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1
Reinhard, Katja, and Thomas A. Münch. "Visual properties of human retinal ganglion cells." PLOS ONE 16, no. 2 (February 16, 2021): e0246952. http://dx.doi.org/10.1371/journal.pone.0246952.
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The retinal output is the sole source of visual information for the brain. Studies in non-primate mammals estimate that this information is carried by several dozens of retinal ganglion cell types, each informing the brain about different aspects of a visual scene. Even though morphological studies of primate retina suggest a similar diversity of ganglion cell types, research has focused on the function of only a few cell types. In human retina, recordings from individual cells are anecdotal or focus on a small subset of identified types. Here, we present the first systematic ex-vivo recording of light responses from 342 ganglion cells in human retinas obtained from donors. We find a great variety in the human retinal output in terms of preferences for positive or negative contrast, spatio-temporal frequency encoding, contrast sensitivity, and speed tuning. Some human ganglion cells showed similar response behavior as known cell types in other primate retinas, while we also recorded light responses that have not been described previously. This first extensive description of the human retinal output should facilitate interpretation of primate data and comparison to other mammalian species, and it lays the basis for the use of ex-vivo human retina for in-vitro analysis of novel treatment approaches.
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Kanamoto, Takashi, Yasushi Kitaoka, Hiroaki Sakaue, Yusuke Murakami, Yasuhiro Ikeda, Kei Tobiume, and Yoshiaki Kiuchi. "D-Serine Induced by Ocular Hypertension is Associated with Retinal Cell Death." Current Trends in Ophthalmology 1, no. 1 (July 3, 2018): 23–29. http://dx.doi.org/10.18314/ctoy.v1i1.1161.
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Purpose: The purpose of this study is to investigate the role of free D-serine in the death of retinal cells caused by ocular hypertension.Methods: Adult Wistar rats were used as an experimental model of ocular hypertension. Immunohistochemistry was used to identify the retinal sites and expression patterns of D-serine and serine racemase in the rat retina. The concentrations of free D-serine and L-serine in the retina were measured by two-dimensional high-performance liquid chromatography. Retinal cell death was investigated by Immunohistochemistry.Results: D-serine was expressed on the retinal ganglion cell layer in the retinas of rats with ocular hypertension. A serine racemase was specifically expressed in the retinal ganglion cells. The ratio of free D-/L-serine in the retinas with ocular hypertension was higher than that in the retinas with normal tension. Annexing-V-positive cells were observed in the retinal ganglion cell layer in the retinas of the rats with ocular hypertension, and these cells were also co-localized with D-serine expression.Conclusions: We suspect that the up-regulation of serine racemase expression induced by ocular hypertensionleads to an increase in free D-serine converted from free L-serine in retinal ganglion cells and that retinal cell death is associated with D-serine expression.
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Wang, Steven W., Xiuqian Mu, William J. Bowers, Dong-Seob Kim, Daniel J. Plas, Michael C. Crair, Howard J. Federoff, Lin Gan, and William H. Klein. "Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth." Development 129, no. 2 (January 15, 2002): 467–77. http://dx.doi.org/10.1242/dev.129.2.467.
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In mice, Brn3 POU domain transcription factors play essential roles in the differentiation and survival of projection neurons within the retina, inner ear, dorsal root and trigeminal ganglia. During retinal ganglion cell differentiation, Brn3b is expressed first, followed by Brn3a and Brn3c. Targeted deletion of Brn3b, but not Brn3a or Brn3c, leads to a loss of most retinal ganglion cells before birth. However, as a few retinal ganglion cells are still present in Brn3b–/– mice, Brn3a and Brn3c may partially compensate for the loss of Brn3b. To examine the role of Brn3c in retinal ganglion cell development, we generated Brn3b/Brn3c double knockout mice and analyzed their retinas and optic chiasms. Retinal ganglion cell axons from double knockout mice were more severely affected than were those from Brn3b-deficient mice, indicating that Brn3c was required for retinal ganglion cell differentiation and could partially compensate for the loss of Brn3b. Moreover, Brn3c had functions in retinal ganglion cell differentiation separate from those of Brn3b. Ipsilateral and misrouted projections at the optic chiasm were overproduced in Brn3b–/– mice but missing were entirely in optic chiasms of Brn3b/Brn3c double knockout mice, suggesting that Brn3c controlled ipsilateral axon production. Forced expression of Brn3c in Brn3b–/– retinal explants restored neurite outgrowth, demonstrating that Brn3c could promote axon outgrowth in the absence of Brn3b. Our results reveal a complex genetic relationship between Brn3b and Brn3c in regulating the retinal ganglion cell axon outgrowth.
