The dynamics of interactions between rod and L-cone driven signals were studied psychophysically in two deuteranopic observers. Flicker detection thresholds for different ratios of rod to L-cone modulation were measured at temporal frequencies between 1 and 15 Hz. A model, which assumes that rod and L-cone driven signals are vector added, can describe the threshold data adequately. We found that up to about 8–10 Hz temporal frequency, rod and L-cone signals interact additively, whereas at higher frequencies the interaction is subtractive. Rod and L-cone signal strengths depend similarly on temporal frequency and are maximal between 3 and 5 Hz. The phase difference between rod and L-cone signals increases linearly with temporal frequency, indicating that their responses have a delay difference of about 20 to 30 ms, consistent with involvement of the faster rod pathway. The data would suggest a nearly complete additivity of the rod and cone driven signals when using flashed stimuli. But, literature data showed only partial additivity of the two, suggesting that different postreceptoral mechanisms are involved in the two tasks.

Fish of the genus Anableps (Anablepidae, Cyprinodontiformes) have eyes that are adapted for simultaneous aerial and aquatic vision. In this study we investigate some of the corresponding retinal specializations of the adult Anableps anableps eye using retinal transverse sections and wholemounts. The linear dimensions of the retina were found to be asymmetric with a greater representation of the dorsal compared to the ventral visual field. The total number of neurons in the ganglion cell layer of the ventral hemiretina was on average 3.6 times greater than the values obtained in the dorsal hemiretina. Isodensity contour maps revealed a prominent horizontal visual streak in the ventral hemiretina with an average peak cell density of 18,286 cells/mm2. A second less-well-developed horizontal visual streak was also observed in the dorsal hemiretina. A sub-population of large cells with soma areas between 74 and 188 μm2 was identified and found to be distributed evenly across both hemiretinas. Together, these results show that the sampling gain of the ventral retina is significantly greater than the dorsal segment, that retinal specializations important for mediating acute vision are present in the parts of the visual field immediately above and below the surface of the water, and that visual functions related with the large ganglion cells require more even sampling across the visual field. The relevance of these retinal specializations to the feeding and other behavioral strategies adopted by Anableps is discussed.

The visual responsiveness and spatial tuning of frontal eye field (FEF) neurons were determined using a delayed memory saccade task. Neurons with visual responses were then tested for direction selectivity using moving random dot patterns centered in the visual receptive field. The preferred axis of motion showed a significant tendency to be aligned with the receptive-field location so as to favor motion toward or away from the center of gaze. Centrifugal (outward) motion was preferred over centripetal motion. Motion-sensitive neurons in FEF thus appear to have a direction bias at the population level. This bias may facilitate the detection or discrimination of expanding optic flow patterns. The direction bias is similar to that seen in visual area MT and in posterior parietal cortex, from which FEF receives afferent projections. The outward motion bias may explain asymmetries in saccades made to moving targets. A representation of optic flow in FEF might be useful for planning eye movements during navigation.

Neurons in the superficial layers of the midbrain superior colliculus (SC) exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the geniculocortical visual pathway, most respond best to visual stimuli that are smaller than the classical receptive field (RF). The mechanism underlying this size selectivity may depend on the number and pattern of feedforward retinal inputs and/or the balance between inhibition and excitation within the RF. We have previously shown that chronic blockade of NMDA receptors (NMDA-R), which increases the convergence of retinal afferents onto SC neurons, does not alter size selectivity in the SC. This suggests that the number of retinal inputs does not determine size selectivity. Here we show, using single unit extracellular recordings from the SC of normal hamsters, that size selectivity in neurons selective for small stimulus size is correlated with the strength of inhibition within the RF. We also show that dark rearing causes concomitant reductions in both inhibition and size selectivity. In addition, dark rearing increases the percentage of neurons non-selective for stimulus size. Finally, we show that chronic blockade of NMDA-R, a procedure that does not alter size tuning, also does not change the strength of inhibition within the RF. Taken together, these results argue that inhibition within the RF underlies selectivity for small stimulus size and that inhibition must be intact for size tuning to be preserved after developmental manipulations of activity. In addition, these results suggest that regulation of the balance between excitation and inhibition within the RF does not require NMDA-R activity but does depend on visual experience. These results suggest that developmental experience influences neural response properties through an alteration of inhibitory circuitry.

