Research Article
Visual evoked potentials for red–green gratings reversing at different temporal frequencies: Asymmetries with respect to isoluminance
- INGER RUDVIN, ARNE VALBERG
-
- Published online by Cambridge University Press:
- 03 February 2006, pp. 735-747
-
- Article
- Export citation
-
Human visual evoked potentials (VEPs) were recorded for abrupt reversals of 2 cycles/deg (c/deg) square-wave gratings combining high red–green contrast with different levels of luminance contrast. Response characteristics—2nd harmonic amplitudes and peak latencies as a function of luminance contrast—were compared for four different reversal rates ranging from 6.25 Hz to 12.5 Hz. At every reversal frequency, the VEP amplitude and latency plots were nonsymmetrical with respect to isoluminance. The amplitude dropped to a minimum within a region of rapid phase change, always at a red–green luminance contrast for which the green color had the higher luminance, at about 40% or 50% Michelson luminance contrast. The rapid phase shift around this contrast suggested a sudden change in the relative impact of VEP generators with different latencies, possibly dominated by parvocellular or magnocellular input. The most prominent VEP waveform through most of the luminance contrast range, P110, is interpreted in terms of a parvo-mediated response that is attenuated with increasing reversal frequency. Contrast-dependent changes in the P110 amplitude appear to be responsible for the VEP asymmetries reported here.
Contrast response of temporally sparse dichoptic multifocal visual evoked potentials
- TED MADDESS, ANDREW CHARLES JAMES, ELIZABETH ANNE BOWMAN
-
- Published online by Cambridge University Press:
- 02 June 2005, pp. 153-162
-
- Article
- Export citation
-
Temporally sparse stimuli have been found to produce larger multifocal visual evoked potentials than rapid contrast-reversal stimuli. We compared the contrast-response functions of conventional contrast-reversing (CR) stimuli and three grades of temporally sparse stimuli, examining both the changes in response amplitude and signal-to-noise ratio (SNR). All stimuli were presented dichoptically to normal adult human subjects. One stimulus variant, the slowest pattern pulse, had interleaved monocular and binocular stimuli. Response amplitudes and SNRs were similar for all stimuli at contrast 0.4 but grew faster with increasing contrast for the sparser stimuli. The best sparse stimulus provided an SNR improvement that corresponded to a recording time improvement of 2.6 times relative to that required for contrast reversing stimuli. Multiple regression of log-transformed response metrics characterized the contrast-response functions by fitting power-law relationships. The exponents for the two sparsest stimuli were significantly larger (P < 0.001) than for the CR stimuli, as were the mean response amplitudes and signal-to-noise ratios for these stimuli. The contrast-dependent response enhancement is discussed with respect to the possible influences of rapid retinal contrast gain control, or intracortical and cortico-geniculate feedback.
MEG recording from the human ventro-occipital cortex in response to isoluminant color stimulation
- ICHIRO KURIKI, KENJI SADAMOTO, TSUNEHIRO TAKEDA
-
- Published online by Cambridge University Press:
- 02 August 2005, pp. 283-293
-
- Article
- Export citation
-
In contrast to PET and fMRI studies, color-selective responses from the ventro-occipital area have rarely been reported in MEG studies. We tried to minimize the stimulation to all areas in the visual system except the color-processing ones by using a color space based on psychophysical and physiological knowledge in order to maximize the signal-to-noise ratio for MEG responses from the ventro-occipital area. MEG obtained from long intermittent reversals (2.0–3.5 s) of isoluminant chromatic gratings showed two major peaks at the latencies of approximately 100 and 150 ms. The estimated location of the equivalent-current dipole for response at 100-ms latency was in the calcarine sulcus and that of the dipole for the response at 150 ms was in the collateral sulcus in the ventro-occipital area. The response around 150 ms was uniquely observed in MEG elicited by chromatic reversals. The average of lags between MEG responses from the calcarine sulcus and ventro-occipital area was 43 ms, which suggests sequential processing of color information across the visual cortices.