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Waid, D. K., and S. C. McLoon. "Ganglion cells influence the fate of dividing retinal cells in culture." Development 125, no. 6 (March 15, 1998): 1059–66. http://dx.doi.org/10.1242/dev.125.6.1059.
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The different retinal cell types arise during vertebrate development from a common pool of progenitor cells. The mechanisms responsible for determining the fate of individual retinal cells are, as yet, poorly understood. Ganglion cells are one of the first cell types to be produced in the developing vertebrate retina and few ganglion cells are produced late in development. It is possible that, as the retina matures, the cellular environment changes such that it is not conducive to ganglion cell determination. The present study showed that older retinal cells secrete a factor that inhibits the production of ganglion cells. This was shown by culturing younger retinal cells, the test population, adjacent to various ages of older retinal cells. Increasingly older retinal cells, up to embryonic day 9, were more effective at inhibiting production of ganglion cells in the test cell population. Ganglion cell production was restored when ganglion cells were depleted from the older cell population. This suggests that ganglion cells secrete a factor that actively prevents cells from choosing the ganglion cell fate. This factor appeared to be active in medium conditioned by older retinal cells. Analysis of the conditioned medium established that the factor was heat stable and was present in the <3 kDa and >10 kDa fractions. Previous work showed that the neurogenic protein, Notch, might also be active in blocking production of ganglion cells. The present study showed that decreasing Notch expression with an antisense oligonucleotide increased the number of ganglion cells produced in a population of young retinal cells. Ganglion cell production, however, was still inhibited in cultures using antisense oligonucleotide to Notch in medium conditioned by older retinal cells. This suggests that the factor secreted by older retinal cells inhibits ganglion cell production through a different pathway than that mediated by Notch.
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Silveira, L. C. L., C. W. Picanço-Diniz, and E. Oswaldo-Cruz. "Distribution and size of ganglion cells in the retinae of large Amazon rodents." Visual Neuroscience 2, no. 3 (March 1989): 221–35. http://dx.doi.org/10.1017/s0952523800001140.
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AbstractThe topographical distribution of density and soma size of the retinal ganglion cells were studied in three species of hystricomorph rodents. Flat-mounted retinae were stained by the Nissl method and the ganglion cells counted on a matrix covering the whole retinae. Soma size was determined for samples at different retinal regions. The agouti, a diurnal rodent, shows a well-developed visual streak, reaching a peak density of 6250 ganglion cells/mm2. The total number of ganglion cells ranged from 477, 427–548, 205 in eight retinae. The ganglion-cell-size histogram of the visual streak region exhibits a marked shift towards smaller values when compared to retinal periphery. Upper and lower regions differ in both cell density and cell size. The crepuscular capybara shows a less-developed visual streak with a peak ganglion cell density of 2250/mm2. The shift towards small-sized cells in the visual streak is less marked. Total ganglion cell population is 368,840. In the nocturnal paca, the upper half of the fundus oculi includes a tapetum lucidum. The retina of this species shows the least-developed visual streak of this group, with the lowest peak ganglion cell density reaching 925/mm2. The total ganglion cell number (230,804) is also smaller than in the two other species. Soma-size spectra of this species are characterized by the presence, in the lower hemi-retina, of very large perikarya comparable in size to the cat's alpha ganglion cells.
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Sekirnjak, Chris, Clare Hulse, Lauren H. Jepson, Pawel Hottowy, Alexander Sher, Wladyslaw Dabrowski, A. M. Litke, and E. J. Chichilnisky. "Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration." Journal of Neurophysiology 102, no. 6 (December 2009): 3260–69. http://dx.doi.org/10.1152/jn.00663.2009.
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Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of ∼10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60–70% at all ages. Surprisingly, thresholds (∼0.05 mC/cm2) and latencies (∼0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.
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Troilo, David, Meijuan Xiong, Justin C. Crowley, and Barbara L. Finlay. "Factors controlling the dendritic arborization of retinal ganglion cells." Visual Neuroscience 13, no. 4 (July 1996): 721–33. http://dx.doi.org/10.1017/s0952523800008609.