The role of chromatic information in 3-D shape perception is controversial. We resolve this controversy by showing that chromatic orientation flows are sufficient for accurate perception of 3-D shape. Chromatic flows required less cone contrast to convey shape than did achromatic flows, thus ruling out luminance artifacts as a problem. Luminance artifacts were also ruled out by a protanope's inability to see 3-D shape from chromatic flows. Since chromatic orientation flows can only be extracted from retinal images by neurons that are responsive to color modulations and selective for orientation, the psychophysical results also resolve the controversy over the existence of such neurons. In addition, we show that identification of 3-D shapes from chromatic flows can be masked by luminance modulations, indicating that it is subserved by orientation-tuned neurons sensitive to both chromatic and luminance modulations.

X-linked retinoschisis (XLRS) is a common form of inherited macular degeneration caused by mutations in the RS1 gene. Whereas the role of RS1 has been implicated in the synaptic structure as well as layer organization in the retina, the pathological effect of a defective RS1 gene on the synaptic interaction between photoreceptor cells and second-order neurons has not been thoroughly investigated. In this study, we perform a detailed characterization of the retinal synaptic phenotypes caused by a splice site mutation in the murine RS1 homolog (Rs1htmgc1). Electron microscopic analysis showed that presynaptic terminals of photoreceptor cells contain a lower areal density of synaptic vesicles in the Rs1htmgc1 retina. Examination of the synaptic interactions in the outer plexiform layer also revealed ectopic localization of photoreceptor cell presynaptic markers and elongation of neurites from postsynaptic neurons (bipolar and horizontal cells), which are observed in other mouse models with defective photoreceptor cell molecules. Consistent with these synaptic abnormalities, ERG analysis of young Rs1htmgc1 mice revealed attenuation of the b-wave with preservation of the a-wave. These results demonstrate that RS1H has functional significance in the morphology and function of the synapse between photoreceptors and second-order neurons. A developmental study from postnatal day (P) 15 through P19 showed that synaptic interactions form normally, and structural abnormalities occur after completion of synaptic formation suggesting that RS1H is important for the maintenance of this synaptic interaction. Thus, Rs1htmgc1 mice may serve as a new genetic model for human XLRS and other synaptic disorders.

We studied the temporal dynamics of shape representation in area V4 of the alert macaque monkey. Analyses were based on two large stimulus sets, one equivalent to the 2D shape stimuli used in a previous study of V2, and the other a set of stereoscopic 3D shape stimuli. As in V2, we found that information conveyed by individual V4 neurons about the stimuli tended to be maximal during the initial transient response and generally lower, albeit statistically significant, afterwards. The population response was substantially correlated from one stimulus to the next during the transients, and decorrelated as responses decayed. V4 responses showed significantly longer latencies than in V2, especially for the 3D stimulus set. Recordings from area V1 in a single animal revealed temporal dynamic patterns in response to the 2D shape stimuli that were largely similar to those in V2 and V4. Together with earlier results, these findings provide evidence for a distributed process of coarse-to-fine representation of shape stimuli in the visual cortex.

Psychophysical studies suggest that different colors have different perceptual status: red and blue for example are thought of as elementary sensations whereas yellowish green is not. The dominant account for such perceptual asymmetries attributes them to specificities of the neuronal representation of colors. Alternative accounts involve cultural or linguistic arguments. What these accounts have in common is the idea that there are no asymmetries in the physics of light and surfaces that could underlie the perceptual structure of colors, and this is why neuronal or cultural processes must be invoked as the essential underlying mechanisms that structure color perception. Here, we suggest a biological approach for surface reflection properties that takes into account only the information about light that is accessible to an organism given the photopigments it possesses, and we show that now asymmetries appear in the behavior of surfaces with respect to light. These asymmetries provide a classification of surface properties that turns out to be identical to the one observed in linguistic color categorization across numerous cultures, as pinned down by cross cultural studies. Further, we show that data from psychophysical studies about unique hues and hue cancellation are consistent with the viewpoint that stimuli reported by observers as special are those associated with this singularity-based categorization of surfaces under a standard illuminant. The approach predicts that unique blue and unique yellow should be aligned in chromatic space while unique red and unique green should not, a fact usually conjectured to result from nonlinearities in chromatic pathways.

