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The center–surround organization of the receptive fields (RFs) of retinal ganglion cells highlights the presence of local contrast in visual stimuli. As RF of thalamic relay cells follow the same basic functional organization, it is often assumed that they contribute very little to alter the retinal output. However, in many species, thalamic relay cells largely outnumber their retinal inputs, which diverge to contact simultaneously several units at thalamic level. This gain in cell population as well as retinothalamic convergence opens the door to question how information about contrast is transformed at the thalamic stage. Here, we address this question using a realistic dynamic model of the retinothalamic circuit. Our results show that different components of the thalamic RF might implement filters that are analogous to two types of well-known image processing techniques to preserve the quality of a higher resolution version of the image on its way to the primary visual cortex.
Color plays a key role in human vision but the neural machinery that underlies the transformation from stimulus to perception is not well understood. Here, we implemented a two-dimensional network model of the first stages in the primate parvocellular pathway (retina, lateral geniculate nucleus and layer 4Cβ in V1) consisting of conductance-based point neurons. Model parameters were tuned based on physiological and anatomical data from the primate foveal and parafoveal vision, the most relevant visual field areas for color vision. We exhaustively benchmarked the model against well-established chromatic and achromatic visual stimuli, showing spatial and temporal responses of the model to disk- and ring-shaped light flashes, spatially uniform squares and sine-wave gratings of varying spatial frequency. The spatiotemporal patterns of parvocellular cells and cortical cells are consistent with their classification into chromatically single-opponent and double-opponent groups, and nonopponent cells selective for luminance stimuli. The model was implemented in the widely used neural simulation tool NEST and released as open source software. The aim of our modeling is to provide a biologically realistic framework within which a broad range of neuronal interactions can be examined at several different levels, with a focus on understanding how color information is processed.
The mammalian retina extracts a set of 12 different "movies" from the visual scene and send each movie to higher visual centers. These movies exist in physically distinct strata of the inner retina, embodied in the dendritic arborizations of a dozen different ganglion cell types. The dendritic arbors are stacked in discrete layers throughout the inner retina where they are synaptically contacted by excitatory and inhibitory connections from a variety of different cell types. This paper outlines the synaptic and physical structure of these layers, and follows the image of a face through the retina from photoreceptors to final output, graphically displaying the transformations that take place as the image is processed by different neural structures.
The article is about drug delivery to the retina. It discusses about the various types of drug delivery to the retina.
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The chronic and uncontrolled diabetes mellitus (DM) damages the retinal blood vessels leading to diabetic retinopathy (DR). The advanced stage of DR leads to loss of vision and subsequently blindness. The morphological changes during the progression of DR can be diagnosed using digital fundus images. The pathological changes in the retina influence the variations in pixel patterns which can be quantified using texture measures. In this paper, we have explored different texture measures namely statistical moments, gray level co-occurrence matrix (GLCM), gray level run length matrix (GLRLM), local binary pattern (LBP), laws mask energy (LME), fractal dimension (FD), fourier spectrum (FS) and Gabor wavelet to characterize and classify the normal and DR classes. We have tabulated 109 texture parameters for the normal and DR classes. Further, these features were subjected to empirical receiver operating characteristic (ROC) based ranking to select optimal feature set. The ranked nested features were fed to the support vector machine (SVM) classifier with different kernel functions to evaluate the highest performance measure using the least number of features to discriminate normal and DR classes. Our proposed system was evaluated using two different databases Kasturba Medical College Hospital (KMCH) and Tan Tock Seng Hospital (TTSH), each with 340 images (170 normal and 170 DR). We have also formulated an integrated index called as diabetic retinopathy risk index (DRRI) using selected texture features to discriminate normal and DR classes using single number. The proposed frame work can be used to help the clinicians and also for mass DR screening programs.
