To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of ≈35 vesicles/ribbon-style active zone. Following depletion, this pool was refilled with a time constant of ≈7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time constant that ranged from 2 to 21 s depending on the magnitude of the preceding Ca2+ transient. In addition, a brief, calcium-dependent delay often preceded the start of onset of membrane recovery. Thus, several aspects of synaptic vesicle dynamics appear to be conserved between rod-dominant bipolar cells of fish and mammalian rod bipolar cells. A major difference is that the number of vesicles available for release is significantly smaller in the mouse rod bipolar cell, both as a function of the total number per neuron and on a per active zone basis.

The 19th Symposium of the International Colour Vision Society (ICVS) was held in Belém, Brazil in July 2007. This was the first time that the Society has met in Latin America. The Amazonian region was a unique location for this inauguration due both to its situation close to a vast, largely unexplored region of nature, and resources—an inspiring challenge for scientific study—and to the quality of the vision research developing in the region.

Your journal enters its third decade with the publication of this issue. The first volume, published in 1988, appeared in quarterly issues, but moved to bi-monthly production in 1989, and then monthly release from 1990 through 1992. Two volumes appeared each year during 1989–1992, accounting for the fact that this twenty-first year coincides with volume 25. In 1993, it returned to bi-monthly publication, remaining so for the past 15 years. During this period, other vision-related journals have made their debut, but Visual Neuroscience remains a premier venue for publishing fundamental research in the neurobiology of vision.

Thirty years ago virtually everything known about primate color vision derived from psychophysical studies of normal and color-defective humans and from physiological investigations of the visual system of the macaque monkey, the most popular of human surrogates for this purpose. The years since have witnessed much progress toward the goal of understanding this remarkable feature of primate vision. Among many advances, investigations focused on naturally occurring variations in color vision in a wide range of nonhuman primate species have proven to be particularly valuable. Results from such studies have been central to our expanding understanding of the interrelationships between opsin genes, cone photopigments, neural organization, and color vision. This work is also yielding valuable insights into the evolution of color vision.

The Na-K-2Cl cotransporter (NKCC) is a Cl− uptake transporter that is responsible for maintaining a Cl− equilibrium potential positive to the resting potential in neurons. If NKCC is active, GABA and glycine can depolarize neurons. In view of the abundance of GABAergic and glycinergic synapses in retina, we undertook a series of studies using immunocytochemical techniques to determine the distribution of NKCC in retinas of both developing and adult mice. We found NKCC antibody (T4) labeling present in retinas from wild-type mice, but not in NKCC1-deficient mice, suggesting that the NKCC1 subtype is a major Cl− uptake transporter in mouse retina. Strong labeling of NKCC1 was present in horizontal cells and rod-bipolar dendrites in adult mice. Interestingly, we also found that a diffuse labeling pattern was present in photoreceptor terminals. However, NKCC1 was barely detectable in the inner retina of adult mice. Using an antibody against K-Cl cotransporter 2 (KCC2), we found that KCC2, a transporter that extrudes Cl−, was primarily expressed in the inner retina. The expression of NKCC1 in developing mouse retinas was studied from postnatal day (P) 1 to P21, NKCC1 labeling first appeared in the dendrites of horizontal and rod-bipolar cells as early as P7, followed by photoreceptor terminals between P10-P14; with expression gradually increasing concomitantly with the growth of synaptic terminals and dendrites throughout retinal development. In the inner retina, NKCC1 labeling was initially observed in the inner plexiform layer at P1, but labeling diminished after P5. The developmental increase in NKCC expression only occurred in the outer retina. Our results suggest that the distal synapses and synaptogenesis in mouse retinas undergo a unique process with a high intracellular Cl− presence due to NKCC1 expression.

Neural models of retinal processing provide an important tool for analyzing retinal signals and their functional significance. However, it is here argued that in biological reality, retinal connectivity is unlikely to be as specific as ideal neural models might suggest. The retina is thought to provide functionally specific signals, but this specificity is unlikely to be anatomically complete. This is illustrated by examples of cone connectivity to macaque ganglion cells. For example, cells of the magnocellular pathway appear to avoid short-wavelength cone input, so that such input is negligible under normal conditions. However, there is anatomical, physiological, and psychophysical evidence that under special conditions, weak input may be revealed. Second, ideal models of how retinal information is centrally utilized have to take into account the biological reality of retinal signals. The stochastic nature of impulse trains modifies signal-to-noise ratio in unexpected ways. Also, non-linearities in cell responses make, for example, multiplexing of luminance and chromatic signals in the parvocellular pathway impracticable. The purpose of this analysis is to show than ideal neural models must confront an often more complex and nuanced physiological reality.

