The compound lateral eye of the adult horseshoe crab, Limulus polyphemus, views the world with approximately 1000 ommatidia. Their optical properties and orientation determine the eye's resolution, field of view, and light collecting ability. Optic axes of adjacent ommatidia diverge from 1–15 deg with an average value of 5.5 deg yielding an average resolution of 0.1 cycles/deg. Resolution is not uniform across the eye: along horizontal planes, it is maximal in the anterior region of the eye (0.22 cycle/deg) and minimal in the posterior region (0.07 cycle/deg); along vertical planes, it is maximal near or just below the horizon (0.23 cycle/deg) and minimal above the horizon (0.04 cycle/deg). Together the ommatidia of one eye view approximately 60% of the hemispheric world on one side of the body. There is little binocular overlap (<1% of total field). Ommatidial facets of up to 320 μm in diameter (among the largest known in the animal kingdom) make the eye a superb light collector. Limulus are known to use vision to find mates both day and night. Apparently, the optics of the lateral eye sample a large enough part of the world with sufficient resolution and light-collecting ability for the animal to succeed at this essential task.

We have examined the integrity of the blood-brain barrier during optic nerve regeneration in the frog Liloria (Hyla) moorei using rhodamine B-labeled bovine serum albumin (RBA). A transient localized breakdown of the blood-brain barrier was observed between 1 and 5 weeks after extracranial optic nerve crush. The zone of breakdown progressed along the experimental optic nerve, ascended the opposite optic tract, and swept rostro-caudally across the tectum contralateral to the crushed nerve. By 7 weeks, the blood-brain barrier was once again intact along the length of the optic pathway. In a concurrent series of frogs, regenerating optic axons were visualized by anterograde transport of horseradish peroxidase (HRP). At each stage examined, the region reached by the front of regenerating axons corresponded to that in which the blood-brain barrier had been shown to break down.

In contrast to the results after nerve crush, the blood-brain barrier remained intact along the length of the optic pathway following optic nerve ligation to prevent regeneration. We conclude that the breakdown of the blood-brain barrier which occurs during optic nerve regeneration in the frog is triggered by the regenerating axons.

Recordings were made from single neurons in area 18 of anesthetized cats (N2O/O2 mixture supplemented by continuous intravenous infusion of barbiturate) in which one optic nerve had been pressure blocked to selectively block conduction in the largest (Y-type) fibers. Cortical neurons were stimulated visually via the normal eye or via the eye with the pressure-blocked optic nerve (“Y-blocked eye”). Several properties of the receptive fields such as their spatial organization (S or C cells), orientation tuning, and the presence and strength of end-zone inhibition appear to be unaffected by removal of the Y input. By contrast, the removal of the Y input resulted in a small but significant reduction in the size of the discharge field and in the direction-selectivity index. In three respects, peak response discharge rate, eye dominance, and velocity sensitivity, removal of the Y input had strong and highly significant effects. Thus, the mean peak discharge frequency of responses evoked by the stimulation of binocular neurons via the Y-blocked eye was significantly lower than that of responses evoked by the stimulation via the normal eye. Accordingly, the eye-dominance histogram was shifted markedly towards the normal eye (more so than in the homologous experiment conducted on area 17 — Burke et al., 1992). Finally, the mean preferred velocity of responses of cells activated via the normal eye was in the vicinity of 145 deg/s, whereas for cells activated via the Y-blocked eye the value was about 35 deg/s. Overall, the results of the present study imply that (1) apart from Y-type excitatory input there are significant excitatory non-Y-inputs to area 18; these inputs at least partially consist of indirect X-type input relayed via area 17; (2) in neurons of area 18 that receive both Y-type and non-Y-type excitatory inputs, the Y-type input has a major influence on strength of the response and velocity sensitivity and a lesser influence on the direction selectivity and size of the discharge fields; and (3) area 18 contains mechanisms determining such receptive-field properties as S- or C-type organization, orientation tuning, and direction selectivity which can be accessed either by the Y input or by non-Y input.

