The retinal dopaminergic system is a global regulator of retinal function. Apart from the fact that the rates of dopamine synthesis and release are increased by increasing illumination, the visual image parameters that influence dopaminergic function are mostly unknown. Roles for spatial and temporal frequency and image contrast are suggested by the effects of form-deprivation with a diffusing goggle. Form-deprivation reduces the rates of dopamine synthesis and release, and induces myopia, which is prevented by dopamine agonists. Our purpose here was to identify visual stimulus parameters that activate dopaminergic amacrine cells and elicit dopamine release. White Leghorn cockerels 4–7 days old were exposed to 2 h of form-deprivation, reduced light intensity, or stimuli of varied temporal or spatial frequency. Activation of dopaminergic neurons, labeled for tyrosine hydroxylase (TH), was assessed with immunocytochemistry for c-Fos, and dopamine release was measured by HPLC analysis of dopamine metabolite accumulation in the vitreous body. Form-deprivation did not reduce TH+ cell activation or vitreal dopamine metabolite accumulation any more than did neutral-density filters of approximately equal transmittance. TH+ cell activation and vitreal metabolite accumulation were not affected significantly by exposure to 2, 5, 10, 15, or 20 Hz stroboscopic stimulation on a dark background, or by sine-wave gratings of 0.089, 0.44, 0.89, 1.04, or 3.13 cycles/deg compared to a uniform gray target of equal mean luminance. These data indicate that the retinal dopaminergic system does not respond readily to short-term changes in visual stimulus parameters, other than light intensity, under the conditions of these experiments.

Mechanisms underlying the development of the primate area of high acuity (AHA) remain poorly understood. Finite-element models have identified retinal stretch and intraocular pressure (IOP) as possible mechanical forces that can form a pit (Springer & Hendrickson, 2004). A series of Macaca nemestrina monkey retinas between 68 days postconception (dpc) and adult were used to quantify growth and morphological changes. Retinal and pars plana length, optic disc diameter, disc-pit distance, and inner and outer retinal laminar thickness were measured over development to identify when and where IOP or stretch might operate. Horizontal optic disc diameter increased 500 μm between 115 dpc and 2 months after birth when it reached adult diameter. Disc growth mainly influences the immediate surrounding retina, presumably displacing retinal tissue centrifugally. Pars plana elongation also began at 115 dpc and continued steadily to 3–4 years postnatal, so its influence would be relatively constant over retinal development. Unexpectedly, horizontal retinal length showed nonlinear growth, divided into distinct phases. Retinal length increased rapidly until 115 dpc and then remained unchanged (quiescent phase) between 115–180 dpc. After birth, the retina grew rapidly for 3 months and then very slowly into adulthood. The onset of pit development overlapped the late fetal quiescent phase, suggesting that the major mechanical factor initiating pit formation is IOP, not retinal growth-induced stretch. Developmental changes in the thickness of retinal layers were different for inner and outer retina at many, but not all, of the ten eccentricities examined. Peripheral inner and outer retinal layers thinned appreciably with age, consistent with retinal stretch having a larger effect on the retinal periphery. Central inner retina around the area of high acuity (AHA) changed tri-phasically. It increased in thickness prenatally, thinned transiently after birth, and then resumed thickening. Transient postnatal inner retinal thinning around the pit coincided with the resumption of retinal growth and with cone packing providing evidence that a small amount of growth-induced central retinal stretch may account for cone packing as previously hypothesized (Springer, 1999). Central outer retina around the AHA progressively thickened over the fetal period. It reached asymptotic thickness at birth and continued to thicken into adulthood at some temporal, but not nasal, central eccentricities. These data indicate that peripheral outer and inner retina progressively thin with age because of eye growth-induced stretch, while central retina is minimally affected by stretch. Outer and inner retinal laminar thickness at the same locus can change in different directions, suggesting that they shear with respect to one another. This shearing induces the elongation of Henle axons, while their angle reflects the direction of shear.