Unilateral photoreceptor rescue can improve the ability of the opposite, untreated, eye to drive cortical cells in a retinal degeneration model
- S.V. GIRMAN, R.D. LUND
-
- Published online by Cambridge University Press:
- 05 April 2005, pp. 37-43
-
- Article
- Export citation
-
In the Royal College of Surgeons, rat photoreceptor degeneration occurs over the first several months of life, causing deterioration of visual cortical responsiveness seen as greater numbers of cells being nonresponsive to visual stimulation, poor tuning of those cells that do respond, and an overall tendency for domination by the contralateral visual input. If the progress of degeneration in one eye is slowed by intraretinal cell transplantation, cortical responses to stimulation of the remaining, untreated, eye are much stronger, better tuned and histograms of ocular dominance resemble more those in normal rats. This suggests that the rescued eye is able to enhance performance in the untreated eye by some form of postsynaptic mechanism.
Plasma membrane localization and function of TRPC1 is dependent on its interaction with β-tubulin in retinal epithelium cells
- SUNITHA BOLLIMUNTHA, ERIC CORNATZER, BRIJ B SINGH
-
- Published online by Cambridge University Press:
- 02 June 2005, pp. 163-170
-
- Article
- Export citation
-
Mammalian homologues of the Drosophila canonical Transient Receptor Potential (TRPC) protein have been proposed to encode the store-operated Ca2+ influx (SOC) channel(s). This study examines the role of TRPC1 in the SOC mechanism of retinal cells. htrpc1 transcript was detected in bovine retinal and in human adult retinal pigment epithelial (ARPE) cells. Western blot analysis also confirmed the expression of TRPC1 protein in neuronal cells including retina and ARPE cells. To determine the role of TRPC1 protein in retinal cells, TRPC1 was recombinantly expressed in ARPE cells and changes in intracellular Ca2+ were analyzed. ARPE cells stably transfected with htrp1 cDNA displayed 2-fold higher Ca2+ influx with no significant increase in the basal influx. Consistent with this the overexpressed TRPC1 protein was localized in the plasma membrane region of ARPE cells. Interestingly, both bovine retinal tissues and ARPE cells showed that TRPC1 protein co-localizes and could be co-immunoprecipitated with β-tubulin. Disruption of tubulin by colchicine significantly decreased both plasma membrane staining of the TRPC1 protein and Ca2+ influx in ARPE cells. These results suggest that TRPC1 channel protein is expressed in retinal cells, further, targeting/retention of the TRPC1 protein to the plasma membrane in retinal cells is mediated via its interaction with β-tubulin.
Toward a unified model of vertebrate rod phototransduction
- R.D. HAMER, S.C. NICHOLAS, D. TRANCHINA, T.D. LAMB, J.L.P. JARVINEN
-
- Published online by Cambridge University Press:
- 06 October 2005, pp. 417-436
-
- Article
- Export citation
-
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.
Chromatin immunoprecipitation identifies photoreceptor transcription factor targets in mouse models of retinal degeneration: New findings and challenges
- GUANG-HUA PENG, SHIMING CHEN
-
- Published online by Cambridge University Press:
- 06 December 2005, pp. 575-586
-
- Article
- Export citation
-
The transcription factors, Otx2, Crx, Nrl, and Nr2e3, expressed by retinal photoreceptor cells are essential for photoreceptor gene expression, development, and maintenance. Malfunction of any of these factors due to genetic mutations causes photoreceptor disease. Protein–protein interaction studies suggest that these factors may form a regulatory network centered on Crx. To understand how these factors regulate photoreceptor gene transcription in vivo, we have employed chromatin immunoprecipitation (ChIP) assays to assess the ability of these proteins to bind to regulatory sequences of photoreceptor genes in the retina of wild-type and mutant mice with photoreceptor degeneration. This paper summarizes the advantages and limitations of ChIP, using examples from our studies to demonstrate how this technique has contributed to our understanding of the regulation of photoreceptor gene expression. We report that Crx, Otx2, Nrl, and Nr2e3 co-occupy the promoter/enhancer, but not the region 3′ of selected Crx target genes, in a retina-specific fashion. We identified Crx-dependent (Nr2e3) and Crx-independent (Otx2 and Nrl) target binding using Crx knockout mice (Crx−/−), suggesting that individual factors may use distinct mechanism(s) for binding and regulating target genes. Consistent with ChIP results, we also found that Otx2, a close family member of Crx, can activate the promoter of rod and cone genes in HEK293 cells, implicating Otx2 in regulating photoreceptor gene expression. These findings provide important information for understanding how photoreceptor transcription factors regulate photoreceptor gene expression and the mechanisms by which mutations in these factors cause transcriptional dysregulation and photoreceptor degeneration.
