The response amplitude of cat striate cortical cells is usually reduced after exposure to high-contrast stimuli. The temporal characteristics and contrast sensitivity of this phenomenon were explored by stimulating cortical cells with drifting gratings in which contrast sequentially incremented and decremented in stepwise fashion over time. All responses showed a clear hysteresis, in which contrast gain dropped on average 0.36 log unit and then returned to baseline values within 60 s. Noticeable gain adjustments were seen in as little as 3 s and with peak contrasts as low as 3%. Contrast adaptation was absent in responses from LGN cells. Adaptation was found to depend on temporal frequency of stimulation, with greater and more rapid adaptation at higher temporal frequencies. Two different tests showed that the mechanism controlling response reduction was influenced primarily by stimulus contrast rather than response amplitude. These results support the existence of a rapid and sensitive cortically based system that normalizes the output of cortical cells as a function of local mean contrast. Control of the adaptation appears to arise at least in part across a population of cells, which is consistent with the idea that the gain control serves to limit the information converging from many cells onto subsequent processing areas.

Primate retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus (M) are much more sensitive to luminance contrast than those ganglion cells projecting to the parvocellular layers (P). We now report that increasing contrast modifies the temporal-frequency response of M cells, but not of P cells. With rising contrast, the M cells' responses to sinusoidal stimuli show an increasing attenuation at low temporal frequencies while the P cells' responses scale uniformly. The characteristic features of M-cell dynamics are well described by a model originally developed for the X and Y cells of the cat, where the hypothesized nonlinear feedback mechanism responsible for this behavior has been termed the contrast gain control (Shapley & Victor, 1978, 1981; Victor, 1987, 1988). These data provide further physiological evidence that the M-cell pathway differs from the P-cell pathway with regard to the functional elements in the retina. Furthermore, the similarity in dynamics between primate M cells and cat X and Y retinal ganglion cells suggests the possibility that P cells, being different from either group, are a primate specialization not found in the retinae of lower mammals.

The effects of V4, MT, and combined V4+MT lesions were assessed on a broad range of visual capacities that included measures of contrast sensitivity, wavelength and brightness discrimination, form vision, pattern vision, motion and flicker perception, stereopsis, and the selection of stimuli that were less prominent than those with which they appeared in stimulus arrays. The major deficit observed was a loss in the ability, after V4 lesions, to select such less prominent stimuli; this was the case irrespective of the manner in which the stimulus arrays were made visible, using either luminance, chrominance, motion, or stereoscopic depth as surface media. In addition, V4 lesions yielded mild deficits in color, brightness, and form vision whereas MT lesions yielded mild to moderate deficits in motion and flicker perception. Both lesions produced mild deficits in contrast sensitivity, shape-from-motion perception, and yielded increased reaction times on many of the tasks. The impairment resulting from combined V4 and MT lesions was not greater than the sum of the deficits of either lesion. None of the lesions produced significant deficits in stereopsis. The findings suggest that (1) area V4 is part of a neural system that is involved in extracting stimuli from the visual scene that elicit less neural activity early in the visual system than do other stimuli with which they appear and (2) several other extrastriate regions and more than just two major cortical processing streams contribute to the processing of basic visual functions in the extrastriate cortex.

Thalamic relay cells fire in two distinct modes, burst or tonic, and the operative mode is dictated by the inactivation state of low-threshold, voltage-gated, transient (or T-type) Ca2+ channels. Tonic firing is seen when the T channels are inactivated via membrane depolarization, and burst firing is seen when the T channels are activated from a hyperpolarized state. These response modes have very different effects on the relay of information to the cortex. It had been thought that only tonic firing is seen in the awake, alert animal, but recent evidence from several species suggests that bursting may also occur. We have begun to explore this issue in macaque monkeys by recording from thalamic relay cells of unanesthetized, behaving animals. In the lateral geniculate nucleus, the thalamic relay for retinal information, we found that tonic mode dominated responses both during alert behavior as well as during sleep. We nonetheless found burst firing present during the vigilant, waking state. There was, however, considerably more burst mode firing during sleep than wakefulness. Surprisingly, we did not find the bursting during sleep to be rhythmic. We also recorded from relay cells of the somatosensory thalamus. Interestingly, not only did these somatosensory neurons exhibit much more burst mode activity than did geniculate cells, but bursting during sleep was highly rhythmic. It thus appears that the level and nature of relay cell bursting may not be constant across all thalamic nuclei.