The conventional view that glucose is the substrate for neuronal energy metabolism has been recently challenged by the “lactate shuttle” hypothesis in which glutamate cycling in glial cells drives all neuronal glucose metabolism. According to this view, glutamate released by activated retinal neurons is transported into Müller (glial) cells where it triggers glycolysis. The lactate released by Müller cells serves as the energy substrate for neuronal metabolism. Because the L-Glutamate/aspartate transporter (GLAST) is the predominant, Na+-dependent, glutamate transporter expressed by Müller cells, we have used GLAST-knockout (GLAST−/−) mice to examine the relationship between lactate release and GLAST activity in the retina. We found that glucose uptake and lactate production by the GLAST−/− mouse retina was similar to that observed in the wild type mouse retina. Furthermore, addition of 1 mM glutamate and NH4Cl to the incubation medium did not further stimulate glucose uptake in either case. When lactate release was measured in the presence of the lactate uptake inhibitor, α-cyano-4-hydroxycinnamate, there was no significant change in the amount of lactate released by retinas from GLAST−/− mice compared to the wild type. Finally, lactate release was similar under both dark and light conditions. These results show that lactate production and release is not altered in retinas of GLAST−/− mice, which suggests that metabolic coupling between photoreceptors and Müller cells is not mediated by the glial glutamate transporter, GLAST.

Gap junctions are commonplace in retina, often between cells of the same morphological type, but sometimes linking different cell types. The strength of coupling between cells derives from the properties of the connexins, but also is regulated by the intracellular environment of each cell. We measured the relative coupling of two different gap junctions made by AII amacrine cells of the rabbit retina. Permeability to the tracer Neurobiotin was measured at different concentrations of the neuromodulators dopamine, nitric oxide, or cyclic adenosine monophosphate (cAMP) analogs. Diffusion coefficients were calculated separately for the gap junctions between pairs of AII amacrine cells and for those connecting AII amacrine cells with ON cone bipolar cells. Increased dopamine caused diffusion rates to decline more rapidly across the AII–AII gap junctions than across the AII–bipolar cell gap junctions. The rate of decline at these sites was well fit by a model proposing that dopamine modulates two independent gates in AII–AII channels, but only a single gate on the AII side of the AII–bipolar channel. However, a membrane-permeant cAMP agonist modulated both types of channel equally. Therefore, the major regulator of channel closure in this network is the local cAMP concentration within each cell, as regulated by dopamine, rather than different cAMP sensitivity of their respective gates. In contrast, nitric oxide preferentially reduced AII–bipolar cell permeabilities. Coupling from AII amacrine cells to the different bipolar cell subtypes was differentially affected by dopamine, indicating that light adaptation acting via dopamine release alters network coupling properties in multiple ways.

Significant variation in absolute dark-adapted thresholds is observed both within and between strains of mice with differing ocular pigmentation levels. Differences in threshold within a single strain are related to the Williams' photostasis effect, that is, photoreceptor rhodopsin levels are dependent upon ambient lighting conditions. To examine threshold differences among strains, we equalized rhodopsin levels by maintaining albino mice (c2J/c2J) at 2 × 10−4 cd/m2 (dim light) and black mice at 2 × 102 cd/m2 (bright light). This resulted in ocular rhodopsin levels for albino mice (albino—dim) of 494 ± 11 pmoles/eye and rhodopsin levels for black mice (black—bright) of 506 ± 25 pmoles/eye. For comparison, rhodopsin levels in black mice maintained in dim light are 586 ± 46 pmoles/eye and 217 ± 46 pmoles/eye in albino mice maintained in bright light. We found similar dark-adapted thresholds (6.38 log cd/m2vs. 6.47 log cd/m2)) in albino and black mice with equivalent rhodopsin determined with a water maze test. This suggests that dark-adapted thresholds are directly related to rhodopsin levels regardless of the level of ocular melanin. The number of photoreceptors, photoreceptor layer thickness, and outer segment length did not differ significantly between albino (dark) and black mice (bright). These results demonstrate that the visual sensitivity defect found in hypopigmented animals is secondary to abnormal rhodopsin regulation and that hypopigmented animals have either an improper input to the photostasis mechanism or that the photostasis mechanism is defective.

