Research Article
Remembering Bob Rodieck: 1937–2003
- DAVID J. CALKINS
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- 06 October 2005, pp. 379-381
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In this special issue of Visual Neuroscience, we present a series of papers to honor the life and career of Robert William Rodieck, who passed away at his home in Seattle on September 30, 2003. Rodieck held the E.K. Bishop Professorship in Ophthalmology at the University of Washington Medical Center from 1978–1997. Known to everyone as “Bob,” he leaves behind an intellectual legacy often admired by his colleagues and friends for its scope, intensity, and empathy for what was beautiful in the object of his studies.
Wide-field ganglion cells in macaque retinas
- ELIZABETH S. YAMADA, ANDREA S. BORDT, DAVID W. MARSHAK
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- 06 October 2005, pp. 383-393
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To describe the wide-field ganglion cells, they were injected intracellularly with Neurobiotin using an in vitro preparation of macaque retina and labeled with streptavidin-Cy3. The retinas were then labeled with antibodies to choline acetyltransferase and other markers to indicate the depth of the dendrites within the inner plexiform layer (IPL) and analyzed by confocal microscopy. There were eight different subtypes of narrowly unistratified cells that ramified in each of the 5 strata, S1–5, including narrow thorny, large sparse, large moderate, large dense, large radiate, narrow wavy, large very sparse, and fine very sparse. There were four types of broadly stratified cells with dendritic trees extending from S4 to S2. One type resembled the parvocellular giant cell and another the broad thorny type described previously in primates. Another broadly stratified cell was called multi-tufted based on its distinctive dendritic branching pattern. The fourth type had been described previously, but not named; we called it broad wavy. There was a bistratified type with its major arbor in S5, the same level as the blue cone bipolar cell; it resembled the large, bistratified cell with blue ON-yellow OFF responses described recently. Two wide-field ganglion cell types were classified as diffuse because they had dendrites throughout the IPL. One had many small branches and was named thorny diffuse. The second was named smooth diffuse because it had straighter dendrites that lacked these processes. Dendrites of the large moderate and multi-tufted cells cofasciculated with ON-starburst cell dendrites and were, therefore, candidates to be ON- and ON–OFF direction-selective ganglion cells, respectively. We concluded that there are at least 15 morphoplogical types of wide-field ganglion cells in macaque retinas.
Mosaic properties of midget and parasol ganglion cells in the marmoset retina
- BRETT A. SZMAJDA, ULRIKE GRÜNERT, PAUL R. MARTIN
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- 06 October 2005, pp. 395-404
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We measured mosaic properties of midget and parasol ganglion cells in the retina of a New World monkey, the common marmoset Callithrix jacchus. We addressed the functional specialization of these populations for color and spatial vision, by comparing the mosaic of ganglion cells in dichromatic (“red–green color blind”) and trichromatic marmosets. Ganglion cells were labelled by photolytic amplification of retrograde marker (“photofilling”) following injections into the lateral geniculate nucleus, or by intracellular injection in an in vitro retinal preparation. The dendritic-field size, shape, and overlap of neighboring cells were measured. We show that in marmosets, both midget and parasol cells exhibit a radial bias, so that the long axis of the dendritic field points towards the fovea. The radial bias is similar for parasol cells and midget cells, despite the fact that midget cell dendritic fields are more elongated than are those of parasol cells. The dendritic fields of midget ganglion cells from the same (ON or OFF) response-type array show very little overlap, consistent with the low coverage of the midget mosaic in humans. No large differences in radial bias, or overlap, were seen on comparing retinae from dichromatic and trichromatic animals. These data suggest that radial bias in ganglion cell populations is a consistent feature of the primate retina. Furthermore, they suggest that the mosaic properties of the midget cell population are associated with high spatial resolution rather than being specifically associated with trichromatic color vision.