Visually evoked extracellular neural activity was recorded from the nucleus isthmi (NI) of goldfish and bluegill sunfish. When moving anywhere within the right eye's visual field, three-dimensional checkered balls or patterns on a computer screen evoked bursts of spikes in the left NI. Object motion parallel to the longitudinal body axis gave responses that habituated markedly upon repetition, but movement into recently unstimulated regions of the visual field gave vigorous responses. Thus, while NI's response is not visuotopic, its habituation is. An object approaching the animal's body generated a rising spike density, whereas object recession generated only a transient burst. During the approach of a checkered stimulus ball, average NI spike density rose linearly as the ball-to-eye distance decreased and at a rate proportional to the ball's speed (2.5–30 cm/s). Increasing ball size (2.2–9.2 cm) did not affect the rate of activity rise at a given speed, but did increase overall activity levels. NI also responded reliably to expanding textures of fixed overall size. The results suggest that NI signals changes in motion of objects relative to the fish, and estimates the proximity of approaching objects.

The retinotopic organization of striate and several extrastriate areas of ferret cortex has been established. Here we describe the representation of the visual field on the Suprasylvian visual area (Ssy). This cortical region runs mediolaterally along the posterior bank of the suprasylvian sulcus, and is distinct from adjoining areas in anatomical architecture. The Ssy lies immediately rostral to visual area 21, medial to lateral temporal areas, and lateral to posterior parietal areas. In electrophysiological experiments we made extracellular recordings in adult ferrets. We find that single and multiunit receptive fields range in size from 2 deg × 4 deg to 21 deg × 52 deg. The total visual field representation in Ssy spans over 70 deg in azimuth in the contralateral hemifield (with a small incursion into the ipsilateral hemifield), and from +36 deg to −30 deg in elevation. There are often two representations of the horizontal meridian. Furthermore, the location of the transition from upper to lower fields varies among animals. General features of topography are confirmed in anatomical experiments in which we made tracer injections into different locations in Ssy, and determined the location of retrograde label in area 17. Both isoelevation and isoazimuth lines can span substantial rostrocaudal and mediolateral distances in cortex, sometimes forming closed contours. This topography results in cortical magnifications averaging 0.07 mm/deg in elevation and 0.06 mm/deg in azimuth; however, some contours can run in such a way that it is possible to move a large distance on cortex without moving in the visual field. Because of these irregularities, Ssy contains a coarse representation of the contralateral visual field.

To what extent do observers' judgments of surface color with natural scenes depend on global image statistics? To address this question, a psychophysical experiment was performed in which images of natural scenes under two successive daylights were presented on a computer-controlled high-resolution color monitor. Observers reported whether there was a change in reflectance of a test surface in the scene. The scenes were obtained with a hyperspectral imaging system and included variously trees, shrubs, grasses, ferns, flowers, rocks, and buildings. Discrimination performance, quantified on a scale of 0 to 1 with a color-constancy index, varied from 0.69 to 0.97 over 21 scenes and two illuminant changes, from a correlated color temperature of 25,000 K to 6700 K and from 4000 K to 6700 K. The best account of these effects was provided by receptor-based rather than colorimetric properties of the images. Thus, in a linear regression, 43% of the variance in constancy index was explained by the log of the mean relative deviation in spatial cone-excitation ratios evaluated globally across the two images of a scene. A further 20% was explained by including the mean chroma of the first image and its difference from that of the second image and a further 7% by the mean difference in hue. Together, all four global color properties accounted for 70% of the variance and provided a good fit to the effects of scene and of illuminant change on color constancy, and, additionally, of changing test-surface position. By contrast, a spatial-frequency analysis of the images showed that the gradient of the luminance amplitude spectrum accounted for only 5% of the variance.