This study tests the generality of previously demonstrated rod hue biases (red and blue biases at shorter wavelengths and a green bias at longer wavelengths) that cause the loci of the three spectral unique hues to shift to longer wavelengths. We found rod hue biases for 2-deg targets to be generally similar in magnitude and light-level dependence to those observed for 7.4-deg targets (the size most often studied) when measured at 7-deg eccentricity. The largest effects for both test sizes occurred at the lowest light levels tested, 1 log scotopic troland. All three rod hue biases were found with 0.6-deg targets, but were not reliably measurable at the lowest light levels and were reduced in magnitude and consistency across observers. The largest rod hue biases all occurred at the same scotopic light level, which corresponds to different photopic light levels for the three hue biases, because of differences in photopic and scotopic spectral sensitivity. This suggests that no single photopic light level will produce such large effects for all three rod hue biases. Finally, when the rod influence on a specific unique-hue locus was measured using photopically (rather than scotopically) constant stimuli, rod hue biases were still found but were more variable in magnitude and incidence across observers. We conclude that the rod hue biases we have previously described can be found with smaller stimuli, at somewhat higher light levels, and under photopically constant conditions, although our prior conditions tend to produce larger, more reliable rod hue biases.

The synaptic terminals of mammalian rod bipolar cells are the targets of multiple presynaptic inhibitory inputs arriving from glycinergic and GABAergic amacrine cells. To investigate the contribution of these different inhibitory receptor types, we have applied the patch-clamp technique in acutely isolated slices of the adult mouse retina. By using the whole-cell configuration, we measured and analyzed the spontaneous postsynaptic currents (PSCs) in rod bipolar cells. The spontaneous synaptic activity of rod bipolar cells was very low. However, when amacrine cells were depolarized by AMPA or kainate, the PSC frequency in rod bipolar cells increased significantly. These PSCs comprised several types that could be distinguished by pharmacological and kinetic criteria. Strychnine-sensitive, glycinergic PSCs were characterized by a mean peak amplitude of −43.5 pA and a weighted decay time constant (τw) of 10.9 ms. PSCs that persisted in the presence of strychnine, but were completely inhibited by bicuculline, were mediated by GABAARs. They had a mean peak amplitude of −20.0 pA and a significantly faster τw of 5.8 ms. Few PSCs remained in the presence of strychnine and bicuculline, suggesting that they were mediated by GABACRs. These PSCs were characterized by much smaller amplitudes (−6.2 pA) and a significantly slower decay kinetics (τw = 51.0 ms). We conclude that rod bipolar cells express at least three types of functionally different inhibitory receptors, namely GABAARs, GABACRs, and GlyRs that may ultimately regulate the Ca2+ influx into rod bipolar cell terminals, thereby modulating their glutamate release.

Mammalian retinas receive input from the posterior hypothalamus, and the neurotransmitter in this pathway is histamine. To determine whether histamine influences ganglion cells, we analyzed the effects of histamine on their maintained and light-evoked activity in vitro. In monkeys, histamine increased the maintained firing rate in 42% of ganglion cells, decreased it in 38%, and had no effect in 20%. When histamine and the HR3 agonist, methylhistamine, were applied to the same cells in succession, their effects were sometimes different, a finding suggesting that at least one other histamine receptor is present. In addition, the responses of some ganglion cells to full-field light stimuli were decreased by histamine and methylhistamine. In rats, the effects of histamine were somewhat different. Histamine increased the maintained firing rate of 82% of ganglion cells. Methylhistamine and the HR2 agonist, dimaprit, had the same effects as histamine. In some cells, histamine increased the light responses, but in others it decreased them. Histamine had no effect on ganglion cells in either species when synaptic transmission was blocked by low Ca2+/high Mg2+ Ames medium. Thus, the major effects of histamine were on the maintained activity of retinal ganglion cells. In both rats and monkeys, 80% or more of the ganglion cells were affected by histamine, and these responses were mediated by at least two of the histamine receptor subtypes.