Rho GTPases regulate rhabdom morphology in octopus photoreceptors
- ARIA M. MILLER, TERESA RAMIREZ, FREDDI I. ZUNIGA, GINA H. OCHOA, SHAUNTE GRAY, SHANNON D. KELLY, BRIAN MATSUMOTO, LAURA J. ROBLES
-
- Published online by Cambridge University Press:
- 02 August 2005, pp. 295-304
-
- Article
- Export citation
-
In the cephalopod retina, light/dark adaptation is accompanied by a decrease/increase in rhabdom size and redistribution of rhodopsin and retinochrome. Rearrangements in the actin cytoskeleton probably govern changes in rhabdom size by regulating the degradation/formation of rhabdomere microvilli. Photopigment movements may be directed by microtubules present in the outer segment core cytoplasm. We believe that rhodopsin activation by light stimulates Rho and Rac signaling pathways, affecting these cytoskeletal systems and their possible functions in controlling rhabdom morphology and protein movements. In this study, we localized cytoskeletal and signaling proteins in octopus photoreceptors to determine their concurrence between the lighting conditions. We used toxin B from Clostridium difficile to inhibit the activity of Rho/Rac and observed its effect on the location of signaling proteins and actin and tubulin. In both lighting conditions, we found Rho in specific sets of juxtaposed rhabdomeres in embryonic and adult retinas. In the light, Rho and actin were localized along the length of the rhabdomere, but, in the dark, both proteins were absent from a space beneath the inner limiting membrane. Rac colocalized with tubulin in the outer segment core cytoplasm and, like Rho, the two proteins were also absent beneath the inner limiting membrane in the dark. The distribution of actin and Rho was affected by toxin B and, in dark-adapted retinas, actin and Rho distribution was similar to that observed in the light. Our results suggest that the Rho/Rac GTPases are candidates for the regulation of rhabdomere size and protein movements in light-dark-adapted octopus photoreceptors.
Effect of temporal sparseness and dichoptic presentation on multifocal visual evoked potentials
- ANDREW C. JAMES, RASA RUSECKAITE, TED MADDESS
-
- Published online by Cambridge University Press:
- 05 April 2005, pp. 45-54
-
- Article
- Export citation
-
Multifocal VEP (mfVEP) responses were obtained from 13 normal human subjects for nine test conditions, covering three viewing conditions (dichoptic and left and right monocular), and three different temporal stimulation forms (rapid contrast reversal, rapid pattern pulse presentation, and slow pattern pulse presentation). The rapid contrast reversal stimulus had pseudorandomized reversals of checkerboards in each visual field region at a mean rate of 25 reversals/s, similar to most mfVEP studies to date. The rapid pattern pulse presentation had pseudorandomized presentations of a checkerboard for one frame, interspersed with uniform grey frames, with a mean rate of 25 presentations/s per region per eye. The slow pattern pulse stimulus had six presentations/s per region per eye. Recording time was 5.3 min/condition. For dichoptic presentation slow pattern pulse responses were 4.6 times larger in amplitude than the contrast reversal responses. Binocular suppression was greatest for the contrast reversal stimulus. Consideration of the signal-to-noise ratios indicated that to achieve a given level of reliability, slow pattern pulse stimuli would require half the recording time of contrast reversal stimuli for monocular viewing, and 0.4 times the recording time for dichoptically presented stimuli. About half the responses to the slow pattern pulse stimuli had peak value exceeding five times their estimated standard error. Responses were about 20% smaller in the upper visual field locations. Space–time decomposition showed that responses to slow pattern pulse were more consistent across visual field locations. We conclude that the pattern pulse stimuli, which we term temporally sparse, maintain the visual system in a high contrast gain state. This more than compensates for the smaller number of presentations in the run, and provides signal-to-noise advantages that may be valuable in clinical application.