Opsins, like many other G-protein-coupled receptors, sustain constitutive activity in the absence of ligand. In partially bleached rods and cones, opsin's activity closes cGMP-gated channels and produces a state of “pigment adaptation” with reduced sensitivity to light and accelerated flash response kinetics. The truncated retinal analogue, β-ionone, further desensitizes partially bleached green-sensitive salamander rods, but enables partially bleached red-sensitive cones to recover dark-adapted physiology. Structural differences between rod and cone opsins were proposed to explain the effect. Rods and cones, however, also contain different transducins, raising the possibility that G-protein type determines the photoreceptor-specific effects of β-ionone. To test the two hypotheses, we applied β-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively. Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. β-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones. Furthermore, all recombinant salamander rod and cone opsins, with the exception of the red-sensitive cone opsin, activated rod transducin upon the addition of β-ionone. Thus opsin structure determines the identity of β-ionone as an agonist or an inverse agonist and in that respect distinguishes the red-sensitive cone opsin from all others.

We have examined the distribution of metabotropic glutamate receptors (mGluRs) 1 and 5 in the adult chicken retina using preembedding immuno-electronmicroscopy. Immunoreactivity for mGluRs 1 and 5 was found in both the outer plexiform layer (OPL) and the inner plexiform layer (IPL). For mGluR1, OPL labeling was observed at cone pedicles and horizontal and bipolar cell processes. In the IPL, mGluR1 labeling could be found on bipolar cell terminals, as well as postsynaptic processes, including amacrine cell processes. Neither presynaptic nor postsynaptic elements were labeled at rod synapses. For mGluR5, OPL labeling was associated with cone pedicles as well as bipolar and horizontal cell processes. As for mGluR1, rod synapses were unlabeled. In the IPL, labeling for mGluR5 was found on bipolar cell terminals and amacrine cell processes. The presynaptic expression of these receptors in the OPL was confirmed at the light level by double-labeling experiments with SV2. The distributions of mGluRs 1 and 5 indicate that they have the potential to regulate function in both synaptic layers. Furthermore, the similar expression patterns for these two receptors indicate that they might be co-expressed and thus have the potential to interact functionally.

The mammalian retina contains approximately 30 different morphological types of amacrine cells, receiving glutamatergic input from bipolar cells. In this study, we combined electrophysiological and pharmacological techniques in order to study the glutamate receptors expressed by different types of amacrine cells. Whole-cell currents were recorded from amacrine cells in vertical slices of the mouse retina. During the recordings the cells were filled with Lucifer Yellow/Neurobiotin allowing classification as wide-field or narrow-field amacrine cells. Amacrine cell recordings were also carried out in a transgenic mouse line whose glycinergic amacrine cells express enhanced green fluorescent protein (EGFP). Agonist-induced currents were elicited by exogenous application of NMDA, AMPA, and kainate (KA) while holding cells at −75 mV. Using a variety of specific agonists and antagonists (NBQX, AP5, cyclothiazide, GYKI 52466, GYKI 53655, SYM 2081) responses mediated by AMPA, KA, and NMDA receptors could be dissected. All cells (n = 300) showed prominent responses to non-NMDA agonists. Some cells expressed AMPA receptors exclusively and some cells expressed KA receptors exclusively. In the majority of cells both receptor types could be identified. NMDA receptors were observed in about 75% of the wide-field amacrine cells and in less than half of the narrow-field amacrine cells. Our results confirm that different amacrine cell types express distinct sets of ionotropic glutamate receptors, which may be critical in conferring their unique temporal responses to this diverse neuronal class.

