Cone Signals Research Articles

Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses

Rod photoreceptors contribute to vision over an ∼ 6-log-unit range of light intensities. The wide dynamic range of rod vision is thought to depend upon light intensity-dependent switching between two parallel pathways linking rods to ganglion cells: a rod → rod bipolar (RB) cell pathway that operates at dim backgrounds and a rod → cone → cone bipolar cell pathway that operates at brighter backgrounds. We evaluated this conventional model of rod vision by recording rod-mediated light responses from ganglion and AII amacrine cells and by recording RB-mediated synaptic currents from AII amacrine cells in mouse retina. Contrary to the conventional model, we found that the RB pathway functioned at backgrounds sufficient to activate the rod → cone pathway. As background light intensity increased, the RB's role changed from encoding the absorption of single photons to encoding contrast modulations around mean luminance. This transition is explained by the intrinsic dynamics of transmission from RB synapses.

Saliency interactions between the ‘L-M’ and ‘S’ cardinal colour directions

Two sub-systems characterize the early stages of human colour vision, the 'L-M' system that differences L and M cone signals and the 'S' system that differences S cone signals from the sum of L and M cone signals. How do they interact at suprathreshold contrast levels? To address this question we employed the method used by Kingdom et al. (2010) to study suprathreshold interactions between luminance and colour contrast. The stimulus employed in one condition was similar to that used by Regan and Mollon (1997) for studying the relative 'organizing power' of the two sub-systems, and consisted of obliquely-oriented red-cyan (to isolate the L-M sub-system) and violet-chartreuse (to isolate the S sub-system) stripes within a lattice of circles. In our experiment there were two conditions, (1) the Separated condition, in which the L-M and S modulations were of opposite orientation and presented separately as a forced-choice pair, and (2) the Combined condition, in which the L-M and S modulations were added. In the Separated condition the task was to indicate the stimulus with the more salient orientation structure, whereas in the Combined condition the task was to indicate the orientation that was more salient. Psychometric functions were used to estimate the ratio of L-M to S contrast at the 'balance-point' i.e. point-of-subjective-equality (PSE) in both conditions. We found that across 20 subjects an average of 8% more S than L-M contrast was needed to achieve a PSE in the Combined compared to Separated condition. We consider possible reasons for this PSE difference and conclude that it is either due to an early-stage interaction between the S and L-M sub-systems, or to a later stage in which new colours that arise from their combination are selectively grouped.

Multispectral analysis and cone signal modelling of pseudoisochromatic test plates

The aim of the study is to determine the consistency of the desired colour reproduction of the stimuli using calibrated printing technology available to anyone (EpsonStylus Pro 7800 printer was). 24 colour vision assessment plates created in the University of Latvia were analysed right after their fabrication on august 2012 and after intense use for 7 months (colour vision screening on 700 people). Multispectral imagery results indicate that the alignment of the samples after seven months of use has maintained on the CIExy confusion lines of deutan deficiency type, but the shift towards achromatic area in the diagram indicate decrease in the total colour difference (ΔE*ab) of test background (achromatic) areas and stimuli (chromatic) areas, thus affecting the testing outcome and deficiency severity level classification ability of the plates.

Switching Responses: Spatial and Temporal Regulators of Axon Guidance

The ability of the axonal growth cone to switch between attraction and repulsion in response to guidance cues in the extracellular environment during nervous system development is fundamental to the precise wiring of complex neural circuits. Regulation of cell-surface receptors by means of transcriptional control, local translation, trafficking and proteolytic processing are powerful mechanisms to regulate the response of the growth cone. Important work has also revealed how intracellular signalling pathways, including calcium and cyclic nucleotide signalling, can alter the directional response elicited by a particular cue. Here, we describe how these multiple regulatory mechanisms influence growth cone turning behaviour. We focus on recent evidence that suggests a significant role for 14-3-3 adaptor proteins in modifying growth cone turning behaviour and mediating directional polarity switches during development. Characterizing how 14-3-3 s regulate growth cone signalling will provide invaluable insight into nervous system development and may facilitate the identification of novel targets for promoting nerve regeneration following injury.