The ocular-following responses elicited by brief unexpected movements of the visual scene were studied in human subjects. Response latencies varied with the type of stimulus and decreased systematically with increasing stimulus speed but, unlike those of monkeys, were not solely determined by the temporal frequency generated by sine-wave stimuli. Minimum latencies (70–75 ms) were considerably shorter than those reported for other visually driven eye movements. The magnitude of the responses to sine-wave stimuli changed markedly with stimulus speed and only slightly with spatial frequency over the ranges used. When normalized with respect to spatial frequency, all responses shared the same dependence on temporal frequency (band-pass characteristics with a peak at 16 Hz), indicating that temporal frequency, rather than speed per se, was the limiting factor over the entire range examined. This suggests that the underlying motion detectors respond to the local changes in luminance associated with the motion of the scene. Movements of the scene in the immediate wake of a saccadic eye movement were on average twice as effective as movements 600 ms later: post-saccadic enhancement. Less enhancement was seen in the wake of saccade-like shifts of the scene, which themselves elicited weak ocular following, something not seen in the wake of real saccades. We suggest that there are central mechanisms that, on the one hand, prevent the ocular-following system from tracking the visual disturbances created by saccades but, on the other, promote tracking of any subsequent disturbance and thereby help to suppress post-saccadic drift. Partitioning the visual scene into central and peripheral regions revealed that motion in the periphery can exert a weak modulatory influence on ocular-following responses resulting from motion at the center. We suggest that this may help the moving observer to stabilize his/her eyes on nearby stationary objects.

This paper presents results from psychophysical experiments on human binocular rivalry in central and peripheral vision. Results show that the incidence of periods of exclusive visibility of a given eye's rival target increased with decreasing target size, and for a given sized target exclusive visibility increased with retinal eccentricity. Control measures confirmed that these results were not attributable solely to reduced peripheral acuity, to Troxler's effect, or to spatial frequency. We computed the minimum-sized stimulus that would lead to a criterion level of exclusive visibility of one or the other eye; this we term the spatial zone of binocular rivalry. The change in estimated size of spatial zones of rivalry with eccentricity compares favorably with estimates of human cortical magnification. We propose a model that assumes concentrically organized zones of rivalry. These zones do not function independently, but instead exhibit a high degree of mutual excitatory cooperativity. The model has multiple solutions for the foveal zone size, but the best fits predict a diameter of 5.3 or 7.3 min of visual angle; these values dovetail nicely with our empirical estimates of the foveal zone size.

The eyes of growing chicks adjust to correct for myopia (eye relatively long for the focal length of its optics) or hyperopia (eye relatively short for the focal length of its optics). Eyes made functionally hyperopic with negative spectacle lenses become myopic and long, whereas eyes made functionally myopic with positive spectacle lenses become hyperopic and short. We report here that these compensatory growth adjustments occur not only in normal eyes but also in eyes unable to accommodate (focus) because of lesions to the Edinger-Westphal nuclei. Thus, at least in chicks, accommodation is not necessary for growth that reduces refractive errors during development, and may not be necessary for the normal control of eye growth.