Over the last 50 years, studies of receptive fields in the early mammalian visual system have identified many classes of response properties in brain areas such as retina, lateral geniculate nucleus (LGN), and primary visual cortex (V1). Recently, there has been significant interest in understanding the cellular and network mechanisms that underlie these visual responses and their functional architecture. Small mammals like rodents offer many advantages for such studies, because they are appropriate for a wide variety of experimental techniques. However, the traditional rodent models, mice and rats, do not rely heavily on vision and have small visual brain areas. Squirrels are highly visual rodents that may be excellent model preparations for understanding mechanisms of function and disease in the human visual system. They use vision for navigating in their environment, predator avoidance, and foraging for food. Visual brain areas such as LGN, V1, superior colliculus, and pulvinar are particularly large and well elaborated in the squirrel, and the squirrel has several extrastriate cortical areas lateral to V1. Unlike many mammals, most squirrel species are diurnal with cone-dominated retinas, similar to the primate fovea, and have excellent dichromatic color vision that is mediated by green and blue cones. Owing to their larger size, squirrels are physiologically more robust than mice and rats under anesthesia, and some hibernating species are particularly tolerant of hypoxia that occurs during procedures such as brain slicing. Finally, many basic anatomical and physiological properties in the early visual system of squirrel have now been described, permitting investigations of cellular mechanisms. In this article, we review four decades of anatomical, behavioral, and physiological studies in squirrel and make comparisons with other species.

Most of the blinding retinopathies are due to progressive photoreceptor degeneration. Treatment paradigms that are currently being investigated include strategies to either halt or slow down photoreceptor cell loss, or to replace useful vision with retinal prosthesis. However, more information is required on the pathophysiological changes of the diseased retina, in particular the inner retina, that occur as a consequence of photoreceptor cell loss. Here we wished to use light damage as a stoppable insult to determine the structural and functional consequences on inner and outer retina, with the overall goal of determining whether survival of a functional inner retina is possible even if the outer retina is damaged. Mice were exposed to a 20-day light-damage period. Electroretinograms (ERG) and morphology were used to assess subsequent recovery. Outer retina was monitored analyzing a-waves, which represent photoreceptor cell responses, and histology. Integrity of the inner retina was monitored, analyzing b-waves and oscillatory potentials (OP1–OP4) and immunohistochemical markers for known proteins of the inner retina. All six ERG components were significantly suppressed with respect to amplitudes and kinetics, but stabilized in a wave-dependent manner within 40–70 days after the end of light exposure. As expected, damage of the outer retina was permanent. However, function of the inner retina was found to recover significantly. While b-wave amplitudes remained suppressed to 60% of their baseline values, OP amplitudes recovered completely, and implicit times of all components of the inner retina (b-wave and OP1–OP4) recovered to a level close to baseline values. Histological analyses confirmed the lack of permanent damage to the inner retina. In summary, these data suggests that the inner retina has the potential for significant recovery as well as plasticity if treatment is available to stop the deterioration of the outer retina.

Temporal interactions in direction-sensitive complex cells in area 18 and the posteromedial lateral suprasylvian cortex (PMLS) were studied using a reverse correlation method. Reverse correlograms to combinations of two temporally separated motion directions were examined and compared in the two areas. A comparison to the first-order reverse correlograms allowed us to identify nonlinear suppression or facilitation due to pairwise combinations of motion directions. Results for area 18 and PMLS were very different. Area 18 showed a single type of nonlinear behavior: similar directions facilitated and opposite directions suppressed spike probability. This effect was most pronounced for motion steps that followed each other immediately and decreased with increasing delay between steps. In PMLS, the picture was much more diverse. Some cells exhibited nonlinear interactions, that were opposite to those in area 18 (facilitation for opposite directions and suppression for similar ones), while the majority did not show a systematic interaction profile. We conclude that nonlinear second-order reverse correlation characteristics reveal different functional properties, despite similarities in the first-order reverse correlation profiles. Directional interactions in time revealed optimal integration of similar directions in area 18, but motion opponency—at least in some cells—in PMLS.