The elevated intraocular pressure (IOP) is one of the important risk factors of glaucomatous optic nerve damage. The deformations of glaucomatous optic nerve head (ONH) due to the elevated IOP might lead to further damage to the optic nerve. The ONH deformations due to the elevated IOP depend on their geometry. Therefore, it is meaningful to investigate the relationship between geometrical parameters and the deformation of ONH. Firstly, the geometrical parameters of ONH were obtained by in vivo using spectral domain optical coherence tomography. Then, individual-specific three-dimensional (3D) models of ONH for glaucoma and normal subjects were established and the deformations of ONH were acquired by using finite element method. Furthermore, the thickness changes of retina and lamina cribrosa were calculated under different IOPs. Finally, correlations between geometrical parameters and the relative deformations of the human ONH were researched by using Spearman correlation. It was found that the relative thickness change of patient’s retina was larger than that of normal subjects under the same condition. The correlation of several parameters, including cup area, and lamina cribrosa depth, with relative deformations of ONH had statistical significance.
Previously we reported that cultured rat GABAergic amacrine cells can evoke subthreshold graded depolarization and action potentials. Both types of electrical signals are thought to contribute to neurotransmitter release from their dendrites, because Ca2+ channels in amacrine cells can be activated at a subthreshold level (around -50mV). The aim of the present study is to describe the spatiotemporal pattern of the spread of these electrical signals in an amacrine cell, using a computer simulation study. The simulation is based on physiological data, obtained by dual whole-cell patch-clamp recordings on the soma and the dendrites of cultured rat GABAergic amacrine cells. We determined passive and active properties of amacrine cells from the physiological recordings. Then, using the NEURON simulator, we conducted computer simulations on a reconstructed model of amacrine cells. We show that graded potentials and action potentials spread through amacrine cells with distinct patterns, and discuss the electrical interrelationship among the dendrites of an amacrine cell. Subthreshold graded potentials applied to a distal dendrite were sufficiently localized, so that each dendrite could behave independently (dendritic independence). However, at a suprathreshold level, once action potentials were triggered, they propagated into every dendrite, exciting the entire cell (dendritic interdependence). We also showed that GABAergic inhibitory inputs on the dendrites suppress the dendritic interdependence of amacrine cells. These results suggest that an inhibitory amacrine cell can mediate both local and wide-field lateral inhibition, regulated by the spatiotemporal pattern of excitatory and inhibitory synaptic inputs on its dendrites.
Retinal amacrine cells regulate activities of retinal ganglion cells, the output neurons to higher visual centers, through cellular mechanism of lateral inhibition in the inner plexiform layer (IPL). Electrical properties of gap junction networks between amacrine cells in the IPL were investigated using combined techniques of intracellular recordings, Lucifer yellow and Neurobiotin injection, dual patch-clamp recordings and high voltage electron microscopy in isolated retinas of cyprinid fish. Six types of gap-junctionally connected amacrine cells were classified after their light-evoked responses to light flashes were recorded. Among them, gap junction networks of three types of amacrine cells were studied with structure-function correlation analysis. Cellular morphology of intercellular connections between three homologous cell classes was characterized. The interconnections between laterally extending dendrites in the IPL were localized at dendritic tip terminals. Three types of cells presented the dendrodendritic connections of tip-contact manner in the homologous cell population. High voltage as well as conventional electron microscopy revealed gap junctions between the dendritic tips of Neurobiotin-coupled cells. Receptive field properties of these amacrine cells were examined, displacing a slit of light along the distance from recording sites in the dorsal intermediate region of the retina. Receptive field size, space length constant, response latency and conduction velocity were measured. Spatial and temporal properties of receptive fields were symmetric along horizontally expanding dendrites in the dorsal retina. Simultaneous dual patch-clamp recordings revealed that the lateral gap junction connections between homologous amacrine cells expressed bidirectional electrical synapses passing Na+ spikes. These results demonstrate that bidirectional electrical transmission in gap junction networks of these amacrine cells is symmetric along the lateral gap junction connections between horizontally extending dendrites. Lateral inhibition regulated by amacrine cells in the IPL appears to be associated with the directional extension of the dendrites and the orientation of dendrodendritic gap junctions.
