The goal of this study was an administration of the navigation task in a three-dimensional virtual environment to localize the electroencephalogram (EEG) features responsible for egocentric and allocentric reference frame processing in a horizontal and also in a vertical plane. We recorded the EEG signal of a traverse through a virtual tunnel to search for the best signal features that discriminate between specific strategies in particular plane. We identified intrahemispheric coherences in occipital–parietal and temporal–parietal areas as the most discriminative features. They have 10% lower error rate compared to single electrode features adopted in previous studies. The behavioral analysis revealed that 11% of participants switched from egocentric to allocentric strategy in a vertical plane, while 24% of participants consistently adopted egocentric strategy in both planes.

Comparisons of S- or prepotential activity, thought to derive from a retinal ganglion cell afferent, with the activity of relay cells of the lateral geniculate nucleus (LGN) have sometimes implied a loss, or leak, of visual information. The idea of the “leaky” relay cell is reconsidered in the present analysis of prepotential firing and LGN responses of color-opponent cells of the macaque LGN to stimuli varying in size, relative luminance, and spectral distribution. Above a threshold prepotential spike frequency, called the signal transfer threshold (STT), there is a range of more than 2 log units of test field luminance that has a 1:1 relationship between prepotential- and LGN-cell firing rates. Consequently, above this threshold, the LGN cell response can be viewed as an extension of prepotential firing (a “nonleaky relay cell”). The STT level decreased when the size of the stimulus increased beyond the classical receptive field center, indicating that the LGN cell is influenced by factors other than the prepotential input. For opponent ON cells, both the excitatory and the inhibitory response decreased similarly when the test field size increased beyond the center of the receptive field. These findings have consequences for the modeling of LGN cell responses and transmission of visual information, particularly for small fields. For instance, for LGN ON cells, information in the prepotential intensity–response curve for firing rates below the STT is left to be discriminated by OFF cells. Consequently, for a given light adaptation, the STT improves the separation of the response range of retinal ganglion cells into “complementary” ON and OFF pathways.

We describe the temporal pattern of mRNA expression of some of the molecular components of the NO/cGMP second messenger system in the developing rat visual cortex and the effect of dark rearing on their expression levels using semiquantitative RT-PCR. mRNA expression for these molecules was altered by dark rearing in one of three ways: (1) no change—rod, olfactory, and cone/testis CNG channels, nonselective cation channels gated by cyclic nucleotides and highly permeable to Ca2+; (2) decrease—cyclic nucleotide phosphodiesterases which regulate cyclic nucleotide levels, and soluble guanylyl cyclase, the key synthetic enzyme producing cGMP and potently activated by nitric oxide; and (3) increase—cGMP kinase I, a key enzyme activated by cGMP to phosphorylate a variety of intracellular proteins including cytoskeletal elements. These data suggest important and distinct roles for the cGMP system in both early and late developmental events in the rat visual cortex.

A moving stimulus paradigm was designed to investigate color contrast encoding in the retina. Recently, this paradigm yielded suggestive evidence for color contrast encoding in zebrafish but the significance and generality remain uncertain since the properties of color coding in the zebrafish inner retina are largely unknown. Here, the question of color contrast is pursued in the goldfish retina where there is much accumulated evidence for retinal mechanisms of color vision and opponent color-coding, in particular. Recordings of a sensitive local field potential of the inner retina, the proximal negative response, were made in the intact, superfused retina in the light-adapted state. Responses to color contrast and achromatic contrast were analyzed by comparing responses to a green moving bar on green versus red backgrounds. The quantitative form of the irradiance/response curves was distinctly different under a range of conditions in 32 retinas, thereby providing robust evidence for red–green color contrast. The color contrast is based on successive contrast, occurs in the absence of overt color opponency, and clearly differs from previous findings in the goldfish retina for simultaneous color contrast mediated by color-opponent neurons. The form of the irradiance/response curves suggests that successive color contrast is particularly important when achromatic contrast is low, as often occurs in natural environments. The present results provide a parallel with the well-known principle of human color vision, first proposed by Kirschmann as the third law of color contrast, and may also have implications for the evolution of vertebrate color vision.