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AbstractThe effects of changing retinal ganglion cell (RGC) density and availability of presynaptic sites on the development of RGC dendritic arbor in the developing chick retina were contrasted. Visual form deprivation was used to induce ocular enlargement and expanded retinal area resulting in a 20–30% decrease in RGC density. In these retinas, RGC dendritic arbors increased in a compensatory manner to maintain the inner nuclear layer to RGC convergence ratio in a way that is consistent with simple stretching; RGC dendritic arbors become larger with increased branch lengths, but without change in the total number of branches. In the second manipulation, partial optic nerve section was used to produce areas of RGC depletion of approximately 60% in the central retina. This reduction in density is comparable to the density of locations in the normal peripheral retina. In RGC-depleted retinas, dendritic arbor areas of RGCs in the central retina grow to match the size of normal peripheral arbors. In contrast to the expanded case, two measures of intrinsic arbor structure are changed in RGC-depleted retinas; the branch density of RGC dendrites is greater, and the relative areas of the two arbors of bistratified cells are altered. We discuss the potential roles of retinal growth, local RGC density, and availability of presynaptic terminals in the developmental control of RGC dendritic arbor.
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Grosberg, Lauren E., Karthik Ganesan, Georges A. Goetz, Sasidhar S. Madugula, Nandita Bhaskhar, Victoria Fan, Peter Li, et al. "Activation of ganglion cells and axon bundles using epiretinal electrical stimulation." Journal of Neurophysiology 118, no. 3 (September 1, 2017): 1457–71. http://dx.doi.org/10.1152/jn.00750.2016.
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Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.
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Greco, Jordan A., Nicole L. Wagner, Ralph J. Jensen, Daniel B. Lawrence, Matthew J. Ranaghan, Megan N. Sandberg, Daniel J. Sandberg, and Robert R. Birge. "Activation of retinal ganglion cells using a biomimetic artificial retina." Journal of Neural Engineering 18, no. 6 (December 1, 2021): 066027. http://dx.doi.org/10.1088/1741-2552/ac395c.
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Abstract Objective. Biomimetic protein-based artificial retinas offer a new paradigm for restoring vision for patients blinded by retinal degeneration. Artificial retinas, comprised of an ion-permeable membrane and alternating layers of bacteriorhodopsin (BR) and a polycation binder, are assembled using layer-by-layer electrostatic adsorption. Upon light absorption, the oriented BR layers generate a unidirectional proton gradient. The main objective of this investigation is to demonstrate the ability of the ion-mediated subretinal artificial retina to activate retinal ganglion cells (RGCs) of degenerated retinal tissue. Approach. Ex vivo extracellular recording experiments with P23H line 1 rats are used to measure the response of RGCs following selective stimulation of our artificial retina using a pulsed light source. Single-unit recording is used to evaluate the efficiency and latency of activation, while a multielectrode array (MEA) is used to assess the spatial sensitivity of the artificial retina films. Main results. The activation efficiency of the artificial retina increases with increased incident light intensity and demonstrates an activation latency of ∼150 ms. The results suggest that the implant is most efficient with 200 BR layers and can stimulate the retina using light intensities comparable to indoor ambient light. Results from using an MEA show that activation is limited to the targeted receptive field. Significance. The results of this study establish potential effectiveness of using an ion-mediated artificial retina to restore vision for those with degenerative retinal diseases, including retinitis pigmentosa.
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Vlasiuk, Anastasiia, and Hiroki Asari. "Feedback from retinal ganglion cells to the inner retina." PLOS ONE 16, no. 7 (July 22, 2021): e0254611. http://dx.doi.org/10.1371/journal.pone.0254611.
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Retinal ganglion cells (RGCs) are thought to be strictly postsynaptic within the retina. They carry visual signals from the eye to the brain, but do not make chemical synapses onto other retinal neurons. Nevertheless, they form gap junctions with other RGCs and amacrine cells, providing possibilities for RGC signals to feed back into the inner retina. Here we identified such feedback circuitry in the salamander and mouse retinas. First, using biologically inspired circuit models, we found mutual inhibition among RGCs of the same type. We then experimentally determined that this effect is mediated by gap junctions with amacrine cells. Finally, we found that this negative feedback lowers RGC visual response gain without affecting feature selectivity. The principal neurons of the retina therefore participate in a recurrent circuit much as those in other brain areas, not being a mere collector of retinal signals, but are actively involved in visual computations.