In this study, a bio-inspired approach for extracting efficient features prior to the recognition of scenes is proposed. It is highly inspired from the model of the mammals visual system. The retina contains many levels of neurons (bipolar, amacrine, horizontal and ganglion cells) accurately organized from cones and rods to the optic nerve up till the lateral geniculate nucleus (LGN) which is the main thalamic relay for inputs to the visual cortex. This structure probably eases other brain areas tasks in preprocessing the visual information. This paper is focusing on the study of these specific structures, relying on a bottom up approach to propose a comprehensive mathematical model of the low level image processing performed within the eye. The presented system takes into account the foveolar structure of the retina to produce a low-resolution representation of observed images by decomposing them into a local summation of elementary gaussian color histograms. This representation corresponds to the LGN biological organization. It has been thought that due to short timings, some very quick localization tasks involving particularly fast information processing pathways cannot be provided by the classical ones passing through higher level cortical areas. This work proposes a model of retinal coding and LGN-visual representation that we show provides reliable and sufficient early features for scenes recognition and localization. Experiments on real scenes using the developed model are presented showing the efficiency of the approach on localization.
Gap junctions are intercellular channels composed of subunit protein connexin and subserve electrotonic transmission between connected neurons. Retinal amacrine cells, as well as horizontal cells of the same class, are homologously connected by gap junctions. The gap junctions between these neurons extend their receptive fields, and may increase the inhibitory postsynaptic effects in the retina. In the present study, we investigated whether gap junctions between the neurons are modulated by internal messengers. The permeability of gap junctions was examined by the diffusion of intracellularly injected biotinylated tracers, biocytin or Neurobiotin, into neighboring cells since gap junctions are permeable to these molecules freely. 4% Lucifer Yellow and 6% biocytin or Neurobiotin were injected intracellularly into horizontal cells and amacrine cells in isolated retinas of carp and goldfish and Japanese dace following electrophysiological identification. In the control condition, the tracer spread into many neighboring cells from the recorded cells. Superfusion of retinas with dopamine (100 μM) suppressed diffusion of the tracer into the neighboring horizontal cells, but not in the case of amacrine cells. Intracellular injection of cyclic AMP (300 mM) completely blocked diffusion of the tracer into neighboring horizontal cells and amacrine cells. However, superfusion of retinas with 8-bromo-cyclic AMP (2 mM), membrane permeable cyclic AMP analog, permitted the tracer to diffuse into the neighboring horizontal cells or amacrine cells. Intracellular injection of cyclic GMP (300 mM) blocked the diffusion between neighboring horizontal cells, but did not suppress the diffusion between amacrine cells. These results show that the permeability of gap junctions between amacrine cells is regulated by high concentration of intracellular cyclic AMP level, but not for intracellular cyclic GMP or applied dopamine or extracellularly applied low concentrations of intracellular cyclic AMP level. The present study suggests that these laterally oriented inhibitory interneurons, horizontal cells and amacrine cells, express different connexins which may be differentially regulated by intercellular messengers.
A reaction-diffusion model is presented to encapsulate calcium-induced calcium release (CICR) as a potential mechanism for somatofugal bias of dendritic calcium movement in starburst amacrine cells. Calcium dynamics involves a simple calcium extrusion (pump) and a buffering mechanism of calcium binding proteins homogeneously distributed over the plasma membrane of the endoplasmic reticulum within starburst amacrine cells. The system of reaction-diffusion equations in the excess buffer (or low calcium concentration) approximation are reformulated as a nonlinear Volterra integral equation which is solved analytically via a regular perturbation series expansion in response to calcium feedback from a continuously and uniformly distributed calcium sources. Calculation of luminal calcium diffusion in the absence of buffering enables a wave to travel at distances of 120 μm from the soma to distal tips of a starburst amacrine cell dendrite in 100 msec, yet in the presence of discretely distributed calcium-binding proteins it is unknown whether the propagating calcium wave-front in the somatofugal direction is further impeded by endogenous buffers. If so, this would indicate CICR to be an unlikely mechanism of retinal direction selectivity in starburst amacrine cells.
