Visual evoked responses to dichoptically presented multifocal stimuli were recorded for 92 eyes. Two stimulus variants were explored: temporally sparse and rapidly contrast reversing. We used hierarchal decomposition (HD) to represent the multifocal responses in terms of a small number of potentially unique component waveforms that are interrelated in a multivariate linear autoregressive (MLAR) relationship. The HD method exploits temporal correlations over a range of delays in the responses to estimate parallel, feedforward and feedback relationships between the HD components. Three HD components having temporal interrelationships constrained (at P < 0.05) to a moving ∼20 ms window could describe the multifocal responses well (median r2-values up to 90%). HD components were similar for both stimulus types and the component waveforms were temporally correlated, especially the first and third components. The data set was large enough to estimate separate HD components for each multifocal stimulus region. The component waveforms differed somewhat by region but the MLAR relationships were similar. At short delays parallel processing dominated. At longer delays the proportion of response drives that were attributed to feedback and feedforward relationships grew. Overall HD analysis seems to provide an informed summary of multifocal responses and insights into their sources.

Gap junctions provide a pathway for the direct intercellular exchange of ions and small signaling molecules. Gap junctional coupling between retinal astrocytes and between astrocytes and Müller cells, the principal glia of vertebrate retinas, has been previously demonstrated by the intercellular transfer of gap-junction permeant tracers. However, functional gap junctions have yet to be demonstrated between mammalian Müller cells. In the present study, when the gap-junction permeant tracers Neurobiotin and Lucifer yellow were injected into a Müller cell via a patch pipette, the tracers transferred to at least one additional cell in more than half of the cases examined. Simultaneous whole-cell recordings from pairs of Müller cells in the isolated rabbit retina revealed electrical coupling between closely neighboring cells, confirming the presence of functional gap junctions between rabbit Müller cells. The limited degree of this coupling suggests that Müller cell–Müller cell gap junctions may coordinate the functions of small ensembles of these glial cells. Immunohistochemistry and immunoblotting were used to identify the connexins in rabbit retinal glia. Connexin30 (Cx30) and connexin43 (Cx43) immunoreactivities were associated with astrocytes in the medullary ray region of the retinas of both pigmented and albino rabbits. Connexin43 was also found in Müller cells, but antibody recognition differed between astrocytic and Müller cell connexin43.

The role of sensory experience in the development and plasticity of the visual system has been widely studied. It has generally been reported that once animals reach adulthood, experience-dependent visual plasticity is reduced. We have found that visual experience is not needed for the refinement of receptive fields (RFs) in the superior colliculus (SC) but instead is necessary to maintain them in adulthood (Carrasco et al., 2005). Without light exposure, RFs in SC of hamsters refine by postnatal day 60 as usual but then enlarge, presumably reducing visual acuity. In this study we examine whether a brief period of light exposure during early postnatal development would be sufficient to prevent RF enlargement in adulthood, and whether prolonged light exposure in adulthood could reverse the deprivation-induced increase in RF size. We found that an early postnatal period of at least 30 days of visual experience was sufficient to maintain refined RFs in the adult SC. Prolonged visual experience in adulthood could not reverse the RF enlargement resulting from long-term dark rearing, reflecting a loss of plasticity at this age. Our results suggest that, unlike in visual cortex, dark rearing does not indefinitely extend the critical period of plasticity in SC. Rather, there is a limited time window when early experience can protect RFs from the detrimental effects of visual deprivation in adulthood. These results contribute to understanding adult brain plasticity and argue for the importance of early visual experience in protecting the adult visual system.

The International Colour Vision Society awarded the 2005 Verriest Medal to John D. Mollon, Professor of Visual Neuroscience at the University of Cambridge, UK. This award is bestowed by the Society to honor long-term contributions to the field of color vision. If the field of color vision were itself a rainbow, then Professor Mollon's contributions cover nearly its full spectrum, including the isolation and elucidation of basic chromatic coding mechanisms and the constraints that they impose on human (and more generally primate) visual performance, the genetic basis of spectral coding mechanisms, the ecological influences on and evolutionary origins of chromatic discrimination. He has been instrumental in the design of several new color vision tests and has extensively exploited abnormal models, both congenital and acquired, to further our understanding of normal mechanisms. He is especially appreciated for his keen and profound sense of the history of science, in particular with respect to the field of color vision. He has been a member of the society for over 25 years and is currently serving on its board of directors. He organized the 2001 ICVS meeting in Cambridge, celebrating the bicentennial of Thomas Young's lecture on color vision.