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Kuhrt, Heidrun, Andreas Bringmann, Wolfgang Härtig, Gudrun Wibbelt, Leo Peichl, and Andreas Reichenbach. "The Retina of Asian and African Elephants: Comparison of Newborn and Adult." Brain, Behavior and Evolution 89, no. 2 (2017): 84–103. http://dx.doi.org/10.1159/000464097.
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Elephants are precocial mammals that are relatively mature as newborns and mobile shortly after birth. To determine whether the retina of newborn elephants is capable of supporting the mobility of elephant calves, we compared the retinal structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of both species by immunohistochemical and morphometric methods. For the first time, we present here a comprehensive qualitative and quantitative characterization of the cellular composition of the newborn and the adult retinas of 2 elephant species. We found that the retina of elephants is relatively mature at birth. All retinal layers were well discernible, and various retinal cell types were detected in the newborns, including Müller glial cells (expressing glutamine synthetase and cellular retinal binding protein; CRALBP), cone photoreceptors (expressing S-opsin or M/L-opsin), protein kinase Cα-expressing bipolar cells, tyrosine hydroxylase-, choline acetyltransferase (ChAT)-, calbindin-, and calretinin-expressing amacrine cells, and calbindin-expressing horizontal cells. The retina of newborn elephants contains discrete horizontal cells which coexpress ChAT, calbindin, and calretinin. While the overall structure of the retina is very similar between newborn and adult elephants, various parameters change after birth. The postnatal thickening of the retinal ganglion cell axons and the increase in ganglion cell soma size are explained by the increase in body size after birth, and the decreases in the densities of neuronal and glial cells are explained by the postnatal expansion of the retinal surface area. The expression of glutamine synthetase and CRALBP in the Müller cells of newborn elephants suggests that the cells are already capable of supporting the activities of photoreceptors and neurons. As a peculiarity, the elephant retina contains both normally located and displaced giant ganglion cells, with single cells reaching a diameter of more than 50 µm in adults and therefore being almost in the range of giant retinal ganglion cells found in aquatic mammals. Some of these ganglion cells are displaced into the inner nuclear layer, a unique feature of terrestrial mammals. For the first time, we describe here the occurrence of many bistratified rod bipolar cells in the elephant retina. These bistratified bipolar cells may improve nocturnal contrast perception in elephants given their arrhythmic lifestyle.
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OI, HANAKO, GLORIA J. PARTIDA, SHERWIN C. LEE, and ANDREW T. ISHIDA. "HCN4-like immunoreactivity in rat retinal ganglion cells." Visual Neuroscience 25, no. 1 (January 2008): 95–102. http://dx.doi.org/10.1017/s095252380808005x.
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Antisera directed against hyperpolarization-activated, cyclic nucleotide–sensitive (HCN) channels bind to somata in the ganglion cell layer of rat and rabbit retinas, and mRNA for different HCN channel isoforms has been detected in the ganglion cell layer of mouse retina. However, previous studies neither provided evidence that any of the somata are ganglion cells (as opposed to displaced amacrine cells) nor quantified these cells. We therefore tested whether isoform-specific anti-HCN channel antisera bind to ganglion cells labeled by retrograde transport of fluorophore-coupled dextran. In flat-mounted adult rat retinas, the number of dextran-backfilled ganglion cells agreed with cell densities reported in previous studies, and anti-HCN4 antisera bound to the somata of approximately 40% of these cells. The diameter of these somata ranged from 7 to 30 μm. Consistent with localization to cell membranes, the immunoreactivity formed a thin line that circumscribed individual somata. Optic fiber layer axon fascicles, and the proximal dendrites of some ganglion cells, also displayed binding of anti-HCN4 antisera. These results suggest that the response of some mammalian retinal ganglion cells to hyperpolarization may be modulated by changes in intracellular cAMP levels, and could thus be more complex than expected from previous voltage and current recordings.
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GRÜNERT, ULRIKE, and KRISHNA K. GHOSH. "Midget and parasol ganglion cells of the primate retina express the α1 subunit of the glycine receptor." Visual Neuroscience 16, no. 5 (September 1999): 957–66. http://dx.doi.org/10.1017/s0952523899165155.