Sign‐preserving and sign‐inverting synaptic interactions between rod and cone photoreceptors in the dark‐adapted retina

We show that various types of rods and cones in the dark-adapted salamander retina are electrically coupled with linear and symmetrical junctional conductances G(j) (40-223 pS) and a rank order: Rod(C)-large single cone, rod-large single cone, rod-small single cone, rod-accessory double cone and rod-principal double cone. By systematically comparing the transjunctional current-voltage (I(j)-V(j)) relations and average G(j) values of the five types of rod-cone pairs recorded at day and night times, our results suggest that the differences in G(j) values among various types of rod-cone pairs are not caused by circadian differences, and the circadian-dependent changes in rod-cone coupling observed in the fish and rodent retinas are not present in the tiger salamander. In addition to rod-cone coupling, there is a sign-inverting, unidirectional rod→cone current I(RC), and the I(RC)-V(Cone) relations are linear, with a reversal potential near the chloride reversal potential E(Cl). I(RC) can be observed in rods and cones separated by at least 260 μm, and its waveform resembles that of the rod-elicited horizontal cell (HC) response I(HC). A glutamate transporter-associated chloride channel blocker TBOA suppresses I(RC) but not I(HC). These results suggest that I(RC) is largely mediated by HCs via a sign-inverting feedback chemical synapse associated with a chloride channel. I(RC) significantly reduced rod→cone coupling in the frequency range below 15 Hz, allowing better separation of rod and cone signals in the dark-adapted retina.

Processing of the S-cone signals in the early visual cortex of primates

The short-wavelength-sensitive (S) cones play an important role in color vision of primates, and may also contribute to the coding of other visual features, such as luminance and motion. The color signals carried by the S cones and other cone types are largely separated in the subcortical visual pathway. Studies on nonhuman primates or humans have suggested that these signals are combined in the striate cortex (V1) following a substantial amplification of the S-cone signals in the same area. In addition to reviewing these studies, this review describes the circuitry in V1 that may underlie the processing of the S-cone signals and the dynamics of this processing. It also relates the interaction between various cone signals in V1 to the results of some psychophysical and physiological studies on color perception, which leads to a discussion of a previous model, in which color perception is produced by a multistage processing of the cone signals. Finally, I discuss the processing of the S-cone signals in the extrastriate area V2.

Distinct synaptic mechanisms create parallel S-ON and S-OFF color opponent pathways in the primate retina

Anatomical and physiological approaches are beginning to reveal the synaptic origins of parallel ON- and OFF-pathway retinal circuits for the transmission of short (S-) wavelength sensitive cone signals in the primate retina. Anatomical data suggest that synaptic output from S-cones is largely segregated; central elements of synaptic triads arise almost exclusively from the "blue-cone" bipolar cell, a presumed ON bipolar, whereas triad-associated contacts derive primarily from the "flat" midget bipolar cell, a hyperpolarizing, OFF bipolar. Similarly, horizontal cell connectivity is also segregated, with only the H2 cell-type receiving numerous contacts from S-cones. Negative feedback from long (L-) and middle (M-) wavelength sensitive cones via the H2 horizontal cells elicits an antagonistic surround in S-cones demonstrating that S versus L + M or "blue-yellow" opponency is first established in the S-cone. However, the S-cone output utilizes distinct synaptic mechanisms to create color opponency at the ganglion cell level. The blue-cone bipolar cell is presynaptic to the small bistratified, "blue-ON" ganglion cell. S versus L + M cone opponency arises postsynaptically by converging S-ON and LM-OFF excitatory bipolar inputs to the ganglion cell's bistratified dendritic tree. The common L + M cone surrounds of the parallel S-ON and LM-OFF cone bipolar inputs appear to cancel resulting in "blue-yellow" antagonism without center-surround spatial opponency. By contrast, in midget ganglion cells, opponency arises by the differential weighting of cone inputs to the receptive field center versus surround. In the macula, the "private-line" connection from a midget ganglion cell to a single cone predicts that S versus L + M opponency is transmitted from the S-cone to the S-OFF midget bipolar and ganglion cell. Beyond the macula, OFF-midget ganglion cell dendritic trees enlarge and collect additional input from multiple L and M cones. Thus S-OFF opponency via the midget pathway would be expected to become more complex in the near retinal periphery as L and/or M and S cone inputs sum to the receptive field center. An important goal for further investigation will be to explore the hypothesis that distinct bistratified S-ON versus midget S-OFF retinal circuits are the substrates for human psychophysical detection mechanisms attributed to S-ON versus S-OFF perceptual channels.