This study examined the effectiveness with which motion parallax information can be utilized by rhesus monkeys for depth perception. A visual display comprised of random-dots that mimicked a rigid, three-dimensional object rocking back and forth was used. Differential depth was produced by presenting sub-regions of the dots moving at different velocities from the rest of dots in the display. The tasks for the monkeys were to detect or discriminate a target region that was protruding the furthest from the background plane. To understand the role of stimulus movement, we examined the accuracy and the rapidity of the saccadic responses as a function of rocking velocity of the entire three-dimensional object. The results showed that performance accuracy improved and reaction times decreased with increasing rocking velocities. The monkeys can process the motion parallax information with remarkable rapidity such that the average reaction time ranged between 212 and 246 milliseconds. The data collected suggest that the successive activation of just two sets of cones is sufficient to perform the task.

The melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer retinal pathology (15 weeks of age). In particular, these cells express βIII tubulin, α-acetylated tubulin, and microtubule-associated proteins (MAPs), while remaining negative for other RGC markers such as neurofilaments, calretinin, and parvalbumin. By 14 months of age, melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve vascular remodeling). The morphological abnormalities in melanopsin processes are associated with elevated immunoreactivity for MAP1b and a reduction in α-acetylated tubulin. Quantification of ipRGCs in whole mounts reveals reduced melanopsin cell number with increasing age. Focusing on the retinal periphery, we find a significant decline in melanopsin cell density contrasted by a stability of melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of melanopsin processes in the far peripheral retina, a structure that is coincident with a short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve vascular remodeling. However, a significant number of melanopsin positive cells survive into advanced stages of retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human retinal disease in order to preserve integrity of the inner retinal photoreceptive network.

Two groups of retinal cone bipolar cells (CBCs) in rats were found to express voltage-gated Na+ channels. The axon terminals of the first group stratify in sublamina 2 of the inner plexiform layer (IPL) and partially overlap with the OFF-cholinergic band. This group was identified as type 3 CBCs. The axon terminals of the second group stratify in sublamina 3 of the IPL, slightly distal to the ON-cholinergic band. Cells of this second group resemble type 5 CBCs. In addition, we observed another group of ON-type CBCs with terminal stratification similar to that of the second group. However, this latter group did not show any Na+ current, instead exhibiting a large hyperpolarization-activated cyclic nucleotide-gated cation current, suggesting the existence of two subclasses of physiologically distinct type 5 CBCs. Both groups of Na+-expressing bipolar cells were capable of generating a rapid tetrodotoxin-sensitive action potential as revealed by current injection. Multiple spike-like potentials were also observed in some of these cells. Results of this study provide valuable insights into the function of voltage-gated Na+ channels of retinal bipolar cells in retinal processing.

Action potentials were recorded from rat retinal ganglion cell fibers in the presence of a uniform field, and the maintained discharge pattern was characterized. Spike trains recorded under ketamine–xylazine anesthesia were generally stationary, while those recorded under urethane anesthesia often showed slow, undriven, quasiperiodic fluctuations in firing rate. In light of these nonstationarities, interspike interval distributions and power spectral densities are reported for data collected primarily under ketamine–xylazine. The majority of cells had multimodal interval distributions, with the first peak in the range of 25.0–38.5 ms and the subsequent peaks occurring at integer multiples of the first peak. Cells with unimodal distributions were fit well by a gamma distribution function. Interval and spike count statistics showed that ON cells tended to fire faster than OFF cells and that cells with higher rates fired in a more regular manner, with the coefficient of variation covering a wide range of values across all cells (0.43–0.97). Both ON and OFF cells show serial correlations between adjacent interspike intervals, while ON cells also showed second-order correlations. Cells with multimodal interval distribution showed a strong peak at high frequencies in the power spectra in the range of 28.9–41.4 Hz. Oscillations were present under both anesthetic conditions and persisted in the dark at a slightly lower frequency, implying that the oscillations are generated independent of any light stimulus but can be modulated by light level. The oscillation frequency varied slightly between cells of the same type and in the same eye, suggesting that multiple oscillatory generating mechanisms exist within the retina. Cells with high-frequency oscillations were described well by an integrate-and-fire model with the input consisting of Gaussian noise plus a sinusoid where the phase was jittered randomly to account for the bandwidth present in the oscillations.