This report describes a second-generation photostimulator with four primary lights that allows independent control of the stimulation of the four receptor types in the human eye. The new design uses LEDs (with light levels controlled by eight drivers that include voltage-to-frequency converters that provide 1-μs pulses at frequencies up to 250 kHz), with four center channels being combined by use of a fiber optic assembly, and likewise for four surround channels. Four fiber optic bundles are merged into a single bundle whose output is fed into a spatial homogenizer terminated by a diffuser. An interference filter is sandwiched between each LED and the fiber optic bundle. Two camera lenses collimate light from the diffusers, one for center and one for surround. The center-surround field configuration is formed by a photometric cube with a mirrored ellipse on the hypotenuse. A field lens places images of the diffusers in the plane of an artificial pupil. The fields are highly uniform. Following alignment and calibration, the center and surround fields are indistinguishable. An observer calibration procedure, designed to compensate for prereceptoral filtering, is shown by calculation to correct also for normal observer receptoral spectral sensitivity variation. With the instrument calibrated for the individual observer, a peripherally fixated 200-ms 40% contrast rod center field pulse, highly conspicuous under dark adaptation, is invisible following light adaptation.

When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.

Numerous reports have concluded that zebrafish (Danio rerio) possesses A1-based visual pigments in their rod and cone photoreceptors. In the present study, we investigated the possibility that zebrafish have a paired visual pigment system. We measured the spectral absorption characteristics of photoreceptors from zebrafish maintained in different temperature regimes and those treated with exogenous thyroid hormone using CCD-based microspectrophotometry. Rods from fish housed at 15°C and 28°C were not significantly different, having λmax values of 503 ± 5 nm (n = 106) and 504 ± 6 nm (n = 88), respectively. Thyroid hormone treatment (held at 28°C), however, significantly shifted the λmax of rods from 503 ± 5 nm (n = 194) to 527 ± 8 nm (n = 212). Cone photoreceptors in fish housed at 28°C (without thyroid hormone treatment) had λmax values of 361 ± 3 nm (n = 2) for ultraviolet-, 411 ± 5 nm (n = 18) for short-, 482 ± 6 nm (n = 9) for medium-, and 565 ± 10 nm (n = 14) for long-wavelength sensitive cones. Thyroid hormone treatment of fish held at 28°C significantly shifted the λmax of long-wavelength sensitive cones to 613 ± 11 nm (n = 20), substantially beyond that of the λmax of the longest possible A1-based visual pigment (∼580 nm). Thyroid hormone treatment produced smaller shifts of λmax in other cone types and increased the half-band width. All shifts in photoreceptor λmax values resulting from thyroid hormone treatment matched predictions for an A1- to A2-based visual pigment system. We therefore conclude that zebrafish possess a rhodopsin–porphyropsin interchange system that functions to spectrally tune rod and cone photoreceptors. We believe that these observations should be carefully considered during analysis of zebrafish spectral sensitivity.