To investigate the subcortical connections of the object vision and spatial vision cortical processing pathways, we injected the inferior temporal and posterior parietal cortex of six Rhesus monkeys with retrograde or anterograde tracers. The temporal injections included area TE on the lateral surface of the hemisphere and adjacent portions of area TEO. The parietal injections covered the posterior bank of the intraparietal sulcus, including areas VIP and LIP. Our results indicate that several structures project to both the temporal and parietal cortex, including the medial and lateral pulvinar, claustrum, and nucleus basalis. However, the cells in both the pulvinar and claustrum that project to the two systems are mainly located in different parts of those structures, as are the terminals which arise from the temporal and parietal cortex. Likewise, the projections from the temporal and parietal cortex to the caudate nucleus and putamen are largely segregated. Finally, we found projections to the pons and superior colliculus from parietal but not temporal cortex, whereas we found the lateral basal and medial basal nuclei of the amygdala to be reciprocally connected with temporal but not parietal cortex. Thus, the results show that, like the cortical connections of the two visual processing systems, the subcortical connections are remarkably segregated.

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.

A countermanding paradigm was utilized to investigate the regulation of saccade initiation. Two rhesus monkeys were instructed to generate a saccade to a peripheral target; however, on a fraction of trials after a delay, the monkeys were signaled to inhibit saccade initiation. With short delays between the presentation of the target and the signal to inhibit saccade generation, monkeys withheld saccades to the peripheral target. As the delay of the stop signal increased, monkeys increasingly failed to withhold the saccade. The hypothesis that the generation of the saccade is determined by a race between a go and a stop process provides three explicit means of estimating the covert latency of response to the stop signal. This latency, known as stop signal reaction time, was estimated to be on average 82 ms for both monkeys. Because the stop signal latency represents the time required to exert inhibitory control over saccade production, the countermanding paradigm will be useful for studying neural mechanisms that regulate saccade initiation.

The responses of monkey retinal ganglion cells to sinusoidal stimuli of various temporal frequencies were measured and analyzed at a number of mean light levels. Temporal modulation tuning functions (TMTFs) were measured at each mean level by varying the drift rate of a sine-wave grating of fixed spatial frequency and contrast. The changes seen in ganglion cell temporal responses with changes in adaptation state were similar to those observed in human subjects and in turtle horizontal cells and cones tested with sinusoidally flickering stimuli; “Weber's Law” behavior was seen at low temporal frequencies but not at higher temporal frequencies. Temporal responses were analyzed in two ways: (1) at each light level, the TMTFs were fit by a model consisting of a cascade of low- and high-pass filters; (2) the family of TMTFs collected over a range of light levels for a given cell was fit by a linear negative feedback model in which the gain of the feedback was proportional to the mean light level. Analysis (1) revealed that the temporal responses of one class of monkey ganglion cells (M cells) were more phasic at both photopic and mesopic light levels than the responses of P ganglion cells. In analysis (2), the linear negative feedback model accounted reasonably well for changes in gain and dynamics seen in three P cells and one M cell. From the feedback model, it was possible to estimate the light level at which the dark-adapted gain of the cone pathways in the primate retina fell by a factor of two. This value was two to three orders of magnitude lower than the value estimated from recordings of isolated monkey cones. Thus, while a model which includes a single stage of negative feedback can account for the changes in gain and dynamics associated with light adaptation in the photopic and mesopic ranges of vision, the underlying physical mechanisms are unknown and may involve elements in the primate retina other than the cone.

The oculomotor system has long been thought to rely on an accurate representation of eye displacement or position in a successful attempt to reconcile a stationary target's retinal instability (caused by motion of the eyes) with its corresponding spatial invariance. This is in stark contrast to perceptual localization, which has been shown to rely on a sluggish representation of eye displacement, achieving only partial compensation for the retinal displacement caused by saccadic eye movements. Recent studies, however, have begun to cast doubt on the belief that the oculomotor system posseses a signal of eye displacement superior to that of the perceptual system. To verify this, five humans and one monkey (Macaca nemesthna) served as subjects in this study of oculomotor localization abilities. Subjects were instructed to make eye movements, as accurately as possible, to the locations of three successive visual stimuli. Presentation of the third stimulus (2-ms duration) was timed so that it fell before, during, or after the subject's saccade from the first stimulus to the second. Localization errors in each subject (human and nonhuman) were consistent with the hypothesis that the oculomotor system has access to only a damped representation of eye displacement —a representation similar to that found in perceptual localization studies.