Inhibition to retinal rod bipolar cells is regulated by light levels

The retina responds to a wide range of light stimuli by adaptation of retinal signaling to background light intensity and the use of two different photoreceptors: rods that sense dim light and cones that sense bright light. Rods signal to rod bipolar cells that receive significant inhibition from amacrine cells in the dark, especially from a rod bipolar cell-activated GABAergic amacrine cell. This inhibition modulates the output of rod bipolar cells onto downstream neurons. However, it was not clear how the inhibition of rod bipolar cells changes when rod signaling is limited by an adapting background light and cone signaling becomes dominant. We found that both light-evoked and spontaneous rod bipolar cell inhibition significantly decrease with light adaptation. This suggests a global decrease in the activity of amacrine cells that provide input to rod bipolar cells with light adaptation. However, inhibition to rod bipolar cells is also limited by GABAergic connections between amacrine cells, which decrease GABAergic input to rod bipolar cells. When we removed this serial inhibition, the light-evoked inhibition to rod bipolar cells remained after light adaptation. These results suggest that decreased inhibition to rod bipolar cells after light adaptation is due to decreased rod pathway activity as well as an active increase in inhibition between amacrine cells. Together these serve to limit rod bipolar cell inhibition after light adaptation, when the rod pathway is inactive and modulation of the signal is not required. This suggests an efficiency mechanism in the retina to limit unnecessary signaling.

A distributed code for color in natural scenes derived from center-surround filtered cone signals

In the retina of trichromatic primates, chromatic information is encoded in an opponent fashion and transmitted to the lateral geniculate nucleus (LGN) and visual cortex via parallel pathways. Chromatic selectivities of neurons in the LGN form two separate clusters, corresponding to two classes of cone opponency. In the visual cortex, however, the chromatic selectivities are more distributed, which is in accordance with a population code for color. Previous studies of cone signals in natural scenes typically found opponent codes with chromatic selectivities corresponding to two directions in color space. Here we investigated how the non-linear spatio-chromatic filtering in the retina influences the encoding of color signals. Cone signals were derived from hyper-spectral images of natural scenes and preprocessed by center-surround filtering and rectification, resulting in parallel ON and OFF channels. Independent Component Analysis (ICA) on these signals yielded a highly sparse code with basis functions that showed spatio-chromatic selectivities. In contrast to previous analyses of linear transformations of cone signals, chromatic selectivities were not restricted to two main chromatic axes, but were more continuously distributed in color space, similar to the population code of color in the early visual cortex. Our results indicate that spatio-chromatic processing in the retina leads to a more distributed and more efficient code for natural scenes.

Neurophysiological correlates of color vision: A model.

tree-receptor theory of human color vision accounts for color matching. A bottom-up, non-linear model combining cone signals in six types of cone-opponent cells in the lateral geniculate nucleus (LGN) of primates describes the phenomenological dimensions hue, color strength, and lightness/brightness. Hue shifts with light intensity (the Bezold-Brucke phenomenon), and saturation (the Abney effect) are also accounted for by the opponent model. At the threshold level, sensitivities of the more sensitive primate cells correspond well with human psychophysical thresholds. Conventional Fourier analysis serves well in dealing with the discrimination data, but here we want to take a look at non-linearity, i.e., the neural correlates to perception of color phenomena for small and large fields that span several decades of relative light intensity. We are particularly interested in the mathematical description of spectral opponency, receptive fields, the balance of excitation and inhibition when stimulus size changes, and retina-to-LGN thresholds. Keywords: human color vision, opponent theory, three-color theory, three-receptor theory, perception, neuroscience.