Visual evoked potentials for reversals of red–green gratings with different chromatic contrasts: Asymmetries with respect to isoluminance
- INGER RUDVIN
-
- Published online by Cambridge University Press:
- 03 February 2006, pp. 749-758
-
- Article
- Export citation
-
Human visual evoked potentials (VEPs) were recorded for abrupt 6.25-Hz reversals of 2 c/deg square-wave gratings combining red–green contrast with different levels of luminance contrast. Response characteristics— amplitudes and peak latencies as a function of luminance contrast—were compared for four different pairs of red–green colors and an isochromatic yellow grating. For each of the red–green color pairs, the plots of VEP amplitudes and latencies were nonsymmetrical with respect to isoluminance. The amplitude dropped to a minimum within a region of rapid phase change, at a different contrast for each color pair but always at a luminance contrast for which the greener color had the higher luminance. When the contrast-response curve for each of the four red–green pairs was modeled by a simple |CL − CM| opponency of L- and M-cone contrast using a fixed CL/CM weighting ratio of about two, there was a close correspondence between the contrast giving a null in the modeled response and that giving a minimum in the VEP amplitude. So for the stimulus parameters applied here, the reversal VEP appeared to be dominated by L/M-opponent response contributions for which the signed CL/CM-cone weighting ratio was close to a value of minus two rather than to a value of minus one, which is characteristic of the psychophysical red–green detection mechanism and representative of CL/CM weighting ratios for precortical cells in the parvocellular pathway.
Reciprocal inhibition of voltage-gated potassium currents (IK(V)) by activation of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish retina
- SHIH-FANG FAN, STEPHEN YAZULLA
-
- Published online by Cambridge University Press:
- 05 April 2005, pp. 55-63
-
- Article
- Export citation
-
Cannabinoid CB1 receptor (via Gs) and dopamine D2 receptor (via Gi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1 and D1 receptors, but not D2 receptors, we focused on whether CB1 receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+ currents IK(V) of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents were recorded from Mb bipolar cells in goldfish retinal slices. Mb bipolar cells were identified by intracellular filling with Lucifer yellow. The bath solution was calcium-free and contained 1 mM cobalt to block indirect calcium-dependent effects. Dopamine (10 μM) consistently increased IK(V) by a factor of 1.57 ± 0.12 (S.E.M., n = 15). A CB receptor agonist, WIN 55212-2 (0.25–1 μM), had no effect, but 4 μM WIN 55212-2 suppressed IK(V) by 60%. If IK(V) was first increased by 10 μM dopamine, application of WIN 55212-2 (0.25–1 μM) reversibly blocked the effect of dopamine even though these concentrations of WIN 55212-2 had no effect of their own. If WIN 55212-2 was applied first and dopamine (10 μM) was added to the WIN-containing solution, 0.1 μM WIN 55212-2 blocked the effect of dopamine. All effects of WIN 55212-2 were blocked by coapplication of SR 141716A (CB1 antagonist) and pretreatment with pertussis toxin (blocker of Gi/o) indicating action via CB1 receptor activation of G protein Gi/o. Coactivation of CB1 and D1 receptors on Mb bipolar cells produces reciprocal effects on IK(V). The CB1-evoked suppression of IK(V) is mediated by G protein Gi/o, whereas the D1-evoked enhancement is mediated by G protein Gs. As dopamine is a retinal “light” signal, these data support our notion that endocannabinoids function as a “dark” signal, interacting with dopamine to set retinal sensitivity.