Several neurophysiological studies have shown that the visual cerebral cortex of macaque monkeys performing delayed match-to-sample tasks contains individual neurons whose levels of activity depend on the sample the animal is required to remember. Haenny et al. (1988) reported that the activity of neurons in area V4 of monkeys performing an orientation matching task depends on the orientation for which the animal is searching. It was proposed that these neurons contribute to a representation of the orientation being sought.

We have further characterized these neurons by recording visual responses from individual neurons during multiple behavioral tasks. Animals were trained to perform an orientation match-to-sample task using either a visual or a tactile orientation sample. In a set of 89 neurons examined using both types of sample, 25% showed statistically significant effects of sample orientation regardless of whether the sample was visual or tactile. Most of these preferred the same sample orientation in both conditions. These results allow us to specify the nature of the information signaled by these neurons more precisely than has previously been possible.

For 193 units tested using one of the matching tasks, responses were also recorded while the animal performed a simple fixation task. In this task the animal was not required to attend to the visual stimuli that were presented. A few neurons that were responsive during the matching task were silent during fixation, but a comparable number was much more responsive during fixation. Across the whole population there was no systematic change in either responsivity or selectivity for orientation under the two conditions.

There are two subclasses of alpha cell in the mammalian retina, which are morphologically identical in plain view but have opposite responses to a luminance change: one is ON center and the other is OFF center. Recent studies have shown that the neural circuitries, which underlie light responses in such ON- and OFF-ganglion cell pairs, are not mirror symmetric with respect to the ON and OFF pathways (Pang et al., 2003; Zaghloul et al., 2003; Murphy & Rieke, 2006). This study examines alpha-cell homologues in the mouse retina and elucidates the synaptic mechanisms that generate their light responses. Morphological analysis of recorded cells revealed three subclasses that were essentially identical in plan view but had distinct vertical stratification levels. We refer to these cells as the sustained ON (ON-S), sustained OFF (OFF-S), and transient OFF (OFF-T) cells (Murphy & Rieke, 2006; Margolis & Detwiler, 2007). Both ON-S and OFF-S cells were largely driven through the ON pathway via changes in excitatory and inhibitory inputs, respectively. Light responses of OFF-T cells were driven by transient changes in excitatory and inhibitory inputs. Light responses of OFF-S cells were also measured in connexin 36 knockout mice in order to dissect glycinergic input arising from AII amacrine cells. At photopic/mesopic intensities, peak glycinergic input to OFF-S cells in the connexin 36 knockout mouse was reduced by ~85% compared to OFF-S cells in the wild-type retina. This is consistent with the idea that AII cells receive their input from ON-cone bipolar cells through gap junctions and in turn provide glycinergic inhibition to OFF-S cells.

Visual cortical areas are richly but selectively connected by “patchy” projections. We characterized these connections physiologically with cross-correlograms (CCHs), calculated for neuron pairs or small groups located one each in visual areas 17 and 18 of the cat. The CCHs were then compared to the visuotopic and orientation match of the neurons' receptive fields (RFs).

For both spontaneous and visually driven activity, most non-flat correlograms were centered; i.e. the most likely temporal relationship between spikes in the two areas is a synchronous one. Although spikes are most likely to occur simultaneously, area 17 spikes may occur before area 18 or vice versa, giving the cross-correlogram peak a finite width (temporal dispersion). Cross-correlograms fell into one of three groups according to their full-width at half peak height: 1–8 ms (modal width, 3 ms), 15–65 ms (modal width 30 ms), or 100–1000 ms (modal width 400 ms). These classificatory groups are nonoverlapping; the three types of coupling appeared singly and in combination.