The antibody H386F revealed microglia in the retinae of several species: owl monkey, slow loris, galago, ferret, raccoon, and tree shrew. The shape, size, and density of labeled microglia were identical to those labeled by OX-42 and OX-41, two antibodies specific for microglia, in both galago and owl monkey. The labeled microglia varied little in retinal location. There was remarkably little variability in density, shape, number, and size of the abeled microglia between species. All labeled microglia were evenly distributed across, but restricted to, the nerve liber layer. Possible reasons for this restriction in location are discussed.

Normal photoreceptor cells on the ventral nerve of Limulus respond to a moderately intense flash with a large receptor potential or current. Occasionally, cells are found in which the same flash evokes only a small receptor potential or current. Our investigations reveal physiological reasons for the poor light sensitivity in these “unusual cells.” In unusual cells prolonged illumination with intense light evokes a step-like inward current with an amplitude of some nanoamperes, but without a large transient peak. The current appears to be summed up of single photon responses with amplitudes smaller than about 50 pA. Their time course is similar to that of small single photon responses forming the so-called macroscopic C1 component in normal cells. The macroscopic current evoked by an intense flash has slow activation and deactivation kinetics and reaches a saturated amplitude of about 4–5 nanoamperes. The light-intensity dependence of the current evoked by flashes or by prolonged illumination has a slope of about 1 in log–log plots. The decay kinetics of the current is similar to that of the C1 component measured in normal cells after the block of the C2 component. Occasionally, the step-like current is superposed by large standard bumps. These bumps are blocked by the Ca2+-ATPase inhibitor cyclopiazonic acid, while the sustained inward current persists. We conclude that in unusual cells the light-activated current is identical to the C1 component of normal cells. The phospholipase C pathway that in normal cells presumably gives rise to the C2 component functions only with a low efficiency in unusual cells.

The nucleus glomerulosus (NG) in paracanthopterygian and acanthopterygian teleost fishes receives afferents from neurons of the nucleus corticalis (NC), whose dendrites extend to the layers, stratum fibrosum et griseum superficiale (SFGS) and stratum griseum centrale (SGC), of the tectum opticum. A re-examination in this study revealed, by means of tracer experiments using biotinylated dextran amine, a separation among both tectal layers, portions of the NC, and target areas in a laminated type of the NG in the South American pufferfish, Colomesus asellus. Neurons of the lateral part of the NC send their dendrites to the SFGS and project to an area located dorsolaterally and centrally in the NG. In contrast, dendrites from neurons of the medial part of the NC run to the SGC, and projections from these neurons terminate in the NG in an area extending from dorsomedial to ventrolateral in the outer portion. Therefore, these two areas in the NG receive input from different sources. The NG in the visual system of tetraodontids may be involved in higher cognitive functions requiring much energy, becoming apparent by its very high level of cytochrome c oxidase activity.

Detection of illusory contours (ICs) such as Kanizsa figures is known to depend primarily upon the lateral occipital complex. Yet there is no universal agreement on the role of the primary visual cortex in this process; some existing evidence hints that an early stage of the visual response in V1 may involve relative suppression to Kanizsa figures compared with controls. Iso-oriented luminance borders, which are responsible for Kanizsa illusion, may evoke surround suppression in V1 and adjacent areas leading to the reduction in the initial response to Kanizsa figures. We attempted to test the existence, as well as to find localization and timing of the early suppression effect produced by Kanizsa figures in adult nonclinical human participants. We used two sizes of visual stimuli (4.5 and 9.0°) in order to probe the effect at two different levels of eccentricity; the stimuli were presented centrally in passive viewing conditions. We recorded magnetoencephalogram, which is more sensitive than electroencephalogram to activity originating from V1 and V2 areas. We restricted our analysis to the medial occipital area and the occipital pole, and to a 40–120 ms time window after the stimulus onset. By applying threshold-free cluster enhancement technique in combination with permutation statistics, we were able to detect the inverted IC effect—a relative suppression of the response to the Kanizsa figures compared with the control stimuli. The current finding is highly compatible with the explanation involving surround suppression evoked by iso-oriented collinear borders. The effect may be related to the principle of sparse coding, according to which V1 suppresses representations of inner parts of collinear assemblies as being informationally redundant. Such a mechanism is likely to be an important preliminary step preceding object contour detection.