The effect of experimental strabismus on the development of vernier acuity and grating acuity was studied in Macaca nemestrina monkeys. Six monkeys were studied longitudinally beginning near 10 days after birth. Four of the six monkeys developed amblyopia. As is true for human strabismic amblyopes, the deficit in vernier acuity was larger than the deficit in grating acuity in the amblyopic monkeys. The developmental data reveal that this differential disruption of vernier acuity can be understood as a result of a slowed developmental process associated with amblyopia.

We found that a single intravitreal injection of 6-hydroxy dopamine (6-OHDA) is highly efficient in blocking the development of deprivation-induced myopia in young chickens. To investigate the effects of 6-OHDA on retinal function, we studied electroretinograms (ERGs) in chickens aged 15-25 days, 4 days subsequent to the injection. Both spectral sensitivity and oscillatory potentials were tested. In addition, a histological examination was performed of dopaminergic amacrine cells labeled by a monoclonal antibody against tyrosine hydroxylase. We found that, at doses of 6-OHDA sufficient to suppress deprivation myopia entirely, no effect could be detected on either the ERGs or on the density and appearance of dopaminergic amacrine cells. For higher doses, spectral sensitivity and the number of dopaminergic amacrine cells declined gradually. In contrast, as doses increased, oscillatory potentials 1 and 2 grew in amplitude only to decline at the highest doses. The results indicate that (1) development of deprivation myopia requires normal retinal function and that (2) slight changes in the gains of dopaminergic pathways are sufficient to block the development of deprivation myopia.

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.

Antibody labeling of the calcium-binding protein calbindin 28kD (CaBP) and gamma-aminobutyric acid (GABA) is altered by short-term monocular deprivation in the lateral geniculate nucleus and visual cortex of adult primates. It is not known whether these alterations occur in other subcortical visual structures. We therefore have examined antibody labeling to CaBP and GABA in the superior colliculus (SC) of visually deprived Rhesus monkeys. One group was monocularly enucleated as adults. The other monkeys experienced different types of monocular and binocular deprivation from birth, including occlusion of one eye, and/or surgically induced aphakia, optically corrected with extended-wear contact lenses, or an intraocular lens implant. Some of these monkeys also had one eye enucleated prior to perfusion.

In the SC of normal monkeys, CaBP-immunoreactive neurons formed three laminar tiers within SC, one within the zonal layer (ZL) and upper superficial gray layer (SGL), another bridging the optic and intermediate gray layers, and a third within the deep gray layer. CaBP neurons within the upper tier had small pyriform or stellate morphologies while those in the deeper tiers were slightly larger neurons, most with a stellate morphology. GABA-immunoreactive neurons were densely distributed within the SGL and more sparsely distributed within the deeper layers. These cells were mostly small neurons with horizontal, pyriform, or stellate morphologies.

Neither monocular enucleation nor occlusion nor aphakia combined with continuous occlusion of the fellow eye produced any visible reduction in antibody labeling in cells or neuropil within the SC. Full-field measures of labeling intensity (optical density) within the ZL and upper SGL revealed no consistent differences between the SC contralateral or ipsilateral to the affected eye in either CaBP- or GABA-labeled sections. Measures of the optical density, number, and size of labeled neurons also showed no consistent effects of enucleation and/or occlusion. We therefore conclude that the retino-geniculostriate and retino-collicular systems differ in their response to deprivation which is likely due to the significant overlap of retinal axons from the two eyes that occurs in the SC of the Rhesus monkey.

A circadian clock in the brain of the horseshoe crab, Limulus polyphemus, has an important role in the function of the peripheral visual system. At night, the clock transmits neural activity to the lateral, ventral, and median eyes via efferent optic nerve fibers. The activity occurs in synchronous bursts (maximum rate of 2 bursts/s) with individual efferent fibers contributing a single spike in each burst. The circadian efferent activity originates in the protocerebrum. Lateral connections synchronize the efferent activity recorded from the two halves of the protocerebrum, suggesting the existence of bilateral circadian oscillators. Circadian efferent activity survives excision of the brain and isolation of the protocerebrum. We conclude that circadian clock and its complex neural circuitry are fundamental components of the Limulus visual system.