Endocannabinoids via CB1receptors act as neurogenic niche cues during cortical development

During brain development, neurogenesis is precisely regulated by the concerted action of intrinsic factors and extracellular signalling systems that provide the necessary niche information to proliferating and differentiating cells. A number of recent studies have revealed a previously unknown role for the endocannabinoid (ECB) system in the control of embryonic neuronal development and maturation. Thus, the CB(1) cannabinoid receptor in concert with locally produced ECBs regulates neural progenitor (NP) proliferation, pyramidal specification and axonal navigation. In addition, subcellularly restricted ECB production acts as an axonal growth cone signal to regulate interneuron morphogenesis. These findings provide the rationale for understanding better the consequences of prenatal cannabinoid exposure, and emphasize a novel role of ECBs as neurogenic instructive cues involved in cortical development. In this review the implications of altered CB(1)-receptor-mediated signalling in developmental disorders and particularly in epileptogenesis are briefly discussed.

The contribution of the rod/melanopsin driven ganglion cells to the dynamic pupil light reflex response

AbstractPurpose Intrinsically photosensitive retinal ganglion cells have been shown to contribute to the control of the steady‐state pupil response. The extent to which melanopsin contributes to rapid pupil responses elicited with brief stimuli remains less clear. The principal objective of this study was to examine how the dynamic pupil light reflex response changes with the level of light adaptation for stimuli that isolate luminance, colour or combined rod and melanopsin. The range of light levels that yield useful rod signals was also investigated.Methods The study involved ten normal subjects, one patient with rod deficiency, one patient with retinitis pigmentosa (RP) and one rod monochromat. The pupil responses were measured to stimuli that isolate photopic luminance, colour or combined rod and melanopsin at three light levels (456, 74.4 and 4.8cd/m2). Visual acuity, contrast sensitivity and chromatic sensitivity were also measured in all subjects.Results The patients with rod deficiency and RP exhibit pupil responses to luminance and colour modulation, but much reduced or absent response to rod/melanopsin modulation. Conversely, the rod monochromat shows complete absence of pupil colour and luminance responses, but exhibits large pupil rod/melanopsin responses at all light levels.Conclusion The findings from this study suggest that pupil responses to briefly presented stimuli are mediated largely by rod and cone signals with no contribution from melanopsin. The results also suggest that rod signals remain unsaturated and can contribute to dynamic pupil responses at much higher light levels.

Colour and pattern selectivity of receptive fields in superior colliculus of marmoset monkeys

The main subcortical visual targets of retinal output neurones (ganglion cells) are the parvocellular and magnocellular layers of the dorsal lateral geniculate nucleus (LGN) in the thalamus. In addition, a small and heterogeneous collection of ganglion cell axons projects to the koniocellular layers of the LGN, to the superior colliculus (SC), and to other subcortical targets. The functional (receptive field) properties and target specificity of these non-parvocellular, non-magnocellular populations remain poorly understood. It is known that one population of koniocellular layer cells in the LGN (blue-On cells) receives dominant functional input from short-wavelength sensitive (S or ‘blue') cones. Here we asked whether SC neurones also receive S cone inputs. We made extracellular recordings from single neurones (n = 38) in the SC of anaesthetised marmoset monkeys. Responses to drifting and flashed gratings providing defined levels of cone contrast were measured. The SC receptive fields we recorded were often binocular, showed ‘complex cell' like responses (On–Off responses), strong bandpass spatial frequency tuning, direction selectivity, and many showed strong and rapid habituation to repeatedly presented stimuli. We found no evidence for dominant S cone input to any SC neurone recorded. These data suggest that S cone signals may reach cortical pathways for colour vision exclusively through the koniocellular division of the lateral geniculate nucleus.