Several lines of evidence suggest that, as concentrations of two agonists of group III metabotropic glutamate receptors are increased, cone contributions to the b-wave are blocked before rod contributions. Application of L-AP5 (L-2-amino-5-phosphonobutyric acid) at concentrations of 50 μM and D,L-AP4 (D,L-2-amino-4-phosphonobutyric acid) at concentrations 2 μM had a greater effect in reducing the amplitude of the rat ERG b-wave at high light intensities than at low light intensities. The amplitude reduction occurs at flash intensities that saturate rod photoreceptor responses. When steady backgrounds are used to saturate rod photoreceptors, the b-wave responses show increased long-wavelength sensitivity. Responses on a rod saturating background are blocked by adding L-AP5 or AP4 at the above concentrations to the perfusate. Further evidence for metabotrophic receptors being involved comes from the observation that even when ionotropic glutamate receptors are pharmacologically blocked with MK801 and DNQX, AP4 selectively blocks cone contributions to the b-wave. Thus we suggest that the type III metabotrophic receptors on depolarizing cone bipolar cells or cone synaptic terminals are affected by concentrations of L-AP5 and D,L-AP4 that have minimal effects on rod bipolar cells or rod synaptic terminals.

Limulus photoreceptors utilize the phosphoinositide pathway to generate light-induced single photon events (quantum bumps) that sum to form the depolarizing receptor potential. The protein kinase C (PKC) activator, (−)-indolactam V (ILV) rapidly desensitizes the light response in Limulus ventral nerve photoreceptors. Within 10 min of extracellular application, 100 nM (−)-ILV caused a decrease in the mean amplitude of quantum bumps to 38% of control values. PKC activation by (−)-ILV also causes photosensitive membrane disorganization and endocytosis. To investigate whether this precedes desensitization of the electrical response, we fixed cells after 10-min incubation with 25 μM (−)-ILV, a concentration sufficient to cause a 1000-fold desensitization of the receptor potential. The photosensitive microvilli of these photoreceptors remained narrow, densely packed, and well organized. Increasing the incubation time to 60 min did, however, induce disorganization and swelling of the microvilli and endocytosis of the photosensitive membrane, as previously reported. Measurement of membrane capacitance did not indicate a significant reduction in membrane area accompanying desensitization by (−)-ILV. PKC-induced reduction in light sensitivity therefore precedes the detection of ultrastructural changes in the rhabdomeral membrane and is not due to a net loss of membrane.

Following up on a prior study of contour and brightness processing in visual masking (Breitmeyer et al., 2006), we investigated the effects of a binocular and dichoptic para-contrast masking on the visibility of the contour and brightness of a target presented to the other eye. Combined, the results support the contributions of several cortical processes to para-contrast: (1) two central sources of inhibition, one long-latency and prolonged and the other short-latency and brief; (2) binocular rivalry suppression; and (3) a facilitatory effect peaking at different SOAs for the contour and the brightness tasks, reflecting; (4) known properties of two separate cortical systems, one a fast contour-processing pathway and the other a slower brightness-processing pathway.

Unlike simple cells, complex cells of area 18 give a directionally selective response to motion of random textures, indicating that they may play a special role in motion detection. We therefore investigated how texture motion, and especially its velocity, is represented by area 18 complex cells. Do these cells have separable spatial and temporal tunings or are these nonseparable? To answer this question, we measured responses to moving random pixel arrays as a function of both pixel size and velocity, for a set of 63 directionally selective complex cells. Complex cells generally responded to a fairly wide range of pixel sizes and velocities. Variations in pixel size of the random pixel array only caused minor changes in the cells' preferred velocity. For nearly all cells the data much better fitted a model in which pixel size and velocity act separately, than a model in which pixel size and velocity interact so as to keep temporal-frequency sensitivity constant. Our conclusion is that the studied population of special complex cells in area 18 are true motion detectors, rather than temporal-frequency tuned neurons.