To refine inhibitory circuitry models for ON and OFF pathways in zebrafish retina, GABAergic properties of zebrafish bipolar cells were studied with two techniques: whole cell patch responses to GABA puffs in retinal slice, and voltage probe responses in isolated cells. Retinal slices documented predominantly axon terminal responses; isolated cells revealed mainly soma-dendritic responses. In the slice, GABA elicited a conductance increase, GABA responses were more robust at axon terminals than dendrites, and Erev varied with [Cl−]in. Axon terminals of ON- and OFF-type cells were similarly sensitive to GABA (30–40 pA peak current); axotomized cells were unresponsive. Bicuculline-sensitive, picrotoxin-sensitive, and picrotoxin-insensitive components were identified. Muscimol was as effective as GABA; baclofen was ineffective. Isolated bipolar cells were either intact or axotomized. Even in cells without an axon, GABA or muscimol (but not baclofen) hyperpolarized dendritic and somatic regions, suggesting significant distal expression. Median fluorescence change for GABA was −0.22 log units (∼ −16 mV); median half-amplitude dose was 0.4 μM. Reduced [Cl−]out blocked GABA responses. GABA hyperpolarized isolated ON-bipolar cells; OFF-cells were either unresponsive or depolarized. Hyperpolarizing GABA responses in isolated cells were bicuculline and TPMPA insensitive, but blocked or partially blocked by picrotoxin or zinc. In summary, axon terminals contain bicuculline-sensitive GABAA receptors and both picrotoxin-sensitive and insensitive GABAC receptors. Dendritic processes express zinc- and picrotoxin-sensitive GABAC receptors.

The posterior cingulate cortex (PCC) is involved in higher order sensory and sensory-motor integration while the planum temporale/parietal operculum (PT/PO) junction takes part in auditory motion and vestibular processing. Both regions are activated during different types of visual stimulation. Here, we describe the response characteristics of the PCC and PT/PO to basic types of visual motion stimuli of different complexity (complex and simple coherent as well as incoherent motion). Functional magnetic resonance imaging (fMRI) was performed in 10 healthy subjects at 3 Tesla, whereby different moving dot stimuli (vertical, horizontal, rotational, radial, and random) were contrasted against a static dot pattern. All motion stimuli activated a distributed cortical network, including previously described motion-sensitive striate and extrastriate visual areas. Bilateral activations in the dorsal region of the PCC (dPCC) were evoked using coherent motion stimuli, irrespective of motion direction (vertical, horizontal, rotational, radial) with increasing activity and with higher complexity of the stimulus. In contrast, the PT/PO responded equally well to all of the different coherent motion types. Incoherent (random) motion yielded significantly less activation both in the dPCC and in the PT/PO area. These results suggest that the dPCC and the PT/PO take part in the processing of basic types of visual motion. However, in dPCC a possible effect of attentional modulation resulting in the higher activity evoked by the complex stimuli should also be considered. Further studies are warranted to incorporate these regions into the current model of the cortical motion processing network.

Five lagged cells were recognized by extracellular recording in the lateral geniculate nucleus of an awake, behaving macaque monkey. Previous reports of lagged cells were all in the anesthetized cat. Both parvocellular and magnocellular lagged cells were observed. Response timing was distributed continuously across the population, and both sustained and transient responses were seen in the magnocellular subpopulation. Cortex thus receives signals with a wide range of timing, which can mediate direction selectivity across multiple dimensions.