Organizational motifs for ground squirrel cone bipolar cells

In daylight vision, parallel processing starts at the cone synapse. Cone signals flow to On and Off bipolar cells, which are further divided into types according to morphology, immunocytochemistry, and function. The axons of the bipolar cell types stratify at different levels in the inner plexiform layer (IPL) and can interact with costratifying amacrine and ganglion cells. These interactions endow the ganglion cell types with unique functional properties. The wiring that underlies the interactions among bipolar, amacrine, and ganglion cells is poorly understood. It may be easier to elucidate this wiring if organizational rules can be established. We identify 13 types of cone bipolar cells in the ground squirrel, 11 of which contact contiguous cones, with the possible exception of short-wavelength-sensitive cones. Cells were identified by antibody labeling, tracer filling, and Golgi-like filling following transduction with an adeno-associated virus encoding for green fluorescent protein. The 11 bipolar cell types displayed two organizational patterns. In the first pattern, eight to 10 of the 11 types came in pairs with partially overlapping axonal stratification. Pairs shared morphological, immunocytochemical, and functional properties. The existence of similar pairs is a new motif that might have implications for how signals first diverge from a cone to bipolar cells and then reconverge onto a costratifying ganglion cell. The second pattern is a mirror symmetric organization about the middle of the IPL involving at least seven bipolar cell types. This anatomical symmetry may be associated with a functional symmetry in On and Off ganglion cell responses.

Light-Driven Calcium Signals in Mouse Cone Photoreceptors

Calcium mediates various neuronal functions. The complexity of neuronal Ca²⁺ signaling is well exemplified by retinal cone photoreceptors, which, with their distinct compartmentalization, offer unique possibilities for studying the diversity of Ca²⁺ functions in a single cell. Measuring subcellular Ca²⁺ signals in cones under physiological conditions is not only fundamental for understanding cone function, it also bears important insights into pathophysiological processes governing retinal neurodegeneration. However, due to the proximity of light-sensitive outer segments to other cellular compartments, optical measurements of light-evoked Ca²⁺ responses in cones are challenging. We addressed this problem by generating a transgenic mouse (HR2.1:TN-XL) in which both short- and middle-wavelength-sensitive cones selectively express the genetically encoded ratiometric Ca²⁺ biosensor TN-XL. We show that HR2.1:TN-XL allows recording of light-evoked Ca²⁺ responses using two-photon imaging in individual cone photoreceptor terminals and to probe phototransduction and its diverse regulatory mechanisms with pharmacology at subcellular resolution. To further test this system, we asked whether the classical, nitric oxide (NO)-soluble guanylyl-cyclase (sGC)-cGMP pathway could modulate Ca²⁺ in cone terminals. Surprisingly, NO reduced Ca²⁺ resting levels in mouse cones, without evidence for direct sGC involvement. In conclusion, HR2.1:TN-XL mice offer unprecedented opportunities to elucidate light-driven Ca²⁺ dynamics and their (dys)regulation in cone photoreceptors.

Nonlinear analysis of macaque V1 color tuning reveals cardinal directions for cortical color processing.

Understanding color vision requires knowing how signals from the three classes of cone photoreceptor are combined in the cortex. We recorded from single V1 neurons in awake monkeys while an automated, closed-loop system identified stimuli that differed in cone contrast but evoked the same response. We found that isoresponse surfaces for about half the neurons were planar, consistent with linear processing. The remaining isoresponse surfaces were nonplanar. Some were cup-shaped, indicating sensitivity to a narrow region of color space. Others were ellipsoidal, indicating sensitivity to all color directions. The major and minor axes of these nonlinear surfaces were often aligned to a set of three color directions that were previously identified in perceptual experiments. These results demonstrate that many V1 neurons combine cone signals nonlinearly and provide a new framework within which to decipher color processing in V1.