Bipolar cells were recorded in rat retinal slices to study the distribution of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels. Patch-clamp whole cell measurements were combined with intracellular filling and recorded cells were morphologically identified. HCN channel isoforms HCN1-4 are differentially expressed in bipolar cells. Each bipolar cell type has a characteristic inventory of HCN channels. The combination of HCN channel currents and other voltage-gated currents can be used as a kind of “finger print” to electrophysiologically identify and classify bipolar cell types. Using this approach of combined electrophysiological and morphological classification we could identify a new ON-cone bipolar cell type.

Melatonin is a ubiquitous molecule and widely distributed in nature, with functional activity occurring in unicellular organisms, plants, fungi, and animals. Several studies have indicated that melatonin synthesis occurs in the retina of most vertebrates, including mammals. The retinal biosynthesis of melatonin and the mechanisms involved in the regulation of this process have been extensively studied. Circadian clocks located in the photoreceptors and retinal neurons regulate melatonin synthesis in the eye. Photoreceptors, dopaminergic amacrine neurons, and horizontal cells of the retina, corneal epithelium, stroma endothelium, and the sclera all have melatonin receptors, indicating a widespread ocular function for melatonin. In addition, melatonin is an effective antioxidant which scavenges free radicals and up-regulates several antioxidant enzymes. It also has a strong antiapoptotic signaling function, an effect that it exerts even during ischemia. Melatonin cytoprotective properties may have practical implications in the treatment of ocular diseases, like glaucoma and age-related macular degeneration.

Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in the Cacna1f gene, encoding the α1F subunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in the nob2 (no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation in Cacna1f. Not surprisingly, the b-waves of both the light- and dark-adapted electroretinogram are abnormal in nob2 mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cells in vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate that nob2 mice are a valuable model in which to explore the pathophysiological mechanisms associated with Cacna1f mutations causing CSNB2, and the subsequent effects on visual information processing. Further, the nob2 mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.

We assessed the growth of the rat photopic electroretinogram (ERG) during light adaptation and the mechanisms underlying this process. Full field ERG responses were recorded from anesthetized adult Brown–Norway rats at each minute for 20 min of light adaptation (backgrounds: 1.8, 2.1, 2.4 log scotopic cd m−2). The rat photopic b-wave amplitude increased with duration of light adaptation and its width at 33% maximal amplitude narrowed (by ∼ 40 ms). These effects peaked 12–15 min after background onset. The narrowing of the b-wave reflected steepening of the b-wave recovery phase, with little change in the rising phase. OP amplitudes grew in proportion to the b-wave. Inhibition of inner retinal responses using TTX resulted in a greater relative growth of b-wave and OP amplitude compared with fellow control eyes, and delayed the change in recovery phase by ∼ 5 min. Inhibition of all ionotropic glutamate receptors with CNQX/D-AP7 delayed both rising and recovery phases equally (∼ 12 ms) without altering b-wave width or the time course of adaptation changes. These outcomes suggest that inner retinal light responses are not directly responsible for b-wave amplitude growth, but may contribute to the change in its recovery phase during adaptation. A TTX-sensitive mechanism may help to hasten this process. The cone a-wave was isolated using PDA/L-AP4 or CNQX/L-AP4. A-wave amplitude (35 ms after stimulus onset) also increased with time during light adaptation and reached a maximum (130 ± 29% above baseline) 12–15 min after background onset. B-wave amplitude growth in fellow control eyes closely followed the course and relative magnitude of cone a-wave amplitude growth. Hence, the increase of the cone response during light adaptation is sufficient to explain b-wave amplitude growth.