A novel noise-masking technique was used to test D'Zmura and Knoblauch's (1998) idea that subjects employ off-channel looking in detecting chromatic test stimuli embedded in spatiotemporal chromatic noise. Detection thresholds were obtained for stationary, isoluminant, Gaussian-windowed (σx = σy = 2.25 deg; σt = 0.25 s), 135 deg (yellow/blue) or 160 deg (orange/blue–green), sinusoidal test gratings (11 deg × 11 deg; 0.75 cycle/deg) superimposed on each of a series of dynamic, random-check chromatic noise masks varying in azimuth in DKL space. Thresholds for detecting the test in the presence of these variable masks were again measured in the presence of an additional (auxiliary) noise mask created from colors falling on azimuths of 0 deg or 90 deg (135-deg test) or 0 deg or 135 deg (160-deg test). The effectiveness, kvar, of the variable noise masks in elevating grating detection thresholds was determined by fitting the detection data to the Pelli-Legge equation relating test detection energy to variable noise-mask energy: Et = K + kvarNvar. Differences in the calculated values of kvar for detection data obtained with and without the auxiliary masks were consistent with off-channel looking and were well accounted for by a simple model based on the idea that subjects possess a multichannel array of linear chromatic detectors spanning the isoluminant plane of DKL space, and they can choose the channel that has the highest signal-to-noise ratio.

The Publishers for Visual Neuroscience would like to say we are sorry for the errors that appeared on the Table of Contents for Volume 21, Number 5.

We have studied the influence of chromatic adaptation upon the perceived visual position of a test stimulus using a Vernier alignment task. Maximum and minimum offsets in spatial position are generated when the adapting and test stimuli lie on the same and orthogonal axes in MBDKL color space, respectively. When the test stimuli lie on intermediate color axes, the measured positional shifts decrease as a function of the angular separation in color space (φ) from the adapting stimulus. At low stimulus contrasts, these shifts follow a sinusoidal function of φ and exhibit broad chromatic tuning and can be accounted for by a model in which the centroid is extracted from the linear combination of after-image, formed by the adapting stimulus, and the test stimulus. Such linear, broadband behavior is consistent with the response properties of chromatic neurons in the precortical visual pathway. At high contrast, and when adaptation gets closer to the S/(L+M) axis, the tuning functions become narrower and require sinusoids raised to increasingly higher exponents in order to describe the data. This narrowing of chromatic tuning is consistent with the tuning properties of chromatic neurons in the striate cortex, and implies the operation of a nonlinear mechanism in the combination of cone outputs.

We measured the regions of the equiluminant plane that are exploited by observers during a Yes/No detection task. The signal was a 640-ms Gaussian modulation (σt = 160 ms) of a Gaussian spatial patch (σs = 2.4 deg) presented in chromatically bivariate uniform noise. One component of the noise was along the direction axial with the signal in color space, the other perpendicular. Four signal directions were tested: along cardinal LM and S axes and two intermediate directions to which the cardinal axes were equally sensitive. The distribution of noise chromaticities from each trial was correlated with the observers' responses and the presence and absence of the signal to build a classification image of the distribution of chromaticities on which the decision of the observer was based. The images show a narrowly selective peak in the signal direction flanked by regions with a broader selectivity. These results raise the possibility that detection judgments are mediated by both linear and nonlinear mechanisms with peak sensitivities between the cardinal directions.

The spectral properties of chromatic-detection mechanisms were investigated using a noise-masking paradigm. Contrast-detection thresholds were measured for a signal with a Gaussian spatial profile, modulated in the equiluminant plane in the presence of spatial chromatic noise. The noise was distributed within a sector in the equiluminant plane, centered on the signal direction. Each stimulus consisted of two adjacent fields, one of which contained the signal, separated horizontally by a gap with the same average chromaticity as the uniform background. Observers were asked to judge on which side of the central fixation point the signal was displayed via a two-alternative, forced-choice (2AFC) paradigm. Contrast thresholds were measured for four color directions and three sector widths at increasing levels of the average energy of the axial component of the noise. Results show that contrast thresholds are unaffected by the width of the noise sector, as previously found for temporally modulated stimuli (D'Zmura & Knoblauch, 1998). The results are consistent with the existence of spectrally broadband linear-detection mechanisms tuned to the signal color direction and support the hypothesis of the existence of higher-order color mechanisms with sensitivities tuned to intermediate directions in color space.