The Mode of Retinal Presynaptic Inhibition Switches with Light Intensity

Excitatory amino acid transporters (EAATs) terminate signaling in the CNS by clearing released glutamate. Glutamate also evokes an EAAT-mediated Cl(-) current, but its role in CNS signaling is poorly understood. We show in mouse retina that EAAT-mediated Cl(-) currents that were evoked by light inhibit rod pathway signaling. EAATs reside on rod bipolar cell axon terminals where GABA and glycine receptors also mediate light-evoked inhibition. We found that the mode of inhibition depended on light intensity. Dim light evoked GABAergic and glycinergic inhibition with rapid kinetics and a large spatial extent. Bright light evoked predominantly EAAT-mediated inhibition with slow kinetics and a small spatial extent. The switch to EAAT-mediated signaling in bright light supplements receptor-mediated signaling to expand the dynamic range of inhibition and contributes to the transition from rod to cone signaling by suppressing rod pathway signaling in bright light conditions.

Proton feedback mediates the cascade of color-opponent signals onto H3 horizontal cells in goldfish retina

It has been postulated that horizontal cells (HCs) send feedback signals onto cones via a proton feedback mechanism, which generates the center-surround receptive field of bipolar cells, and color-opponent signals in many non-mammalian vertebrates. Here we used a strong pH buffer, HEPES, to reduce extracellular proton concentration changes and so determine whether protons mediate color-opponent signals in goldfish H3 (triphasic) HCs. Superfusion with 10mM HEPES-fortified saline elicited depolarization of H3 HCs’ dark membrane potential and enhanced hyperpolarizing responses to blue stimuli, but suppressed both depolarization by yellow and orange and hyperpolarization by red stimuli. The response components suppressed by HEPES resembled the inverse of spectral responses of H2 (biphasic) HCs. These results are consistent with the Stell–Lightfoot cascade model, in which the HEPES-suppressed component of H3 HCs was calculated using light responses recorded experimentally in H1 (monophasic) and H2 HCs. Selective suppression of long- or long-+middle-wavelength cone signals by long-wavelength background enhanced the responses to short-wavelength stimuli. These results suggest that HEPES inhibited color opponent signals in H3 HCs, in which the source of opponent-color signals is primarily a feedback from H2 HCs and partly from H1 HCs onto short-wavelength cones, probably mediated by protons.

Contrast adaptation reveals increased organizational complexity of chromatic processing in the visual evoked potential

Results from psychophysics and single-unit recordings suggest that color vision comprises multiple stages of processing. Postreceptoral channels appear to consist of both a stage of broadly tuned opponent channels that compare cone signals and a subsequent stage, which includes cells tuned to many different directions in color space. The chromatic visual evoked potential (crVEP) has demonstrated chromatic processing selective for cardinal axes of color space. However, crVEP evidence for higher-order color mechanisms is lacking. The present study aimed to assess the contribution of lower- and higher-order color mechanisms to the crVEP by using chromatic contrast adaptation. The results reveal the presence of mechanisms tuned to intermediate directions in color space in addition to those tuned to the fundamental cardinal axes.

Color appearance at ±10° along the vertical and horizontal meridians

Hue-scaling data were collected from three observers using the "4+1" color-naming procedure for circular (0.25°-5°), monochromatic (440-660 nm) stimuli. Stimuli were presented at ±10° along the vertical and horizontal meridians under conditions chosen to include both rod and cone signals (no bleach) and to minimize rod contribution (bleach). All color-naming data were analyzed and compared using uniform appearance diagrams. Smaller stimuli appear more desaturated under both bleach conditions. This effect is particularly detrimental for the perception of green and is influenced by retinal location and exacerbated with rod input. As stimulus size increases and perceptive field sizes are filled for all four elemental hues, the differences in hue perception among the four peripheral locations and the two bleach conditions are attenuated. Results are consistent with predictions based on known differences in the underlying retinal mosaic among the four locations.