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Glycine is a major inhibitory neurotransmitter in the mammalian retina and has been shown to influence the responses of ganglion cells. Midget and parasol ganglion cells serve distinct physiological roles in the primate retina and show differences in their response characteristics to light stimuli. In the present study, we addressed the question of whether the expression of glycine receptors differs in midget and parasol ganglion cells. Ganglion cells in the retinae of marmoset and macaque monkeys were injected with Neurobiotin in a live in vitro retinal whole-mount preparation. Retinal pieces were then processed with an antibody against the α1 subunit of the glycine receptor. Strong punctate immunoreactivity indicative of synaptic localization is present in the ON and OFF sublamina of the inner plexiform layer. Many of the immunoreactive puncta coincide with the dendrites of both midget and parasol ganglion cells. Immunoreactive puncta are present on distal and proximal dendrites of ON and OFF cells. These results suggest that ON and OFF midget and parasol cells do not differ with respect to the distribution of the α1 subunit of the glycine receptor.
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YOSHIKAWA, MASAYASU, KAJ ANDERSON, HIRONOBU SAKAGUCHI, JOHN G. FLANNERY, PAUL G. FITZGERALD, and ANDREW T. ISHIDA. "Voltage-gated Na+ channel EOIII-segment-like immunoreactivity in fish retinal ganglion cells." Visual Neuroscience 17, no. 4 (July 2000): 647–55. http://dx.doi.org/10.1017/s0952523800174139.
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Although single-channel and whole-cell patch-clamp recordings have demonstrated the presence of Na+ currents in retinal ganglion cell somata, it has not previously been reported that an anti-Na+-channel antiserum stains both retinal ganglion cell somata and proteins with molecular weights corresponding to complexes of α and β subunits. We probed adult goldfish retinas for Na+ channel-like immunoreactivity with a polyclonal antibody directed against the EOIII segment of vertebrate voltage-gated Na+ channels. In vertical sections and whole mounts, this antibody consistently stained the somata, axons, and proximal dendrites of retinal ganglion cells. Some somata in the proximal third of the inner nuclear layer were also stained. In Western blots, this antibody specifically stained multiple protein bands from retina and optic nerve, all with apparent molecular weights between 200 and 315 kDa. The largest of these molecular weights agrees with that reported previously for complexes of α and β subunits in mammalian neurons, including retinal ganglion cells. The intermediate and lowest molecular weights are consistent with the presence of multiple Na+ channel α subunits, either in individual proximal retinal neurons or in different morphological subtypes.
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Fitzgibbon, T., R. J. Wingate, and I. D. Thompson. "Soma and axon diameter distributions and central projections of ferret retinal ganglion cells." Visual Neuroscience 13, no. 4 (July 1996): 773–86. http://dx.doi.org/10.1017/s0952523800008646.
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AbstractUsing a combination of retrograde horseradish peroxidase (HRP) labelling, silver staining, and electron microscopy, we have assessed the relationship between retinal ganglion cell soma size and axon diameter in the adult ferret (Mustela putorius furo). Retinal ganglion cells were labelled following injections of HRP into the lateral geniculate nucleus (LGN), superior colliculus (SC), or LGN+SC. The soma size distributions following LGN, SC, or LGN+SC injections were all unimodal showing considerable overlap between different cell classes. This was confirmed for alpha cells, identified on the basis of dendritic filling or from neurofibrillar-stained retinae. Analysis of the soma size and axon diameters of a population of heavily labelled retinal ganglion cells showed a significant correlation between the two. However, the overall distribution of intraretinal axon diameter was bimodal with an extended tail. Analysis of the ganglion cell distributions in the adult ferret indicates that beta cells comprise about 50.5–55%, gamma 42.5–47%, and alpha 2.5% of the ganglion cell population. This implies that the proportion of gamma, beta, alpha cells in both cat and ferret retina is highly conserved despite differences in visual specialization in the two species.
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Uzzell, V. J., and E. J. Chichilnisky. "Precision of Spike Trains in Primate Retinal Ganglion Cells." Journal of Neurophysiology 92, no. 2 (August 2004): 780–89. http://dx.doi.org/10.1152/jn.01171.2003.