We have investigated the effects of inactivation of localized sites in area 17 on the visual responses of cells in visuotopically corresponding regions of area 18. Experiments were performed on adult normal cats. The striate cortex was inactivated by the injection of nanoliters of lidocaine hydrochloride or of γ-aminobutyric acid (GABA) dissolved in a staining solution. Responses of the simple and complex cells of area 18 to optimally oriented light and dark bars moving in the two directions of motion were recorded before, during, and after the drug injection. Two main effects are described.

First, for a substantial number of cells, the drug injection provoked an overall reduction of the cell's visual responses. This nonspecific effect largely predominated in the complex cell family (76% of the units affected). This effect is consistent with the presence of long-range excitatory connections in the visual cortex.

Second, the inactivation of area 17 could affect specific receptive-field properties of cells in area 18. The main specific effect was a loss of direction selectivity of a number of cells in area 18, mainly in the simple family (more than 53% of the units affected). The change in direction selectivity comes either from a disinhibitory effect in the nonpreferred direction or from a reduction of response in the preferred direction. It is proposed that the disinhibitory effects were mediated by inhibitory interneurones within area 18. In a very few cases, the change of directional preference was associated with a modification of the cell's response profile.

These results showed that the signals from area 17 are necessary to drive a number of units in area 18, and that area 17 can contribute to, or at least modulate, the receptive-field properties of a large number of cells in the parastriate area.

A quantitative model is developed to predict the perceived direction of moving two-dimensional patterns. The model incorporates both a simple motion energy pathway and a “texture boundary motion” pathway that incorporates response squaring before the extraction of motion energy. These pathways correspond to Fourier and non-Fourier motion pathways and are hypothesized to reflect processing in the VI-MT and V1-V2-MT pathway, respectively. A cosine-weighted sum of these pathways followed by competitive feedback inhibition accurately predicts the perceived direction for patterns composed of two cosine gratings at different orientations (“plaids”). The model also predicts direction discrimination, differences between foveal and peripheral viewing, changes in perceived direction with exposure duration, motion masking, and motion transparency.

Disorder in the packing geometry of the human cone mosaic is believed to help alleviate spatial aliasing effects. To characterize cone packing geometry, we gathered positions of cone inner segments at seven locations along four primary and two oblique meridians in an adult human retina. We generated statistical descriptors based on the distribution of distances and angles to Voronoi neighbors. Parameters of a compressed-jittered model were fit to the actual mosaic. Local anisotropics were investigated using correlograms. We find that (1) median distance between Voronoi neighbors increases with eccentricity, but the minimum distance is constant (6–8 μm) across peripheral retina; (2) the cone mosaic is least compressed and jittered at the edge of the foveal rod-free zone; (3) disorder in the foveal center resembles that described by Pu m et al. (1990); (4) cone spacing is 10–15% less in one direction than in the orthogonal direction; and (5) cone spacing is greater in the radial direction (along meridians) than in the tangential direction (along lines of isoeccentricity). The nearly constant minimum distance implies that high spatial frequencies may be sampled even in peripheral retina. Local anisotropy of the cone mosaic is discussed in relation to the growth of the primate retina during development and to the orientation biases of retinal ganglion cells.

Deactivation of light-activated squid rhodopsin was studied in vitro using GTPγS binding by G-protein as a direct measure of rhodopsin activity. Deactivation was inhibited by dilution of the retinal suspension or by removal of soluble components. Deactivation could be restored by addition of soluble material to washed membranes. These results indicate that the deactivation is not due entirely to a conformational transition within rhodopsin itself, but depends on the interaction with other molecules. The possibility that phosphorylation is involved in the deactivation was studied. Deactivation occurred in the presence and absence of added ATP. Deactivation also occurred in the presence of kinase inhibitors and after addition of apyrase, which reduced residual ATP levels to below 1μM. These results indicate that light-induced phosphorylation is not required for deactivation of squid rhodopsin. In this regard deactivation of squid rhodopsin is different from that of vertebrate rhodopsin, which requires phosphorylation.