Previous work (Nagy & Thomas, 2003) showed that signals in different Cardinal color mechanisms could be combined to facilitate search for a color target. Further investigation (Nagy et al., 2003) suggested that signals in one Cardinal color mechanism were used to select a subset of stimuli to be attended, while signals in second Cardinal mechanism were used to discriminate the stimuli within the selected subset. In the studies described below, we asked if observers could use color mechanisms tuned to directions other than the Cardinal directions to select and discriminate stimuli. Observers searched for a single target stimulus that differed in chromaticity from nine distractor stimuli. A two-alternative forced-choice procedure was used to estimate thresholds. Results were consistent with the hypothesis that color mechanisms tuned to many different directions in color space mediate discrimination, but suggest that only signals in Cardinal mechanisms can be used to select stimuli for attention.

Results imply that the selection of stimuli for attention on the basis of color may be mediated at the level of the lateral geniculate nucleus (LGN).

The optical density of the human crystalline lens progressively increases with age, the greatest increase in the visible spectrum being at short wavelengths. This produces a gradual shift in the spectral distribution of the light reaching the retina, yet color appearance remains relatively stable across the life span, implying that the visual system adapts to compensate for changes in spectral sensitivity. We explored properties of this adaptive renormalization by measuring changes in color appearance following cataract surgery. When the lens is removed, cataract patients often report a large perceptual shift in color appearance that can last for months. This change in color appearance was quantified for four cataract patients (63–84 years) by determining the chromaticity of stimuli that appeared achromatic before surgery, and at various intervals after surgery for up to 1 year. Stimuli were presented on a calibrated CRT as 9.5-deg spots, with 3-s duration and 3-s interstimulus intervals (ISIs). Chromaticity was adjusted by the subjects in CIE L*a*b* color space with luminance fixed at 32 cd/m2, on a dark background. We also estimated the optical density of the cataractous lens by comparing absolute scotopic thresholds from 410 nm to 600 nm before and after surgery. The results demonstrated that immediately following surgery there is a large increase in the short-wave light reaching the retina, mainly below 500 nm. The achromatic settings generally showed an initial large shift in the “yellow” direction after surgery that gradually (but never fully) returned to the original achromatic point before surgery. The shifts in the achromatic point occur over a number of months and appear to occur independently of the fellow eye.

If the relative phase of red and green modulated lights is changed, at low temporal frequencies the response of cells of the magnocellular (MC) pathway has been found to be minimal not to counterphase, chromatic modulation (as expected of a luminance mechanism) but shifted to some phase intermediate between luminance and chromatic modulation. The results could only be modeled by assuming interaction between achromatic and chromatic inputs to MC cells. The ‘phase shift’ resembled that seen with psychophysical threshold measurements using the same stimuli. Psychophysical results also showed that the phase shift is dependent on the chromaticity of a background. The results reported here show that the direction of the phase shift in MC cells is reversed by changing the background from long to short wavelengths and is consistent with psychophysical observations. Cell behavior was again modeled by assuming vector summation of achromatic and chromatic inputs. The reversal of phase-shift direction requires a reversal in polarity of the chromatic input. The underlying physiological mechanism may involve summation of chromatic signals of opposite polarity; if the relative size of these signals depends on the background, this may determine the direction of phase shift.

Vernier thresholds are determined by luminance rather than chromatic contrast when both are present in vernier targets. The role of luminance and chromatic mechanisms in vernier performance under equiluminant conditions remains uncertain. Temporal summation functions for vernier thresholds with luminance and red–green equiluminant gratings were compared to those for detection thresholds with similar stimuli. Vernier thresholds showed similar temporal summation for luminance and chromatic gratings, which is consistent with a single mechanism underlying vernier performance in the two conditions. However, detection thresholds showed a shorter temporal summation duration for luminance gratings than for chromatic gratings, which suggests that two different mechanisms underlie detection thresholds. Analysis of physiological data supports the hypothesis that the frequency-doubled response of ganglion cells in the magnocellular pathway can provide accurate spatiotemporal information for vernier performance at equiluminance.