The horizontal cells are known to form a mono-layered mosaic in the adult retina, but are scattered at different retinal depths in early development. To help clarifying when and which spatial constraints appear in the relative positioning of these cells, we have performed a quantitative analysis of the three-dimensional (3D) organization of the horizontal cell mosaic at different developmental stages in the postnatal rat retina. We first analyzed the two-dimensional (2D) distribution of the horizontal cell projections onto a plane parallel to the upper retinal surface in retinal flat-mounts, and thus to the future mature horizontal cell mosaic. We found that this 2D distribution was non random since postnatal day 1 (P1), and had a subsequent stepwise improvement in regularity. This preceded the alignment of cells in a single monolayer, which was observed on P6. We then computed true horizontal cell spacing in 3D, finding non-random 3D positioning already on P1. Simulation studies showed that this order might simply derive from the 2D order observed in the projections of the cells in flat-mount, combined with their limited spread in retinal depth. Throughout the period analyzed, the relative positions of horizontal cells are in good agreement with a minimal spacing rule in which the exclusion zone corresponds to the average size of the inner core of the cell dendritic tree estimated from P1 samples. These data indicate the existence of different phases in the process of horizontal cell 3D spatial ordering, supporting the view that multiple mechanisms are involved in the development of the horizontal cell mosaic.

Previously, we reported the myelin regulatory factor (MYRF) as a candidate gene for nanophthalmos. We have also produced Myrf knockdown (Myrf+/−) mouse strain to investigate the cellular and molecular phenotypes of reduced MYRF expression in the retina. Myrf+/− mouse strain was generated using the CRISPR/Cas9 system. Optomotor response system, electroretinogram (ERG), spectral-domain optical coherence tomography (SD-OCT), histology, and immunohistochemistry were performed to evaluate retinal spatial vision, electrophysiological function, retinal thickness, and pathological changes in cone or rod photoreceptors, respectively. RNA sequencing (RNA-seq) was performed to investigate the underlying molecular mechanism linking Myrf deficiency with photoreceptor defects. The genotype and phenotype of CRISPR/Cas9-induced Myrf+/− mice and their offspring were comprehensively investigated. Photoreceptor defects were detected in the retinas of Myrf+/− mice. Visual acuity and ERG responses were decreased in Myrf+/− mice compared with the control mice (Myrf+/+). The loss of cone and rod neurons was proportional to the decreased outer nuclear layer (ONL) thickness. Moreover, RNA-seq revealed that phototransduction and estrogen signaling pathways played important roles in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Myrf+/− mouse strain provides a good model to investigate the function of the MYRF gene. Photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology indicate an important role played by MYRF in retinal development. Alterations in phototransduction and estrogen signaling pathways play important roles in linking Myrf deficiency with retinal photoreceptor defects.

The medial part of the nucleus of Edinger–Westphal (EWM) in birds mediates light-regulated adaptive increases in choroidal blood flow (ChBF). We sought to characterize the effect of loss of EWM-mediated ChBF regulation on photoreceptor health in pigeons housed in either moderate intensity diurnal or constant light (CL). Photoreceptor abundance following complete EWM destruction was compared to that following a lesion in the pupil control circuit (as a control for spread of EWM lesions to the nearby pupil-controlling lateral EW) or following no EW damage. Birds were housed post-lesion in a 12 h 400 lux light/12 h dark light cycle for up to 16.5 months, or in constant 400 lux light for up to 3 weeks. Paraformaldehyde–glutaraldehyde fixed eyes were embedded in plastic, sectioned, slide-mounted, and stained with toluidine blue/azure II. Blinded analysis of photoreceptor outer segment abundance was performed, with outer segment types distinguished by oil droplet tint and laminar position. Brains were examined histologically to assess lesion accuracy. Disruption of pupil control had no adverse effect on photoreceptor outer segment abundance in either diurnal light or CL, but EWM destruction led to 50–60% loss of blue/violet cone outer segments in both light conditions, and a 42% loss of principal cone outer segments in CL. The findings indicate that adaptive regulation of ChBF by the EWM circuit plays a role in maintaining photoreceptor health and mitigates the harmful effect of light on photoreceptors, especially short wavelength-sensitive cone photoreceptors.