The International Colour Vision Society (ICVS) held its 18th biennial meeting in Lyon, France in July 2005. The ICVS, originally founded in 1967 as the International Research Group in Colour Vision Deficiencies and renamed in 1997, brings together vision scientists and clinicians with a common interest in color vision and color vision deficiencies. With significant technological advances that have permitted new and deeper questions about color vision to be addressed, the subject matter of recent meetings has expanded to include greater contributions from such areas as molecular genetics and evolution, retinal and cerebral imaging studies and computational modeling. The peer-reviewed papers in this volume span these newer and the more traditional topics of interest to the society, covering both applied and fundamental topics.

The nucleus isthmi (NI) of the frog receives input from the ipsilateral optic tectum and projects back to both optic tecta. After ablation of NI, frogs display no visually elicited prey-catching or threat avoidance behavior. Neural mechanisms that underlie the loss of such important behavior have not been solved. Electrophysiological examination of the contralateral isthmotectal projection has proved that it contributes to binocular vision. On the other hand, there are very few physiological investigations of the ipsilateral isthmotectal projection. In this study, current source density (CSD) analysis was applied to contra- and ipsilateral isthmotectal projections. The contralateral projection produced monosynaptic sinks in superficial layers and in layer 8. The results confirmed former findings obtained by single unit recordings. The ipsilateral projection elicited a prominent monosynaptic sink in layer 8. Recipient neurons were located in layers 6–7. These results, combined with those from the former intracellular study, led to the following neuronal circuit. Afferents from the ipsilateral NI inhibit non-efferent pear shaped neurons in the superficial layers, and strongly excite large ganglionic neurons projecting to the descending motor regions. Thus feedback to the output neurons strengthens the visually elicited responses.

The abundance and spatial distribution of retinal cone photoreceptors change during thyroid hormone (TH)-induced and natural development of rainbow trout (Oncorhynchus mykiss). These changes are thought to allow the fish to adapt to different photic environments throughout its life history. To date, the ontogeny of rainbow trout cone photoreceptors has been examined using physiological and morphological approaches. In this study, we extended these observations by measuring opsin gene expression in retinal quadrants during natural and TH-induced development. Gene expression during natural development was investigated in retinae from fish at both parr and smolt stages. The role of TH in modulating opsin gene expression was determined in TH-treated parr and control fish sampled after two, nine, and 22 days of treatment. Total RNA was isolated from each retinal quadrant and steady-state opsin mRNA levels were measured using reverse transcriptase real-time quantitative polymerase chain reaction (QPCR) analysis. Expression of ultraviolet-sensitive opsin (SWS1), rod opsin (RH1), middle wavelength-sensitive opsin (RH2), and long wavelength-sensitive opsin (LWS) transcripts vary spatially in the parr retina. Smolts, compared to parr, had downregulated SWS1 expression in all quadrants, lower LWS expression dorsally, higher RH1 expression nasally, and higher RH2 expression dorsally. In TH-treated parr, SWS1 opsin expression was downregulated in the nasal quadrants by two days. SWS1 displayed the greatest degree of downregulation in all quadrants after nine days of treatment, with an increase in short wavelength-sensitive (SWS2) and RH2 opsin mRNA expression in the temporal quadrants. This study reveals that opsin genes display spatially significant differences within rainbow trout retina in their level of mRNA expression, and that regulation of opsin expression is a dynamic process that is influenced by TH. This is particularly evident for SWS1 gene expression in parr following TH-induced and natural development.

Age-related maculopathy (ARM) has become the major cause of blindness in the Western World. Currently its pathogenesis and primary site of functional damage is not fully understood but ischemia is believed to play a major role. Early detection and precise monitoring of progression of ARM are main goals of current research due to lack of sufficient treatment options, especially in the dry, atrophic form of this disease. We applied the multifocal electroretinogram (mfERG) that can detect any local functional deficit objectively in the central retina. We recorded two paradigms in early ARM patients, the fast flicker and the slow flash paradigm which both represent fast adaptation processes of the proximal retina but under differing photopic conditions and stimulation rates. By subtracting the waveform responses we extracted a late component in the difference waveform that was significantly reduced in the early ARM group compared to a healthy control group (p ≤ 0.05). We propose that this multifocal nonlinear analysis permits the detection of adaptative deficits and provides topographic mapping of retinal dysfunction in early ARM. The difference waveform component we extracted with this novel approach might indicate early functional loss in ARM caused by ischemia in postreceptoral layers such as bipolar cells and inner plexiform regions.