The topographic analysis of retinal ganglion and photoreceptor cell distributions yields valuable information for assessing the visual capabilities and behavioral ecology of vertebrates. This study examines whole-mounted retinas of four elasmobranch species, the ornate wobbegong, Orectolobus ornatus; the whitetip reef shark, Triaenodon obesus; the epaulette shark, Hemiscyllium ocellatum; and the east Australia shovelnose ray, Aptychotrema rostrata, for regional specializations mediating zones of improved visual ability. These species represent a range of lifestyles: benthic, mid-water, diurnal, and nocturnal. Both photoreceptors (visualized using differential interference contrast optics) and ganglion cells (stained with cresyl violet) in the retina are extensively sampled, and their spatial distribution is found to be nonuniform, exhibiting areae or “visual streaks.” In general, the topographic distributions of both cell populations are in register and match well with respect to the location of regions of high density. However, the location of peaks in rod and cone densities can vary within a retina, indicating that preferential sampling of different regions of the visual field may occur in photopic and scotopic vision. Anatomical measures of the optical limits of resolving power, indicated by intercone spacing, range from 3.8 to 13.1 cycles/deg. Spatial limits of resolving power, calculated from ganglion cell spacing, range from 2.6 to 4.3 cycles/deg. Summation ratios, assessed by direct comparison of cell densities of photoreceptors (input cells) and ganglion cells (output cells), at more than 150 different loci across the retina, show topographic differences in signal convergence (ranging from 25:1 to over 70:1). Species-specific retinal specializations strongly correlate to the habitat and feeding behavior of each species.

Electrophysiological and molecular genetic studies have shown that howler monkeys (Alouatta) are unique among all studied platyrrhines: they have the potential to display trichromatic color vision among males and females. This study examined the color discrimination abilities of four howler monkeys (Alouatta caraya) through a series of tasks involving a behavioral paradigm of discrimination learning. The animals were maintained and housed as a group in the Zoological Gardens of Brasília and were tested in their own home cages. Stimuli consisting of pairs of Munsell color chips were presented in random brightness values to assure that discriminations were based on color rather than brightness cues. All the animals (three males, one female) successfully discriminated all the stimulus pairs, including those that would be expected to be difficult for a dichromatic monkey. These results are consistent with the earlier predictions suggesting that howler monkeys are routinely trichromatic.

The present paper describes the results of architectural and electrophysiological mapping observations of the medial bank of the suprasylvian sulcus of the ferret immediately caudal to somatosensory regions. The aim was to determine if the ferret possessed a homologous cortical area to the anteromedial lateral suprasylvian visual area (AMLS) of the domestic cat. We studied the architectural features and visuotopic organization of a region that we now consider to be a homologue to the cat AMLS. This area showed a distinct architecture and retinotopic organization. The retinotopic map was complex in nature with a bias towards representation of the lower visual field. These features indicate that the region described here as AMLS in the ferret is indeed a direct homologue of the previously described cat AMLS and forms part of a hierarchy of cortical areas processing motion in the ferret visual cortex. With the results of the present study and those of earlier studies a total of twelve cortical visual areas have been determined presently for the ferret, all of which appear to have direct homologues with visual cortical areas in the cat (which has a total of eighteen areas).

GABA-mediated interactions between horizontal cells (HCs) and bipolar cells (BCs) transform signals within the image-processing circuitry of distal retina. To further understand this process, we have studied the GABA-driven membrane responses from isolated retinal neurons. Papain-dissociated retinal cells from adult zebrafish were exposed to GABAergic ligands while transmembrane potentials were monitored with a fluorescent voltage-sensitive dye (oxonol, DiBaC4(5)). In HCs hyperpolarizing, ionotropic GABA responses were almost never seen, nor were responses to baclofen or glycine. A GABA-induced depolarization followed by after hyperpolarization (dep/AHP) occurred in 38% of HCs. The median fluorescence increase (dep component) was 0.17 log units, about 22 mV. HC dep/AHP was not blocked by bicuculline or picrotoxin. Muscimol rarely evoked dep/AHP responses. In BCs picrotoxin sensitive, hyperpolarizing, ionotropic GABA and muscimol responses occurred in most cells. A picrotoxin insensitive dep/AHP response was seen in about 5% of BCs. The median fluorescence increase (dep component) was 0.18 log units, about 23 mV. Some BCs expressed both muscimol-induced hyperpolarizations and GABA-induced dep/AHP responses. For all cells, the pooled Hill fit to median dep amplitudes, in response to treatments with a GABA concentration series, gave an apparent k of 0.61 μM and an n of 1.1. The dep/AHP responses of all cells required both extracellular Na+ and Cl−, as dep/AHP was blocked reversibly by Li+ substituted for Na+ and irreversibly by isethionate substituted for Cl−. All cells with dep/AHP responses in zebrafish have the membrane physiology of neurons expressing GABA transporters. These cells likely accumulate GABA, a characteristic of GABAergic neurons. We suggest Na+ drives GABA into these cells, depolarizing the plasma membrane and triggering Na+, K+-dependent ATPase. The ATPase activity generates AHP. In addition to a GABA clearance function, these large-amplitude transporter responses may provide an outer plexiform layer GABA sensor mechanism.

