediately following stimulus onset, whereas network fluctuations dominate the response variability in the steady state during continued visual stimulation. Concurrently, we found that the network fluctuations dominate the correlations of the variability during the ongoing and steady-state epochs, but not immediately following stimulus onset. Furthermore, simulations of various model networks indicated that (i) synaptic time constants, leading to oscillatory activity, and (ii) synaptic clustering and synaptic depression, leading to spatially constrained pockets of coherent activity, are both essential features of cortical circuits to mediate the observed relative contributions and dynamics of input, network, and local fluctuations to the cortical LFP response variability and their correlations across recording sites. In conclusion, these results show how a mélange of multiscale thalamocortical circuit features mediate a complex stimulus-modulated cortical activity that, when naively related to the visual stimulus alone, appears disguised as high and coordinated across-trial response variability.