In this paper, we found that spatial and temporal asymmetricity of excitatory connections are able to generate directional selectivity which can be enhanced by asymmetrical inhibitory connections by reconstructing a hexagonally-arranged three-layered simulation model of retina by NEURON simulator. Asymmetric excitatory inputs to ganglion cells with randomly arborizing dendrites were able to generate weaker directional selectivity to moving stimuli whose speed was less than 10 μm/msec. By just adding asymmetric inhibitory connections via inhibitory amacrine cells, directional selectivity became stronger to respond to moving stimuli at ten times faster speed (< 100 μm/msec). In conclusion, an excitatory mechanism appeared to generate directional selectivity while asymmetric inhibitory connections enhance directional selectivity in retina.
Fish have highly developed vision that plays an important role in detecting and recognizing objects in different forms of visually guided behavior. All of these behaviors require high spatial resolution. The theoretical limit of spatial resolution is determined by the optics of the eye and the density of photoreceptors. However, further in the fish retina, each bipolar cell may collect signals from tens of photoreceptors, and each ganglion cell may collect signals from tens to hundreds of bipolar cells. If we assume that the input signals in this physiological funnel are simply summed, then fine gratings that are still distinguishable at the level of cones should not differ from the homogeneous surface for the ganglion cells. It is therefore generally considered that the resolution of the eye is determined not by the density of cones, but by the density of ganglion cells. Given the size of the receptive field of ganglion cells, one can conclude that the resolving power at the output of the fish retina should be ten times worse than at its input. But this contradicts the results of behavioral studies, for, as it is known, fish are able to distinguish periodic gratings at the limit of resolution of the cones. Our electrophysiological studies with extracellular recording of responses of individual ganglion cells to the motion of contrast gratings of different periods showed that the acuity of ganglion cells themselves is much higher and is close to the limit determined by the density of cones. The contradiction is explained by the fact that ganglion cells are not linear integrators of the input signals, their receptive fields being composed of subunits with significantly smaller zones of signal summation where nonlinear retinal processing takes place.
Responses of direction-selective and orientation-selective motion detectors were recorded extracellularly from the axon terminals of ganglion cells in the superficial layers of the tectum opticum of immobilized goldfish, Carassius gibelio (Bloch, 1782). Color stripes or edges moving on some color background (presented on the CRT monitor with known emission spectra of its phosphors) served as stimuli. It was shown that stimuli of any color can be more or less matched with the background by varying their intensities what is indicative of color blindness of the motion detectors. Sets of stimuli which matched the background proved to represent planes in the three-dimensional color space of the goldfish. A relative contribution of different types of cones to the spectral sensitivity was estimated according to orientation of the plane of color matches. The spectral sensitivity of any motion detector was shown to be determined mainly by long-wave cones with a weak negative (opponent) contributions of middle-wave and/or short-wave ones. This resulted in reduced sensitivity in the blue–green end of the spectrum, what may be considered as an adaptation to the aquatic environment where, because of the substantial light scattering of a blue–green light, acute vision is possible only in a red region of the spectrum.
The output units of fish retina, i.e., the retinal ganglion cells (detectors), send highly processed information to the primary visual centers of the brain, settled in the midbrain formation tectum opticum (TO). Axons of different fish motion detectors terminate in different tectal levels. In the superficial layer of TO, axons of direction-selective ganglion cells (DS GCs) are terminated. Single unit responses of the DS GCs were recorded in intact fish from their axon terminals in TO. Goldfish DS GCs projecting to TO were shown to comprise six physiological types according to their selectivity to sign of stimulus contrast (ON and OFF units) and their preferred directions: three directions separated by 120∘. These units, characterized by relatively small receptive fields and remarkable spatial resolution should be classified as local motion detectors. In addition to the retinal DS GCs, other kinds of DS units were extracellularly recorded in the superficial and deep sublaminae of tectum. Some features of their responses suggested that they originated from tectal neurons (TNs). Contrary to DS GCs which are characterized by small RFs and use separate ON and OFF channels, DS TNs have extra-large RFs and ON-OFF type responses. DS TNs were shown to select four preferred directions. Three of them are compatible with those already selected on the retinal level. Complementary to them, the fourth DS TN type with rostro-caudal preference (lacking in the retina) has been revealed. Possible functional interrelations between DS GCs and DS TNs are discussed.