Development of the primate area of high acuity, 3: Temporal relationships between pit formation, retinal elongation and cone packing
- A.D. SPRINGER, A.E. HENDRICKSON
-
- Published online by Cambridge University Press:
- 02 June 2005, pp. 171-185
-
- Article
- Export citation
-
By establishing an avascular, highly elastic, region within the fetal area of high acuity (AHA), the developing primate eye has created a unique substrate on which the mechanical forces of intraocular pressure (IOP) and growth-induced retinal stretch (stretch) can act. We proposed (Springer & Hendrickson, 2004b) that these forces generate both the pit and high cone density found in the adult AHA. In this paper, we use quantitative measures to determine the temporal relationships between nasal and temporal retinal elongation, changes in pit depth, cone packing, and cone morphology over M. nemestrina retinal development. Retinal length increased rapidly to about 105 days postconception (dpc; Phase 1) and then elongation virtually ceased (Phase 2) until just after birth (180 dpc). Retinal elongation due to stretch resumed during Phase 3 until approximately 315 dpc (4–5 months), after which time the retina appeared mature (Phase 4). The pit appeared during the quiescent Phase 2, suggesting that IOP acts, in conjunction with molecular changes in the inner retina, on the highly elastic, avascular, AHA to generate a deep, narrow pit and causes inner retinal cellular displacements. Subsequently (Phase 3), the pit widened, became 50% shallower and central inner retinal lamina thinned slightly due to a small amount of retinal stretch occurring in the AHA. Centripetal movement of cones was minimal until just after birth when the pit reached 88% of its maximal depth. Accelerated cone packing during Phase 3 was temporally correlated with increased stretch. A slight stretching of the central inner retina generates “lift” forces that cause the pit to become shallower and wider. In turn, these “lift” forces draw cones toward the center of the AHA (Springer, 1999). Localized changes in cone morphology associated with packing, included smaller cell body size, a change from a monolayer to a multilayered mound of cell bodies, elongation of inner segments and tilting of the apical portion toward the AHA. These changes began in cones overlying the edges of the pit, not its center. Henle cone axons formed initially in association with centrifugal displacement of the inner retina during pit formation, with an additional subsequent elongation due to cones moving centripetally. An integrated, two-factor model of AHA formation is presented. Initially, during the second half of gestation (Phase 2), IOP acts on the hyperelastic avascular zone of the AHA to generate a deep pit in the inner retina. In the first 4 months after birth (Phase 3), central retinal stretch generates tensile “lift” forces that remodel the pit and pack cones by drawing them toward the AHA center.
Mouse models of ocular diseases
- B. CHANG, N.L. HAWES, R.E. HURD, J. WANG, D. HOWELL, M.T. DAVISSON, T.H. RODERICK, S. NUSINOWITZ, J.R. HECKENLIVELY
-
- Published online by Cambridge University Press:
- 06 December 2005, pp. 587-593
-
- Article
- Export citation
-
The Jackson Laboratory, having the world's largest collection of mouse mutant stocks and genetically diverse inbred strains, is an ideal place to discover genetically determined eye variations and disorders. In this paper, we list and describe mouse models for ocular research available from Mouse Eye Mutant Resource at The Jackson Laboratory. While screening mouse strains and stocks at The Jackson Laboratory (TJL) for genetic mouse models of human ocular disorders, we have identified numerous spontaneous or naturally occurring mutants. We characterized these mutants using serial indirect ophthalmoscopy, fundus photography, electroretinography (ERG) and histology, and performed genetic analysis including linkage studies and gene identification. Utilizing ophthalmoscopy, electroretinography, and histology, to date we have discovered 109 new disorders affecting all aspects of the eye including the lid, cornea, iris, lens, and retina, resulting in corneal disorders, glaucoma, cataracts, and retinal degenerations. The number of known serious or disabling eye diseases in humans is large and affects millions of people each year. Yet research on these diseases frequently is limited by the obvious restrictions on studying pathophysiologic processes in the human eye. Likewise, many human ocular diseases are genetic in origin, but appropriate families often are not readily available for genetic studies. Mouse models of inherited ocular disease provide powerful tools for rapid genetic analysis, characterization, and gene identification. Because of the great similarity among mammalian genomes, these findings in mice have direct relevance to the homologous human conditions.