We have investigated the notion that directional responses of cells in the visual cortex depend on the type of stimulus used to drive the cell. Specifically, we have asked if sinusoidal gratings provide a different estimate of direction selectivity than bars that are brighter or darker than the background.

Using standard techniques, we recorded from 176 cells in the visual cortex of nine cats. For each cell, bright bars, dark bars, and sinusoidal gratings were presented in a randomly interleaved fashion. Complex cells exhibited around twice as many direction-selective as nondirection-selective responses. Estimates of direction selectivity were nearly identical for bright and dark bars and for gratings. For simple cells, a similar ratio of direction-selective to nondirection-selective responses was observed for gratings. However, a larger proportion of simple cells were classified as direction selective when bars were used for stimulation.

A simple cell that exhibited direction selectivity to a grating behaved in a similar manner when stimulated with bright or dark bars. However, in contrast to complex cells, some simple cells classed as directionally nonselective on the basis of their responses to gratings, displayed directionally selective behavior to bars. In addition, the preferred directions for dark and bright bars sometimes differed. These results demonstrate that the classification of a simple cell as directionally selective or nonselective can depend critically on the visual stimulus used.

The laminar and tangential organization of visual callosal projections of areas 17 and 18 were investigated in the adult ferret, using histochemical methods to visualize axonally transported horseradish peroxidase (HRP). Normal adult ferrets were given injections of HRP throughout one visual cortex or had gelfoam soaked in HRP applied to the transected corpus callosum. The ferret callosal cell distribution has a greater tangential extent in area 18 than in area 17. In addition, the radial organization of callosal cells in areas 17 and 18 differs: three times as many infragranular cells are present in area 18 than in area 17, although the number of supragranular cells is similar for both areas 17 and 18. Since the projections of alpha retinal ganglion cells are reported to be exclusively contralateral in the ferret (Vitek et al., 1985), callosal projections may make a major contribution to the binocularity of neurons in area 18.

Some neurochemical features of the neuronal circuitry regulating dopamine release were examined in the retina of the turtle, Pseudemys scripta elegans. Glutamate antagonists that block hyperpolarizing bipolar cells, such as 2,3 piperidine dicarboxylic acid (PDA), produced dose-dependent dopamine release. In contrast, the glutamate agonist 2-amino-4-phosphonobutyric acid (APB), which blocks depolarizing bipolar cell responses with high specificity, had no effect on the release of dopamine. The γ-aminobutyric acid (GABA) antagonist, bicuculline, also produced potent dose-dependent release of dopamine. The release of dopamine produced by PDA was blocked by exogenous GABA and muscimol, suggesting that the PDA-mediated release process was polysynaptic and involved a GABAergic synapse interposed between the bipolar and dopaminergic amacrine cells. The only other agents that produced dopamine release were chloride-free media and high extracellular K+; in particular, kainic acid and glutamate itself were ineffective. These results suggest that the primary neuronal chain mediating dopamine release in the turtle retina is: cone → hyperpolarizing bipolar cell → GABAergic amacrine cell → dopaminergic amacrine cell.

The response vs. contrast characteristics of different cell classes in the dorsal lateral geniculate nucleus (LGN) were compared. The luminance of a stationary flashing light spot was varied stepwise while the background luminance was constant. Lagged X cells had lower slope of the response vs. contrast curve (contrast gain), and they reached the midpoint of the response range over which the cells' response varied (dynamic response range) at higher contrasts than nonlagged X cells. These results indicated that nonlagged cells are well suited for detection of small contrasts, whereas lagged cells may discriminate between contrasts over a larger range. The contrast gain and the contrast corresponding to the midpoint of the dynamic response range were similar for X and Y cells. The latency to onset and to half-rise of the visual response decreased with increasing contrast, most pronounced for lagged cells. Even at the highest contrasts, the latency of lagged cells remained longer than for nonlagged cells. For many lagged cells, the latency to half-fall decreased with increasing contrast. It is shown that the differences in the response vs. contrast characteristics between lagged and nonlagged X cells in the cat are similar to the differences between the parvocellular and magnocellular neurones in the monkey.