Neurons whose receptive fields (RFs) are nonoverlapping or cross-oriented may yet be coupled, but the coupling is more likely to be the broadest type of coupling than the medium-dispersed type. The sharpest type of coupling is found exclusively between neurons with at least partially overlapping RFs and mostly between neurons whose stimulus orientation preferences matched to within 22.5 deg. The maximum spatial dispersion observed in the RFs of coupled neurons compares well with the maximum divergence seen anatomically in the A18/A17 projection system.

We suggest three different mechanisms to produce each of the three different degrees of observed spatial and temporal coherence. All mechanisms use common input of cortical origin. For medium and broad coupling, this common input arises from cell assemblies split between both sides of the 17/18 projection system, but acting synchronously. Such distributed common-input cell assemblies are a means of overcoming sparse connectivity and achieving synaptic transmission in the pyramidal network.

In in-vitro preparations of both macaque and human retina, intracellular injections of Neurobiotin and horseradish peroxidase were used to characterize the morphology, depth of stratification, and mosaic organization of a type of bistratified ganglion cell. This cell type, here called the small bistratified cell, has been shown to project to the parvocellular layers of the dorsal lateral geniculate nucleus (Rodieck, 1991) and is therefore likely to show color-opponent response properties.

In both human and macaque, the two dendritic tiers of the bistratified cell are narrowly stratified close to the inner and outer borders of the inner plexiform layer. The inner tier is larger in diameter and more densely branched than the outer tier and gives rise to distinct spine-like branchlets bearing large, often lobulated heads. By contrast the smaller, outer tier is sparsely branched and relatively spine-free.

In human retina, the small bistratified cells range in dendritic field diameter from ∼50 µm in central retina to ∼400 µm in the far periphery. The human small bistratified cells are about 20% larger in dendritic-field diameter than their counterparts in the macaque. However, when the difference in retinal magnification between human and macaque is taken into account, the small bistratified cells are similar in size in both species. In macaque, the small bistratified cell has a dendritic-field size that is ~10% larger than that of the magnocellular-projecting parasol ganglion cell. Human small bistratified ganglion cells tend to have smaller dendritic-field diameters than parasol cells. This is because parasol ganglion cells are larger in human than in macaque retina (Dacey & Petersen, 1992).

In macaque retina, intracellular injections of Neurobiotin revealed heterotypic tracer coupling to a distinct mosaic of amacrine cells and probable homotypic coupling to an array of neighboring ganglion cells around the perimeter of the injected cell's dendritic tree. The amacrine cell mosaic had a density of 1700 cells/mm2 in peripheral retina. Individual amacrines had small, densely branched and bistratified dendritic fields. From the homotypic coupling, it was possible to estimate for the small bistratified cell a coverage factor of ~1.8, and a density of ~1% of the total ganglion cells in central retina, increasing to ~6–10% in the retinal periphery.

The estimated density, dendritic-field size, and depth of stratification all suggest that the small bistratified ganglion cell type is the morphological counterpart of the common short-wavelength sensitive or ‘blue-ON’ physiological type.

We investigated the representation of color in cortical area V2 of macaque monkeys, and the association of color with other stimulus attributes. We measured the selectivity of individual V2 neurons for color, motion, and form. Most neurons in V2 were orientation selective, about half of them were selective for color, and a minority of cells (about 20%) were selective for size or direction. We correlated these physiological measurements with the anatomical location of the cells with respect to the cytochrome oxidase (CO) compartments of area V2. There was a tendency for color-selective cells to be found more frequently in the thin stripes, but color-selective cells also occurred frequently in thick stripes and inter-stripes. We found no difference in the degree of color selectivity between the different CO compartments. Furthermore, there was no negative correlation between color selectivity and selectivity for other stimulus attributes. We found many cells capable of encoding information along more than one stimulus dimension, regardless of their location with respect to the CO compartments. We suggest that area V2 plays an important role in integrating information about color, motion, and form. By this integration of stimulus attributes a cue-invariant representation of the visual world might be achieved.