Glycine- and GABA-activated inhibitory currents on axon terminals of rabbit cone bipolar cells
- CHENGWEN ZHOU, RAMON F. DACHEUX
-
- Published online by Cambridge University Press:
- 03 February 2006, pp. 759-767
-
- Article
- Export citation
-
Glycine- and GABA-activated currents were examined in the axon terminals of 12 types of rabbit cone bipolar cells. In the superfused retinal slice, a cell was voltage clamped at 0 mV in the presence of cobalt; then glycine or GABA was puffed onto the axon terminal. Types CBa1, CBa2, and a few CBa1-2 cells demonstrated larger glycine-activated currents than GABA-activated ones. However, some OFF cells (CBa2n, CBa1-2n, CBa1w), most CBa1-2, and most ON cells (CBb3, CBb3-4, CBb3n, and CBb4) displayed larger GABA-activated currents. The ON cell, CBb5, possessed only a GABA-activated current. The predominance of glycinergic currents in CBa1, CBa2, and a few CBa1-2 cells suggests a major input from the glycinergic AII amacrine cell and thus a key role for these cells in the rod bipolar pathway. Certain OFF cells (most CBa1-2) expressed larger GABA-activated currents. All types expressed both GABAA and GABAC currents about equally, although most OFF types (CBa1, CB a2n, CBa1-2, and CBa2n) displayed a slightly greater GABAA component.
Response of the difference-of-Gaussians model to circular drifting-grating patches
- G.T. EINEVOLL, H.E. PLESSER
-
- Published online by Cambridge University Press:
- 06 October 2005, pp. 437-446
-
- Article
- Export citation
-
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.
Connections of contralaterally projecting isthmotectal axons and GABA-immunoreactive neurons in Xenopus tectum: An ultrastructural study
- KRYSTYNA KIELAN RYBICKA, SUSAN B. UDIN
-
- Published online by Cambridge University Press:
- 02 August 2005, pp. 305-315
-
- Article
- Export citation
-
To investigate the circuitry that mediates binocular interactions in the tectum of Xenopus frogs, we have begun to identify the tectal cells that receive ipsilateral eye input relayed via the nucleus isthmi. Isthmotectal axons were labeled with horseradish peroxidase, and thin sections were labeled by postembedding immunogold reaction with antibodies to γ-aminobutyric acid (GABA). Ultrastructural examination reveals that many isthmotectal axons terminate on GABA-immunoreactive dendrites. Other isthmotectal axons contact postsynaptic structures that are unlabeled but have an appearance consistent with previously described GABA-poor zones of GABA-immunoreactive dendrites. We also examined the unlabeled inputs to the dendrites that were postsynaptic to filled isthmotectal axons. The most common nonisthmic inputs to those dendrites were GABA-immunoreactive processes with symmetric morphology. Surprisingly, we found only one input with the retinotectal characteristics of densely packed round, clear vesicles and minimal GABA immunoreactivity. These results indicate that isthmotectal axons synapse onto inhibitory interneurons, that retinotectal and isthmotectal axons do not synapse close to each other on the same dendrites, and that inhibitory connections are the closest neighbors to isthmotectal synapses.