Simple cells in the striate cortex have been depicted as half-wave-rectified linear operators. Complex cells have been depicted as energy mechanisms, constructed from the squared sum of the outputs of quadrature pairs of linear operators. However, the linear/energy model falls short of a complete explanation of striate cell responses. In this paper, a modified version of the linear/energy model is presented in which striate cells mutually inhibit one another, effectively normalizing their responses with respect to stimulus contrast. This paper reviews experimental measurements of striate cell responses, and shows that the new model explains a significantly larger body of physiological data.

Intracellular injections of Neurobiotin were used to determine whether the major ganglion cell classes of the macaque monkey retina, the magnocellular-projecting parasol, and the parvocellular-projecting midget cells showed evidence of cellular coupling similar to that recently described for cat retinal ganglion cells. Ganglion cells were labeled with the fluorescent dye acridine orange in an in vitro, isolated retina preparation and were selectively targeted for intracellular injection under direct microscopic control. The macaque midget cells, like the beta cells of the cat's retina, showed no evidence of tracer coupling when injected with Neurobiotin. By contrast, Neurobiotin-filled parasol cells, like cat alpha cells, showed a distinct pattern of tracer coupling to each other (homotypic coupling) and to amacrine cells (heterotypic coupling).

In instances of homotypic coupling, the injected parasol cell was surrounded by a regular array of 3–6 neighboring parasol cells. The somata and proximal dendrites of these tracer-coupled cells were lightly labeled and appeared to costratify with the injected cell. Analysis of the nearest-neighbor distances for the parasol cell clusters showed that dendritic-field overlap remained constant as dendritic-field size increased from 100–400 μm in diameter.

At least two amacrine cell types showed tracer coupling to parasol cells. One amacrine type had a small soma and thin, sparsely branching dendrites that extended for 1–2 mm in the inner plexiform layer. A second amacrine type had a relatively large soma, thick main dendrites, and distinct, axon-like processes that extended for at least 2–3 mm in the inner plexiform layer. The main dendrites of the large amacrine cells were closely apposed to the dendrites of parasol cells and may be the site of Neurobiotin transfer between the two cell types. We suggest that the tracer coupling between neighboring parasol cells takes place indirectly via the dendrites of the large amacrine cells and provides a mechanism, absent in midget cells, for increasing parasol cell receptive-field size and luminance contrast sensitivity.

The morphology of retinal ganglion cells within the central retina during formation of the fovea was examined in retinal explants with horseradish-peroxidase histochemistry. A foveal depression was first apparent in retinal wholemounts at embryonic day 112 (El 12; gestational term is approximately 165 days). At earlier fetal ages, the site of the future fovea was identified by several criteria that included peak density of ganglion cells, lack of blood vessels in the inner retinal layers, arcuate fiber bundles, and the absence of rod outer segments in the photoreceptor layer. Prior to E112, the terminal dendritic arbor of retinal ganglion cells within the central retina extended into the inner plexiform layer and were located directly beneath their somas of origin or at most were slightly displaced from it. For example, at E90 the mean horizontal displacement of the geometric center of the dendritic arbor from the somas of cells within 600 μm of the estimated center of the future fovea was 4.1 μm (S.D. 2.7, range 1.0-10.0, n = 97). Following formation of the foveal depression the dendritic arbors of cells were significantly displaced from their somas. For example, at E138 the mean displacement was 41.2 μm (S.D. 12.2, range 12.0-56.0, n = 97). The displacement of the dendritic arbor which occurred during this period was not accounted for by areal growth of the dendritic arbor, the somas, or the retina, but was produced by the lengthening of the primary dendritic trunk. Moreover, no significant displacement was observed within the remaining 1.5–6.5 mm of the central retina. These observations provide evidence supporting early speculations that the formation of the foveal pit occurs, in part, by the radial migration of ganglion cells from the center of the fovea during its formation. Our analyses suggest that this migration occurs by the lengthening of the primary dendrite presumably by the addition of membrane. This migration is in a direction opposite to the inward movement of photoreceptors that occurs during late fetal and early postnatal periods (Packer et al., 1990, Journal of Comparative Neurology 298, 472–493).