We analyzed the relationship between eye movements and neuronal responses recorded from area MT in alert monkeys trained to maintain visual fixation during the presentation of moving patterns. The monkeys made small saccades which moved the eyes with velocities that spanned the sensitivity range of MT neurons. The saccades evoked changes in the neuronal response that depended upon (1) the level of stimulus-evoked activity amidst which the saccade occurred and (2) the direction of the saccade relative to the preferred direction of the neuron. Most notably, saccades were able to suppress stimulus-evoked activity when they caused retinal image flow that opposed the neuron's preference and were able to elicit a response or enhance weak activity when they caused flow in the neuron's preferred direction. On average, the disturbance lasted 40 ms beginning about 40 ms following saccade onset. Using these parameters, we simulated synthetic spike trains from an imaginary pair of similarly tuned neurons and determined that the interneuronal correlation due to saccades should be negligible at all but the lowest ongoing firing rates. This conclusion was supported from our data by the observation that response variance for single MT spike trains was not measurably reduced during periods of stable gaze compared to periods when eye movement exceeded a stability criterion (0.1 deg during 0.5 s). While the intrusions caused by saccades are too short-lived and infrequent to account for the variability of MT neuronal response (counter to the finding in V1 of Gur et al., 1997), the clear directional signal that they carry in area MT suggests that motion perception is not blocked during saccades by suppression at early stages in the visual pathway.

Both dopamine and melatonin are important for the regulation of retinal rhythmicity, and substantial evidence suggests that these two substances are mutually inhibitory factors that act as chemical analogs of day and night. A circadian oscillator in the mammalian retina regulates melatonin synthesis. Here we show a circadian rhythm of retinal dopamine content in the mouse retina, and examine the role of melatonin in its control. Using high-performance liquid chromatography (HPLC), we measured levels of dopamine and its two major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in retinas of C3H+/+ mice (which make melatonin) and C57BL/6J mice that are genetically incapable of melatonin synthesis. In a light/dark cycle both strains of mice exhibited daily rhythms of retinal dopamine, DOPAC, and HVA content. However, after 10 days in constant darkness (DD), a circadian rhythm in dopamine levels was present in C3H, but not in C57 mice. C57 mice given ten daily injections of melatonin in DD exhibited a robust circadian rhythm of retinal dopamine content whereas no such rhythm was present in saline-injected controls. Our results demonstrate that (1) a circadian clock generates rhythms of dopamine content in the C3H mouse retina, (2) mice lacking melatonin also lack circadian rhythms of dopamine content, and (3) dopamine rhythms can be generated in these mice by cyclic administration of exogenous melatonin. Our results also indicate that circadian rhythms of retinal dopamine depend upon the rhythmic presence of melatonin, but that cyclic light can drive dopamine rhythms in the absence of melatonin.

Age-related macular degeneration (AMD), affecting the retina, afflicts one out of ten people aged 80 years or older in the United States. AMD often results in vision loss to the central 15–20 deg of the visual field (i.e. central scotoma), and frequently afflicts both eyes. In most cases, when the central scotoma includes the fovea, patients will adopt an eccentric preferred retinal locus (PRL) for fixation. The onset of a central scotoma results in the absence of retinal inputs to corresponding regions of retinotopically mapped visual cortex. Animal studies have shown evidence for reorganization in adult mammals for such cortical areas following experimentally induced central scotomata. However, it is still unknown whether reorganization occurs in primary visual cortex (V1) of AMD patients. Nor is it known whether the adoption of a PRL corresponds to changes to the retinotopic mapping of V1. Two recent advances hold out the promise for addressing these issues and for contributing to the rehabilitation of AMD patients: improved methods for assessing visual function across the fields of AMD patients using the scanning laser ophthalmoscope, and the advent of brain-imaging methods for studying retinotopic mapping in humans. For the most part, specialists in these two areas come from different disciplines and communities, with few opportunities to interact. The purpose of this review is to summarize key findings on both the clinical and neuroscience issues related to questions about visual adaptation in AMD patients.