Stimulus-dependent correlated firing in directionally selective retinal ganglion cells
- FRANKLIN R. AMTHOR, JOHN S. TOOTLE, NORBERTO M. GRZYWACZ
-
- Published online by Cambridge University Press:
- 03 February 2006, pp. 769-787
-
- Article
- Export citation
-
Synchronous spiking has been postulated to be a meta-signal in visual cortex and other CNS loci that tags neuronal spike responses to a single entity. In retina, however, synchronized spikes have been postulated to arise via mechanisms that would largely preclude their carrying such a code. One such mechanism is gap junction coupling, in which synchronous spikes would be a by-product of lateral signal sharing. Synchronous spikes have also been postulated to arise from common-source inputs to retinal ganglion cells having overlapping receptive fields, and thus code for stimulus location in the overlap area. On–Off directionally selective ganglion cells of the rabbit retina exhibit a highly precise tiling pattern in which gap junction coupling occurs between some neighboring, same-preferred-direction cells. Depending on how correlated spikes arise, and for what purpose, one could postulate that synchronized spikes in this system (1) always arise in some subset of same-direction cells because of gap junctions, but never in non-same-preferred-directional cells; (2) never arise in same-directional cells because their receptive fields do not overlap, but arise only in different-directional cells whose receptive fields overlap, as a code for location in the overlap region; or (3) arise in a stimulus-dependent manner for both same- and different-preferred-direction cells for a function similar to that postulated for neurons in visual cortex. Simultaneous, extracellular recordings were obtained from neighboring On–Off directionally selective (DS) ganglion cells having the same and different preferred directions in an isolated rabbit retinal preparation. Stimulation by large flashing spots elicited responses from DS ganglion-cell pairs that typically showed little synchronous firing. Movement of extended bars, however, often produced synchronous spikes in cells having similar or orthogonal preferred directions. Surprisingly, correlated firing could occur for the opposite contrast polarity edges of moving stimuli when the leading edge of a sweeping bar excited the receptive field of one cell as its trailing edge stimulated another. Pharmacological manipulations showed that the spike synchronization is enhanced by excitatory cholinergic amacrine-cell inputs, and reduced by inhibitory GABAergic inputs, in a motion-specific manner. One possible interpretation is that this synchronous firing could be a signal to higher centers that the outputs of the two DS ganglion cells should be “bound” together as responding to a contour of a common object.
Simulation analysis of receptive-field size of retinal horizontal cells by ionic current model
- TOSHIHIRO AOYAMA, YOSHIMI KAMIYAMA, SHIRO USUI
-
- Published online by Cambridge University Press:
- 05 April 2005, pp. 65-78
-
- Article
- Export citation
-
The size of the receptive field of retinal horizontal cells changes with the state of dark/light adaptation. We have used a mathematical model to determine how changes in the membrane conductance affect the receptive-field properties of horizontal cells. We first modeled the nonlinear membrane properties of horizontal cells based on ionic current mechanisms. The dissociated horizontal cell model reproduced the voltage–current (V–I) relationships for various extracellular glutamate concentrations measured in electrophysiological studies. Second, a network horizontal cell model was also described, and it reproduced the V–I relationship observed in vivo. The network model showed a bell-shaped relationship between the receptive-field size and constant glutamate concentration. The simulated results suggest that the calcium current is a candidate for the bell-shaped length constant relationship.
Functional and cortical adaptations to central vision loss
- SING-HANG CHEUNG, GORDON E. LEGGE
-
- Published online by Cambridge University Press:
- 02 June 2005, pp. 187-201
-
- Article
- Export citation
-
Age-related macular degeneration (AMD), affecting the retina, afflicts one out of ten people aged 80 years or older in the United States. AMD often results in vision loss to the central 15–20 deg of the visual field (i.e. central scotoma), and frequently afflicts both eyes. In most cases, when the central scotoma includes the fovea, patients will adopt an eccentric preferred retinal locus (PRL) for fixation. The onset of a central scotoma results in the absence of retinal inputs to corresponding regions of retinotopically mapped visual cortex. Animal studies have shown evidence for reorganization in adult mammals for such cortical areas following experimentally induced central scotomata. However, it is still unknown whether reorganization occurs in primary visual cortex (V1) of AMD patients. Nor is it known whether the adoption of a PRL corresponds to changes to the retinotopic mapping of V1. Two recent advances hold out the promise for addressing these issues and for contributing to the rehabilitation of AMD patients: improved methods for assessing visual function across the fields of AMD patients using the scanning laser ophthalmoscope, and the advent of brain-imaging methods for studying retinotopic mapping in humans. For the most part, specialists in these two areas come from different disciplines and communities, with few opportunities to interact. The purpose of this review is to summarize key findings on both the clinical and neuroscience issues related to questions about visual adaptation in AMD patients.
The Tennessee Mouse Genome Consortium: Identification of ocular mutants
- MONICA M. JABLONSKI, XIAOFEI WANG, LU LU, DARLA R. MILLER, EUGENE M. RINCHIK, ROBERT W. WILLIAMS, DANIEL GOLDOWITZ
-
- Published online by Cambridge University Press:
- 06 December 2005, pp. 595-604
-
- Article
- Export citation
-
The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases and disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.