This study presents a morphological and quantitative analysis of displaced ganglion cells performed in the chick retina at different stages of development (E11, E17, & P2). The lipophilic dye DiI inserted into the optic nerve provided a complete staining of displaced ganglion cell population and of their dendritic trees. From 11 days of incubation (E11) all neurons present a uniform morphology and are unmistakably recognizable by the dimensions of their cell body and by the presence of the axon. Their dendritic arborizations shape a complex network through the retina. Cell bodies are randomly distributed but dendritic trees of neighboring cells constantly present two levels of dendritic overlap: about 50% of the cells present a high degree of overlap, more than the 30% up to 95% of their total area, while the other half overlaps less than 20%. The high degree of overlap identifies a cluster, which is regularly formed by three and more rarely by four neurons starting from 17 days of incubation (E17) onward and after birth. From E17 onward, 94% of clusters is constantly formed by three cells and 6% of the clusters by four neurons. The distribution and the spatial arrangement of clusters are very regular, forming a mosaic that gives rise to a precise retinal coverage. The nearest-neighbor analysis unequivocally demonstrated that the mosaic of clusters is the most regular array so far described. This exact arrangement starts from 11 days of incubation and is maintained and refined through the following stages of development and after birth.

The visual arrestins in rhabdomeral photoreceptors are multifunctional phosphoproteins. They are rapidly phosphorylated in response to light, but the functional relevance of this phosphorylation is not yet fully understood. The phosphorylation of Limulus visual arrestin is particularly complex in that it becomes phosphorylated on three sites, and one or more of these site are phosphorylated even in the dark. The purpose of this study was to examine in detail the light-stimulated phosphorylation of each of the three sites in Limulus visual arrestin in intact photoreceptors. We found that light increased the phosphorylation of all three sites (S377, S381, and S396), that S381 is a preferred phosphorylation site, and that S377 and S381 are highly phosphorylated in the dark. The major effect of light was to increase the phosphorylation of S396, the site located closest to the C-terminal and very close to the adaptin binding motif. We speculate that the phosphorylation of this site may be particularly important for regulating the light-driven endocytosis of rhabdomeral membrane.

In the probed-sinewave paradigm—used to study the dynamics of light adaptation—a small probe of light is superimposed on a sinusoidally flickering background. Detection threshold for the probe is measured at various times with respect to the flickering background. Here we present such stimuli using three methods: monoptic (the probe and the flickering background are presented to the same eye), dichoptic (the probe is presented to one eye and the flickering background is presented to the other eye), and binocular (the probe and the flickering background are both presented to both eyes). The results suggest that the processing associated with detecting the probe is primarily in the retina (or any place with monocular input). However, the results also suggest a slight amount of processing in the cortex (or any place with binocular input), particularly at the higher frequency of flickering background used here (9.4 Hz vs. 1.2 Hz). A simple schematic model with three ocular-dominance channels is consistent with the results.

Autoradiography with 125I-neurotensin in normal and enucleated hamsters was used to define the distribution of receptors for this peptide in the superficial layers of the superior colliculus (SC). Neurotensin binding sites were densely distributed in the stratum griseum superficiale (SGS), and results from the enucleated animals indicated that they were not located on retinal axons. The effects of neurotensin on individual superficial layer cells were tested in single-unit recording experiments. Neurotensin was delivered via micropressure ejection during visual stimulation (n = 75 cells), or during electrical stimulation of either the optic chiasm (OX; n = 47 cells) or visual cortex (CTX; n = 29 cells). In comparison with control values, application of neurotensin decreased visual responses of all SC cells tested to 54.1 ± 34.9% (mean ± standard deviation; range of decrement 7.5 to 100%; nine cells showed no effect or an increase in visual activity, which for four of these was ≥30%). Neurotensin application also reduced responses to electrical stimulation of either OX or CTX, respectively, to 65.8 ± 36.5% of control values (range of decrement 2.6 to 97.4%; 12 neurons showed a weak increment ≤ 30%) and 68.0 ± 38.5% (range of decrement 3.3 to 100%; five cells showed no effect or an increment, in one case ≥ 30%). Of the 25 neurons tested with both OX and CTX stimulation, the correlation of evoked response suppression by neurotensin was highly significant (r = 0.70; P < 0.001). This suggests that the suppressive effects of neurotensin were common to both pathways. To test whether the inhibitory effects of neurotensin were presynaptic or postsynaptic, Mg2+ ions were ejected iontophoretically to abolish synaptic responses, and the neurons (n = 16) were activated by iontophoresis of glutamate and then tested with neurotensin. Neurotensin reduced the glutamate-evoked responses to an average 59.3 ± 37.9% of control values (range 2.3 to 92.5%; one cell showed an increment >30%). This result suggests that the site of action of neurotensin is most likely postsynaptic.