Albino vertebrates exposed to intense light typically lose photoreceptors via apoptosis, and thus serve as useful models of retinal degeneration. In contrast, albino rainbow trout exposed to intense light maintain populations of rod and cone nuclei despite substantial damage to rod outer segments (ROS). The aim of this study was to differentiate between two hypotheses that could account for this divergent result: (1) trout rod nuclei remain intact during light damage, or (2) rod nuclei die but are replaced by cell proliferation. A further aim was to examine whether photic history modulates retinal damage, as in rodents. Albino and normally pigmented trout were moved from defined photic regimes into full daylight, while some were not moved to serve as protected controls. ROS were always maintained in pigmented fish and in albinos protected from full daylight. In albinos exposed to full daylight, ROS were removed over most of the central retina, whereas rod nuclei were maintained in the outer nuclear layer over 10 days. Pyknotic and TUNEL-labeled rod nuclei were abundant in affected albinos at all time-points tested. Rod death occurred without a decrease in the number of rod nuclei, confirming that proliferation must be replacing cells. Indeed a transient increase in proliferation was observed in retinal progenitors of albinos receiving 5 days of damaging light. This proliferative response was decreased with further damage. Cones remained intact even in areas where rod nuclei had degenerated. Pretreatment with light of moderate versus low intensity light affected the cell death and proliferative responses, and the ectopic localization of rod opsin. We conclude that apoptotic demise of rods, but not cones, occurred during light damage in retinas of albino trout and proliferative responses have a limited a capacity to replace lost rods.

In 1789, when neither the physical basis of hue nor the retinal basis of color perception was established, the mathematician Gaspard Monte stated firmly that our color perceptions do not depend on the absolute value of the physical variable, but are influenced by the context and in particular by our estimate of the illuminant. He used this insight to explain color contrast effects and the Paradox of Monge (the desaturation of red objects seen through a red filter). He proposed that we can estimate the chromaticity of the illuminant in any scene because all surfaces reflect to us varying mixtures of (i) the body color and (ii) a specular component that represents the illuminant. He also realized that white objects have a special property: Provided that they are illuminated by a single illuminant, such objects exhibit no variation in chromaticity across their surface. Thus at least one of the unique hues exists as an external reference on which observers can agree. It is suggested that other unique hues may also have a basis in the external world.

Contextual modulations of receptive field properties by distal stimulus configurations have been shown for a variety of stimulus paradigms. A survey of excitatory contextual modulation data for V1 shows the maximum scale of interactions, measured in terms of distance in V1, to be between 10 mm and 30 mm. Different types of excitatory contextual modulation in V1 occur throughout the interval of 40–250 ms after stimulus delivery. This window provides opportunity for global propagation of visual contextual information to a subset of V1 neurons, via several routes within the visual system. We propose a number of experiments and analyses to confirm the results from this empirical survey.

Afterpotentials of A-type horizontal cells (HCs) are believed to be rod-induced. They are, however, complex potentials and evidently of multiple causation. That part of the HC potential immediately after light-off is not entirely rod-determined because it has the same spectral sensitivity as the response to light-on, which is cone-induced with only some rod influence. It persists during a strong blue adapting light, which suppresses rod activity. The afterpotential may also be influenced by feedback from HCs to photoreceptors. The later part of the afterpotentials of A-type HCs is, however, rod dominated, as are the afterpotentials of axon terminals of B-type HCs.