Horizontal cell morphology in nocturnal and diurnal primates: A comparison between owl-monkey (Aotus) and capuchin monkey (Cebus)
- SETSUKO N. DOS SANTOS, JOSÉ WESLEY L. DOS REIS, MANOEL DA SILVA FILHO, JAN KREMERS, LUIZ CARLOS L. SILVEIRA
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- 06 October 2005, pp. 405-415
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Horizontal cell morphology was studied in the retina of the nocturnal owl-monkey, Aotus, and compared with that of its diurnal, close relative, the capuchin monkey, Cebus. Cells were initially labeled with DiI and the staining was later photoconverted in a stable precipitated using DAB as chromogen. The sizes of cell bodies, dendritic fields, and axon terminals, number of dendritic clusters, intercluster spacing, and intercone spacing were measured at increasing eccentricities. Two distinct morphological classes of horizontal cells were identified, which resembled those of H1 and H3 cells described in diurnal monkeys. A few examples of a third class, possibly corresponding to the H2 cells of diurnal monkeys, were labeled. Both H1 and H3 cells increased in size and had increasing numbers of dendritic clusters with eccentricity. H3 cells were larger and had a larger number of dendritic clusters than H1 cells. Owl-monkey H1 cells had larger dendritic fields than capuchin monkey H1 cells at all quadrants in the central and midperipheral retinal regions, but the difference disappeared in the far periphery. Owl-monkey and capuchin monkey H1 cells had about the same number of dendritic clusters across eccentricity. As owl-monkey H1 cells were larger than capuchin monkey H1 cells, the equal number of clusters in these two primates was due to the fact that they were more spaced in the owl-monkey cells. H1 intercluster distance closely matched intercone spacing for both the owl-monkey and capuchin monkey retinas. On the other hand, H3 intercluster distance was larger than intercone spacing in the retina of both primates. Owl-monkey H1 axon terminals had 2–3 times more knobs than capuchin monkey H1 axon terminals in spite of having about the same size and, consequently, knob density was 2–3 times higher for owl-monkey than capuchin monkey H1 axon terminals across all eccentricities. The differences observed between owl-monkey and capuchin monkey horizontal cells, regarding the morphology of their dendritic trees and axon terminals, may be related to the differences found in the cone-to-rod ratio in the retina of these two primates. They seem to represent retinal specializations to the nocturnal and diurnal life styles of the owl-monkey and capuchin monkey, respectively.
Toward a unified model of vertebrate rod phototransduction
- R.D. HAMER, S.C. NICHOLAS, D. TRANCHINA, T.D. LAMB, J.L.P. JARVINEN
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- 06 October 2005, pp. 417-436
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Recently, we introduced a phototransduction model that was able to account for the reproducibility of vertebrate rod single-photon responses (SPRs) (Hamer et al., 2003). The model was able to reproduce SPR statistics by means of stochastic activation and inactivation of rhodopsin (R*), transducin (Gα), and phosphodiesterase (PDE). The features needed to capture the SPR statistics were (1) multiple steps of R* inactivation by means of multiple phosphorylations (followed by arrestin capping) and (2) phosphorylation dependence of the affinity between R* and the three molecules competing to bind with R* (Gα, arrestin, and rhodopsin kinase). The model was also able to account for several other rod response features in the dim-flash regime, including SPRs obtained from rods in which various elements of the cascade have been genetically disabled or disrupted. However, the model was not tested under high light-level conditions. We sought to evaluate the extent to which the multiple phosphorylation model could simultaneously account for single-photon response behavior, as well as responses to high light levels causing complete response saturation and/or significant light adaptation (LA). To date no single model, with one set of parameters, has been able to do this. Dim-flash responses and statistics were simulated using a hybrid stochastic/deterministic model and Monte-Carlo methods as in Hamer et al. (2003). A dark-adapted flash series, and stimulus paradigms from the literature eliciting various degrees of light adaptation (LA), were simulated using a full differential equation version of the model that included the addition of Ca2+-feedback onto rhodopsin kinase via recoverin. With this model, using a single set of parameters, we attempted to account for (1) SPR waveforms and statistics (as in Hamer et al., 2003); (2) a full dark-adapted flash-response series, from dim flash to saturating, bright flash levels, from a toad rod; (3) steady-state LA responses, including LA circulating current (as in Koutalos et al., 1995) and LA flash sensitivity measured in rods from four species; (4) step responses from newt rods (Forti et al., 1989) over a large dynamic range; (5) dynamic LA responses, such as the step-flash paradigm of Fain et al. (1989), and the two-flash paradigm of Murnick and Lamb (1996); and (6) the salient response features from four knockout rod preparations. The model was able to meet this stringent test, accounting for almost all the salient qualitative, and many quantitative features, of the responses across this broad array of stimulus conditions, including SPR reproducibility. The model promises to be useful in testing hypotheses regarding both normal and abnormal photoreceptor function, and is a good starting point for development of a full-range model of cone phototransduction. Informative limitations of the model are also discussed.