Sensitivity to the sign of contrast of direction-selective (DS) and orientation-selective (OS) ganglion cells (GCs) was investigated with selective stimulation of different chromatic types of cones. It was shown that the DS GCs that were classified with the use of achromatic stimuli as belonging to the ON type responded to selective stimulation of the long-wave cones as the ON type also, while the stimulation of middle-wave or short-wave cones elicited the OFF type responses. Character of the responses of DS GCs of the OFF type was exactly the opposite. OS GCs, which responded to achromatic stimuli as the ON–OFF type, responded to selective stimulation of the long-wave cones as the ON–OFF type as well, responded to middle-wave stimulation as the OFF type and to stimulation of short-wave cones it responded mainly as the ON type. At the same time, under color-selective stimulation, both DS and OS GCs retained the directional and orientation selectivity with the same preferred directions. The results obtained are in favor of the idea that the signals from the different chromatic types of cones are combined in the outer synaptic layer of the retina at the inputs of bipolar cells using sign-inverting and/or sign-conserving synapses, while specific spatial properties of motion detectors are formed in the inner synaptic layer.
Interactions between color channels (long-wave (L), middle-wave (M) and short-wave (S)) in the receptive field of direction-selective (DS) and orientation-selective (OS) ganglion cells (GCs) were investigated with combined selective stimulation of pairs of cone types (L and M, L and S, M and S). In the experiments with DS GCs of both ON and OFF types, it was shown that: (1) M and S channels were synergistic relative to each other and opponent to L channel. (2) Three-parameter signal (from L, M and S cones) is transformed to one-parameter signal at the output of DS GC, thus illustrating the principle of univariance. (3) In the experiments with OS GCs, it was shown that L and M channels were synergistic in the OFF-pathway, while the S channel was opponent to them. Our results suggested that photoreceptor synaptic connectivity of the bipolar cells hypothetically involved in the goldfish OS circuitry substantially differs from connectivity of bipolar cells presumably targeting DS GC. (4) To sum up, the results obtained on DS GCs confirmed the plausibility of proposed DS GC wiring diagrams; as to the OS circuitry of fish retina it still remains unclear and needs further investigation.
The vertebrate visual system is determined by two main factors, a species’ lifestyle and phylogenetic legacy. Studying the visual system in outgroup lineages may shed some light on the balance of these factors within a certain radiation. We studied the topography of retinal ganglion cells (RGCs) in the retina of the oriental fire-bellied toad Bombina orientalis. These toads belong to the ancient superfamily Discoglossoidea, a sister group to all extant Anura except for two small families. RGCs were retrogradely labeled with tetramethylrhodamine– dextran amine (TMR-DA) and examined in retinal wholemounts. RGCs occurred all over the retina except for the far periphery. Their total number was 214.42±14.49×103 (mean±SEM, N=5). They comprised 73–77% of all cells in the ganglion cell layer. The spatial density of GCs increased gradually from the dorsal and ventral retinal periphery toward the equator to form a weak visual streak and a moderately pronounced area centralis. The minimum density was 5.42±0.15, and the maximum, 14.92±0.52cells∕mm2. The maximum density gradient was 2.76±0.14. The spatial resolution was minimum in the dorsal and ventral periphery (3.68±0.05 and 2.77±0.04 cycles per degree in water and air, respectively). Intermediate values of spatial resolving power were found within the visual streak (5.38±0.06 and 4.05±0.05 cycles per degree) and reached a peak in area centralis (6.11±0.11 and 4.59±0.08 cycles per degree). This is sufficient for efficient prey location and capture. The relatively high RGC density and the presence of specialized retinal regions in oriental fire-bellied toads are consistent with their highly visual behavior. A brief review comparing the phylogeny and ecology of this with other anuran species suggests that the main factor shaping the RGC distribution in Anura is phylogenetic legacy; the environmental pressure results mainly in adjusting the maximum spatial density of RGCs (and hence the visual acuity) to meet the species’ needs.