During their complex life history, anguilliform eels go through a major metamorphosis when developing from a fresh water yellow eel into a deep-sea silver eel. In addition to major changes in body morphology, the visual system also adapts from a fresh water teleost duplex retina with rods and cones, to a specialized deep-sea retina containing only rods. The history of the rods is well documented with an initial switch from a porphyropsin to a rhodopsin (P5232 to P5011) and then a total change in gene expression with the down regulation of a “freshwater” opsin and its concomitant replacement by the expression of a typical “deep-sea” opsin (P5011 to P4821). Yellow eels possess only two spectral classes of single cones, one sensitive in the green presumably expressing an RH2 opsin gene and the second sensitive in the blue expressing an SWS2 opsin gene. In immature glass eels, entering into rivers from the sea, the cones contain mixtures of rhodopsins and porphyropsins, whereas the fully freshwater yellow eels have cone pigments that are almost pure porphyropsins with peak sensitivities at about 540–545 nm and 435–440 nm, respectively. However, during the early stages of metamorphosis, the pigments switch to rhodopsins with the maximum sensitivity of the “green”-sensitive cone shifting to about 525 nm, somewhat paralleling, but preceding the change in rods. During metamorphosis, the cones are almost completely lost.

In this study, we examined procedures that alter saccadic latencies and target selection to visual stimuli and electrical stimulation of area V1 in the monkey. It has been shown that saccadic eye movement latencies to singly presented visual targets form a bimodal distribution when the fixation spot is turned off a number of milliseconds prior to the appearance of the target (the gap period); the first mode has been termed express saccades and the second regular saccades. When the termination of the fixation spot is coincident with the appearance of the target (0 ms gap), express saccades are rarely generated. We show here that a bimodal distribution of saccadic latencies can also be obtained when an array of visual stimuli is presented prior to the appearance of the visual target, provided the elements of the array overlap spatially with the visual target. The overall latency of the saccadic eye movements elicited by electrical stimulation of area V1 is significantly shortened both when a gap is introduced between the termination of the fixation spot and the stimulation and when an array is presented. However, under these conditions, the distribution of saccadic latencies is unimodal. When two visual targets are presented after the fixation spot, introducing a gap has no effect on which target is chosen. By contrast, when electrical stimulation is paired with a visual target, introducing a gap greatly increases the frequency with which the electrical stimulation site is chosen.

A 4 base pair deletion in a splice donor site of the Mfrp (membrane-type frizzled-related protein) gene, herein referred to as Mfrprd6/rd6, is predicted to lead to the skipping of exon 4 and photoreceptor degeneration in retinal degeneration 6 (rd6) mutant mice. Little, however, is known about the function of the protein or how the mutation causes the degenerative retinal phenotype. Here we examine ultrastructural changes in the retina of Mfrprd6/rd6 mice to determine the earliest effects of the mutation. We also extend the reported observations of the expression pattern of the dicistronic Mfrp/C1qtnf5 message and the localization of these and other retinal pigment epithelium (RPE) and retinal proteins during development and assess the ability of RPE cells to phagocytize outer segments (OSs) in mutant and wild-type (WT) mice. At the ultrastructural level, OSs do not develop normally in Mfrprd6/rd6 mutants. They are disorganized and become progressively shorter as mutant mice age. Additionally, there are focal areas in which there is a reduction of apical RPE microvilli. At P25, the rod electroretinogram (ERG) a-wave of Mfrprd6/rd6 mice is reduced in amplitude by ~50% as are ERG components generated by the RPE. Examination of β-catenin localization and Fos and Tcf-1 expression, intermediates of the canonical Wnt pathway, showed that they were not different between mutant and WT mice, suggesting that MFRP may operate through an alternative pathway. Finally, impaired OS phagocytosis was observed in Mfrprd6/rd6 mice both in standard ambient lighting conditions and with bright light exposure when compared to WT controls.