Metabotropic glutamate receptor 6 (mGluR6) is a group III, pertussis toxin (PTX)-sensitive G protein coupled mGluR that plays a specialized role in the retina. Retinal ON bipolar cells, which receive direct glutamatergic input from photoreceptor cells, express mGluR6 as their primary postsynaptic glutamate receptor. Activation of mGluR6 in these cells initiates an intracellular signaling cascade ultimately leading to inhibition of a cation channel and cell hyperpolarization. The primary mediator of this pathway in vivo is Gαo, but the potential roles of other G proteins from the Gαi/o family in the regulation of this or other signaling pathways in ON bipolar cells are unclear. To determine which specific G proteins from the Gαi/o family are able to couple to mGluR6, a Gα reconstitution system was employed using PTX-insensitive Gα mutants expressed with mGluR6 in PTX-treated sympathetic neurons from the rat superior cervical ganglion (SCG). The efficiency of coupling to mGluR6 was Goa > Gob, Gi1 > Gi2, Gi3, whereas no coupling was observed with Gαz, nor with the retinal Gα proteins, rod (GNAT2) or cone (GNAT1) transducin (GαTr-R, GαTr-C). Finally, the expression of Gα proteins determined to couple with mGluR6 was examined in rat ON bipolar cells using single cell RT-PCR. Co-expression of mGluR6 message was used to distinguish ON from OFF bipolar cells. Expression of Gαo was detected in every ON bipolar cell examined. Message for Gαi1, which coupled moderately to mGluR6, was not detected in ON bipolar cells, nor was Gαi3, which coupled to mGluR6 in only a few cells but on average did not exhibit statistically significant coupling. Finally, though Gαi2 was detectable in ON bipolar cells, its coupling to mGluR6 in the SCG system was not significant. Together, these data indicate that signaling through mGluR6 in mammalian ON bipolar cells is highly focused, apparently acting through a single Gα protein subtype.

Observers can generally make reliable judgments of surface color in natural scenes despite changes in an illuminant that is out of view. This ability has sometimes been attributed to observers' estimating the spectral properties of the illuminant in order to compensate for its effects. To test this hypothesis, two surface-color-matching experiments were performed with images of natural scenes obtained from high-resolution hyperspectral images. In the first experiment, the sky illuminating the scene was directly visible to the observer, and its color was manipulated. In the second experiment, a large gray sphere was introduced into the scene so that its illumination by the sun and sky was also directly visible to the observer, and the color of that illumination was manipulated. Although the degree of color constancy varied across this and other variations of the images, there was no reliable effect of illuminant color. Even when the sky was eliminated from view, color constancy did not worsen. Judging surface color in natural scenes seems to be independent of an explicit illuminant cue.

Brisk Y-type ganglion cells in the cat retina exhibit a high frequency resonance (HFR) in their responses to large, rapidly modulated stimuli. We used a computer model to test whether negative feedback mediated by axon-bearing amacrine cells onto ganglion cells could account for the experimentally observed properties of HFRs. Temporal modulation transfer functions (tMTFs) recorded from model ganglion cells exhibited HFR peaks whose amplitude, width, and locations were qualitatively consistent with experimental data. Moreover, the wide spatial distribution of axon-mediated feedback accounted for the observed increase in HFR amplitude with stimulus size. Model phase plots were qualitatively similar to those recorded from Y ganglion cells, including an anomalous phase advance that in our model coincided with the amplification of low-order harmonics that overlapped the HFR peak. When axon-mediated feedback in the model was directed primarily to bipolar cells, whose synaptic output was graded, or else when the model was replaced with a simple cascade of linear filters, it was possible to produce large HFR peaks but the region of anomalous phase advance was always eliminated, suggesting the critical involvement of strongly non-linear feedback loops. To investigate whether HFRs might contribute to visual processing, we simulated high frequency ocular tremor by rapidly modulating a naturalistic image. Visual signals riding on top of the imposed jitter conveyed an enhanced representation of large objects. We conclude that by amplifying responses to ocular tremor, HFRs may selectively enhance the processing of large image features.