Response of the difference-of-Gaussians model to circular drifting-grating patches
- G.T. EINEVOLL, H.E. PLESSER
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- 06 October 2005, pp. 437-446
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Forty years ago R.W. Rodieck introduced the Difference-of-Gaussians (DOG) model, and this model has been widely used by the visual neuroscience community to quantitatively account for spatial response properties of cells in the retina and lateral geniculate nucleus following visual stimulation. Circular patches of drifting gratings are now regularly used as visual stimuli when probing the early visual system, but for this stimulus type the mathematical evaluation of the DOG-model response is significantly more complicated than for moving bars, full-field drifting gratings, or circular flashing spots. Here we derive mathematical formulas for the DOG-model response to centered circular patch gratings. The response is found to be given as the difference between two summed series, where each term in the series involves the confluent hypergeometric function. This function is available in commonly used mathematical software, and the results should thus be readily applicable. Example results illustrate how a strong surround suppression in area-summation curves for iso-luminant circular spots may be reversed into a surround enhancement for circular patch gratings. They also show that the spatial-frequency response changes from band-pass to low-pass when going from the full-field grating situation to the situation where the patch covers only the receptive-field center.
Gradients of cone differentiation and FGF expression during development of the foveal depression in macaque retina
- ELISA E. CORNISH, MICHELE C. MADIGAN, RICCARDO NATOLI, ANGELA HALES, ANITA E. HENDRICKSON, JAN M. PROVIS
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- 06 October 2005, pp. 447-459
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Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones—in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to study cone elongation on the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1–4 at the developing fovea, and three other sample locations on the horizontal meridian. Labeled RNA was detected using the fluorescent marker “Fast Red” (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.
Regularity and packing of the horizontal cell mosaic in different strains of mice
- MARY A. RAVEN, STEPHANIE B. STAGG, BENJAMIN E. REESE
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- 06 October 2005, pp. 461-468
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The present study describes the relationships between mosaic regularity, intercellular spacing, and packing of horizontal cells across a two-fold variation in horizontal cell density in four strains of mice. We have tested the prediction that mosaic patterning is held constant across variation in density following our recent demonstration that intercellular spacing declines as density increases, by further examination of that dataset: Nearest-neighbor and Voronoi-domain analyses were conducted on multiple fields of horizontal cells from each strain, from which their respective regularity indices were calculated. Autocorrelation analysis was performed on each field, from which the density recovery profile was generated, and effective radius and packing factor were calculated. The regularity indexes showed negative correlations with density rather than being held constant, suggesting that the strong negative correlation between intercellular spacing and density exceeded that required to produce a simple scaling of the mosaic. This was confirmed by the negative correlation between packing factor and density. These results demonstrate that the variation in the patterning present in the population of horizontal cells across these strains is a consequence of epigenetic mechanisms controlling intercellular spacing as a function of density.
Localization of ionotropic glutamate receptors to invaginating dendrites at the cone synapse in primate retina
- DAVID J. CALKINS
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- 06 October 2005, pp. 469-477
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The separation of OFF pathways that signal light decrements from ON pathways that signal light increments occurs at the first retinal synapse. The dendrites of OFF bipolar cells abut the cone pedicle at basal positions distal to the site of glutamate release and express ligand-gated or ionotropic glutamate receptors (GluR). The dendrites of ON bipolar cells penetrate narrow invaginations of the cone pedicle proximal to the site of release and express the G-protein-coupled, metabotropic glutamate receptor, mGluR6. However, recent studies demonstrating the expression of GluR subunits in the rodent rod bipolar cell, known to yield an ON response to light, call this basic segregation of receptors into question. The light-microscopic distribution of many glutamate receptors in the primate retina is now well established. We reexamined their ultrastructural localization in the outer retina of Macaca fascicularis to test systematically whether invaginating dendrites at the cone synapse, presumably from ON bipolar cells, also express one or more ionotropic subunits. Using preembedding immunocytochemistry for electron microscopy, we quantified the distribution of the AMPA-sensitive subunits GluR2/3 and GluR4 and of the kainate-sensitive subunits GluR6/7 across 207 labeled dendrites occupying specific morphological loci at the cone pedicle. We report, in agreement with published investigations, that the majority of labeled processes for GluR2/3 (70%) and GluR4 (67%) either occupy basal positions or arise from horizontal cells. For GluR6/7, we find a significantly lower fraction of labeled processes at these positions (47%). We also find a considerable number of labeled dendrites for GluR2/3 (10%), GluR4 (21%), and GluR6/7 (18%) at invaginating positions. Surprisingly, for each subunit, the remainder of labeled processes corresponds to “fingers” of presynaptic cytoplasm within the cone invagination.