The discontinuities of phase-shifted abutting line gratings give rise to perception of an “illusory contour” (IC) along the line terminations. Neuronal responses to such ICs have been interpreted as evidence for a specialized visual mechanism, since such responses cannot be predicted from conventional linear receptive fields. However, when the spatial scale of the component gratings (carriers) is large compared to the neuron's luminance passband, these IC responses might be evoked simply by the luminance edges at the line terminations. Thus by presenting abutting gratings at a series of carrier spatial scales to cat A18 neurons, we were able to distinguish genuine nonlinear responses from those due to luminance edges. Around half of the neurons (both simple and complex types) showed a bimodal response pattern to abutting gratings: one peak at a low carrier spatial frequency range that overlapped with the luminance passband, and a second distinct peak at much higher frequencies beyond the neuron's grating resolution. For those bimodally responding neurons, the low-frequency responses were sensitive to carrier phase, but the high-frequency responses were phase-invariant. Thus the responses at low carrier spatial frequencies could be understood via a linear model, while the higher frequency responses represented genuine nonlinear IC processing. IC responsive neurons also demonstrated somewhat lower spatial preference to the periodic contours (envelopes) compared to gratings, but the optimal orientation and motion direction for both were quite similar. The nonlinear responses to ICs could be explained by the same energy mechanism underlying responses to second-order stimuli such as contrast-modulated gratings. Similar neuronal preferences for ICs and for gratings may contribute to the form-cue invariant perception of moving contours.

We report the results of psychophysical experiments with the so-called barber pole stimulus providing new insights on the neuronal processes underlying the analysis of moving features such as terminators or line-endings. In experiment 1, we show that the perceived direction of a barber pole stimulus, induced by line-ending motion, is highly dependent on the spatial frequency and contrast of the grating stimulus: perceived direction is shifted away from the barber pole illusion at high spatial frequency in a contrast dependent way, suggesting that line-ends are not processed at high spatial scales. In subsequent experiments, we use a contrast adaptation paradigm and a masking paradigm in an attempt to assess the spatial structure and location of the receptive fields that process line-endings. We show that the adapting stimulus that weakens most the barber pole illusion is localized within the barber pole stimulus and not at line-endings' locations. Current models of line-endings' motion processing are discussed in the light of these psychophysical results.

Intracellular recordings were obtained from 57 cone-driven bipolar cells in the light-adapted retina of the land-phase (adult) tiger salamander (Ambystoma tigrinum). Responses to flashes of negative and positive contrast for centered spots of optimum spatial dimensions were analyzed as a function of contrast magnitude. On average, the contrast/response curves of depolarizing and hyperpolarizing bipolar cells in the land-phase animals were remarkably similar to those of aquatic-phase animals. Thus, the primary retinal mechanisms mediating contrast coding in the outer retina are conserved as the salamander evolves from the aquatic to the land phase. To evaluate contrast encoding in the context of natural environments, the distribution of contrasts in natural images was measured for 65 scenes. The results, in general agreement with other reports, show that the vast majority of contrasts in nature are very small. The efficient coding hypothesis of Laughlin was examined by comparing the average contrast/response curves of bipolar cells with the cumulative probability distribution of contrasts in natural images. Efficient coding was found at 20 cd/m2 but at lower levels of light adaptation, the contrast/response curves were much too shallow. Further experiments show that two fundamental physiological factors—light adaptation and the nonlinear transfer across the cone-bipolar synapse are essential for the emergence of efficient contrast coding. For both land- and aquatic-based animals, the extent and symmetry of the dynamic range of the contrast/response curves of both classes of bipolar cells varied greatly from cell to cell. This apparent substrate for distributed encoding is established at the bipolar cell level, since it is not found in cones. As a result, the dynamic range of the bipolar cell population brackets the distribution of contrasts found in natural images.

Researchers studying surface color perception have typically used stimuli that consist of a small number of matte patches (real or simulated) embedded in a plane perpendicular to the line of sight (a “Mondrian,” Land & McCann, 1971). Reliable estimation of the color of a matte surface is a difficult if not impossible computational problem in such limited scenes (Maloney, 1999). In more realistic, three-dimensional scenes the difficulty of the problem increases, in part, because the effective illumination incident on the surface (the light field) now depends on surface orientation and location. We review recent work in multiple laboratories that examines (1) the degree to which the human visual system discounts the light field in judging matte surface lightness and color and (2) what illuminant cues the visual system uses in estimating the flow of light in a scene.