Spatial coding and response redundancy in parallel visual pathways of the marmoset Callithrix jacchus
- JASON D. FORTE, MAZIAR HASHEMI-NEZHAD, WILLIAM J. DOBBIE, BOGDAN DREHER, PAUL R. MARTIN
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- 06 October 2005, pp. 479-491
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Many neurons in the primary visual cortex (area V1) show pronounced selectivity for the orientation and spatial frequency of visual stimuli, whereas most neurons in subcortical afferent streams show little selectivity for these stimulus attributes. It has been suggested that this transformation is a functional sign of increased coding efficiency, whereby the redundancy (or overlap in response properties) is reduced at consecutive levels of visual processing. Here we compared experimentally the response redundancy in area V1 with that in the three main dorsal thalamic afferent streams, the parvocellular (PC), koniocellular (KC), and magnocellular (MC) divisions of the dorsal lateral geniculate nucleus (LGN) in marmosets. The spatial frequency and orientation tuning of single cells in the LGN and area V1 were measured, using luminance contrast sine-wave gratings. A joint spatial frequency-orientation response selectivity profile was calculated for each cell. Response redundancy for each population was estimated by cross-multiplication of the joint selectivity profiles for pairs of cells. We show that when estimated in this way, redundancy in LGN neurons is approximately double that of neurons in cortical area V1. However, there are differences between LGN subdivisions, such that the KC pathway has a spatial representation that lies between the redundant code of the PC and MC pathways and the more efficient sparse spatial code of area V1.
Spatiotemporal integration of light by the cat X-cell center under photopic and scotopic conditions
- J.B. TROY, D.L. BOHNSACK, J. CHEN, X. GUO, C.L. PASSAGLIA
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- 06 October 2005, pp. 493-500
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Visual responses to stimulation at high temporal frequency are generally considered to result from signals that avoid light adaptive gain adjustment, simply reflecting linear summation of luminance. Under conditions of high photopic illuminance, the center of the receptive field of the cat X-cell has been shown to expand in size when stimulated at high temporal frequency, raising the possibility that there is spatiotemporal interaction in luminance summation. Here we show that this expansion maintains constant the product of the center's luminance summing area and the temporal period of luminance modulation, implying that spatial and temporal integration of luminance can be traded for one another by the X-cell center. As such the X-cell has a spatiotemporal window for luminance integration that fuses the classical concepts of a spatial window of luminance integration (Ricco's Law) with a temporal window of luminance integration (Bloch's Law). We were interested to determine whether this tradeoff between spatial and temporal summation of luminance occurs also at lower light levels, where the temporal-frequency bandwidth of the X-cell is narrower. We found that it does not. Center radius does not expand with temporal frequency under either low photopic or scotopic conditions. These results are discussed within the context of the known retinal circuitry that underlies the X-cell center for photopic and scotopic conditions.
Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia
- JOHN WELLARD, DONALD LEE, KRISZTINA VALTER, JONATHAN STONE
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- 06 October 2005, pp. 501-507
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The current study aims to assess the vulnerability of photoreceptors in rat retina to variations in tissue oxygen levels. Young adult Sprague-Dawley rats were exposed to air with the concentration of oxygen set at 10% (hypoxia), 21% (room air, normoxia), and four levels of hyperoxia (45%, 65%, 70%, and 75%), for up to 3 weeks. Their retinas were then examined for cell death, using the TUNEL technique. Hypoxia (10% oxygen) for 2 weeks caused a limited but significant rise in the frequency of TUNEL+ (dying) cells in the retina, the great majority (> 90%) being located in the outer nuclear layer (ONL). Hyperoxia also induced an increase in the frequency of TUNEL+ cells, again predominantly in the ONL. The increase rose with duration of exposure, up to 2 weeks. At 2 weeks exposure, the increase was limited yet significant at 45% oxygen, and maximal at 65%. Where the frequencies of TUNEL+ cells were high, it was evident that photoreceptor death was maximal in the midperipheral retina. The adult retina is vulnerable to maintained shifts in oxygen availability to the retina, both below and above normal. The vulnerability is specific to photoreceptors; other retinal neurons appeared resistant to the exposures tested. Shifts in retinal oxygen levels caused by variations in ambient light, by the persistence of light through the normally dark (night) half of the day–night cycle, or by depletion of the photoreceptor population, may contribute to photoreceptor death in the normal retina.
“Small-tufted” ganglion cells and two visual systems for the detection of object motion in rabbit retina
- E.V. FAMIGLIETTI
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- 06 October 2005, pp. 509-534
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Small-tufted (ST) ganglion cells of rabbit retina are divided into eight types based upon morphology, branching pattern, level of dendritic stratification, and quantitative dimensional analysis. Only one of these types has been previously characterized in Golgi preparations, and four may be discerned in the work of others. Given their small dendritic-field size, and assuming uniform mosaics of each across the retina, ST cells comprise about 45% of all rabbit ganglion cells, and are therefore of major functional significance. Four ST cells occur as two paramorphic (a/b) pairs, and thus belong to class III, as previously defined. Four branch in sublaminae a and b of the inner plexiform layer (IPL) and therefore belong to class IV. ST cells have small cell bodies 10–15 μm in diameter, small axons 0.7–1.3 μm in diameter, and small dendritic-field diameters, 40–110 μm in mid-visual streak. The dendrites of ST cells are highly branched, and bear spines and appendages of varying length, but vary from type to type. Class III.2 cells and class III.3 cells are partly bistratified. Class IV small-tufted cells differ characteristically in multiple features of dendritic branching and stratification. Class III small-tufted cells apparently have concentric (ON-center and OFF-center) receptive fields and may have “sluggish-transient” (class III.2) and “sluggish-sustained” (class III.3) physiology. Class IV cells include the “local-edge-detector” (LED) (class IVst1), and are all expected to give ON–OFF responses to small, centered, slowly moving visual stimuli. Based upon systematic variation in dendritic-field size across the retina, ST cells may be divided into two groups. In this “universal prey” species, they may belong to two systems of motion detection, typified by ON–OFF directionally selective and LED ganglion cells, respectively, specialized for detection of rapid motion at the horizon for land-based predators, and slow motion for airborne predators.
Stratification of alpha ganglion cells and ON/OFF directionally selective ganglion cells in the rabbit retina
- JIAN ZHANG, WEI LI, HIDEO HOSHI, STEPHEN L. MILLS, STEPHEN C. MASSEY
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- 06 October 2005, pp. 535-549
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The correlation between cholinergic sensitivity and the level of stratification for ganglion cells was examined in the rabbit retina. As examples, we have used ON or OFF α ganglion cells and ON/OFF directionally selective (DS) ganglion cells. Nicotine, a cholinergic agonist, depolarized ON/OFF DS ganglion cells and greatly enhanced their firing rates but it had modest excitatory effects on ON or OFF α ganglion cells. As previously reported, we conclude that DS ganglion cells are the most sensitive to cholinergic drugs. Confocal imaging showed that ON/OFF DS ganglion cells ramify precisely at the level of the cholinergic amacrine cell dendrites, and co-fasciculate with the cholinergic matrix of starburst amacrine cells. However, neither ON or OFF α ganglion cells have more than a chance association with the cholinergic matrix. Z-axis reconstruction showed that OFF α ganglion cells stratify just below the cholinergic band in sublamina a while ON α ganglion cells stratify just below cholinergic b. The latter is at the same level as the terminals of calbindin bipolar cells. Thus, the calbindin bipolar cell appears to be a prime candidate to provide the bipolar cell input to ON α ganglion cells in the rabbit retina. We conclude that the precise level of stratification is correlated with the strength of cholinergic input. Alpha ganglion cells receive a weak cholinergic input and they are narrowly stratified just below the cholinergic bands.