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Recent studies have revealed striking precision in the spike trains of retinal ganglion cells in several species and suggested that this precision could be an important aspect of visual signaling. However, the precision of spike trains has not yet been described in primate retina. The spike time and count variability of parasol (magnocellular-projecting) retinal ganglion cells was examined in isolated macaque monkey retinas stimulated with repeated presentations of high contrast, spatially uniform intensity modulation. At the onset of clearly delineated periods of firing, retinal ganglion cells fired spikes time-locked to the stimulus with a variability across trials as low as 1 ms. Spike count variance across trials was much lower than the mean and sometimes approached the minimum variance possible with discrete counts, inconsistent with Poisson statistics expected from independently generated spikes. Spike time and count variability decreased systematically with stimulus strength. These findings were consistent with a model in which firing probability was determined by a stimulus-driven free firing rate modulated by a recovery function representing the action potential absolute and relative refractory period.
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Sarthy, P. V., and M. Fu. "Localization of laminin B1 mRNA in retinal ganglion cells by in situ hybridization." Journal of Cell Biology 110, no. 6 (June 1, 1990): 2099–108. http://dx.doi.org/10.1083/jcb.110.6.2099.
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In the nervous system, neuronal migration and axonal growth are dependent on specific interactions with extracellular matrix proteins. During development of the vertebrate retina, ganglion cell axons extend along the internal limiting (basement) membrane and form the optic nerve. Laminin, a major component of basement membranes, is known to be present in the internal limiting membrane, and might be involved in the growth of ganglion cell axons. The identity of the cells that produce retinal laminin, however, has not been established. In the present study, we have used in situ hybridization to localize the sites of laminin B1 mRNA synthesis in the developing mouse retina. Our results show that there are at least two principal sites of laminin B1 mRNA synthesis: (a) the hyaloid vessels and the lens during the period of major axonal outgrowth, and (b) the retinal ganglion cells at later development stages. Müller (glial) cells, the major class of nonneuronal cells in the retina, do not appear to express laminin B1 mRNA either during development or in the adult retina. In Northern blots, we found a single transcript of approximately 6-kb size that encodes the laminin B1 chain in the retina. Moreover, laminin B1 mRNA level was four- to fivefold higher in the postnatal retina compared to that in the adult. Our results show that in addition to nonneuronal cells, retinal ganglion cells also synthesize laminin. The function of laminin in postnatal retinas, however, remains to be elucidated. Nevertheless, our findings raise the possibility that neurons in other parts of the nervous system might also synthesize extracellular matrix proteins.
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Deich, C., B. Seifert, L. Peichl, and A. Reichenbach. "Development of dendritic trees of rabbit retinal alpha ganglion cells: Relation to differential retinal growth." Visual Neuroscience 11, no. 5 (September 1994): 979–88. http://dx.doi.org/10.1017/s0952523800003916.
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AbstractTo provide a quantitative description of the postnatal development of dendritic trees in alpha ganglion cells of the rabbit retina, these cells were stained either by intracellular injection of Lucifer yellow or by application of the lipophilic dye Oil. This was done at three developmental stages: postnatal day (P) 8/9, P 16/17, and in adults. For different retinal locations we quantified the alpha cell dendritic field area, the number of dendritic branch points, and the average dendritic length between branch points. According to the alpha cell location, the data were collected in three groups representing the retinal center, midperiphery, and far periphery, respectively. The data were then correlated with the postnatal retinal expansion which is known to differ among the above topographic regions of the retinae (Reichenbach et al., 1993). Our results show that the growth of alpha ganglion cell dendrites is not proportional to, but significantly exceeds, that of the local retinal tissue. Between P 8/9 and adulthood, the area of central alpha cells increases almost six-fold from 26,000 to 144,000 μm2 (retinal expansion: 2.2-fold), and that of peripheral cells more than 15-fold from 35,000 to 556,000 μm2 (retinal expansion: four-fold). During this period, the coverage factor of alpha cell dendritic fields increases about three-fold, and reaches adult levels of about 3 (retinal center) and 2.2 (periphery), respectively. The number of dendritic branch points remains nearly constant, and the distance between them increases by a factor close to the square root of the factor by which the dendritic field area grows. Thus, it appears that, from the second postnatal week on, dendritic trees of rabbit alpha ganglion cells increase by intense “interstitial growth,” rather than by outgrowth of (new) dendritic branches. This growth pattern is different from that of some other rabbit retinal ganglion cell types, and of alpha ganglion cells of the cat retina, whose dendritic trees expand at a rate equal to or less than that of the surrounding retinal tissue. The consequences for synaptic contacts with bipolar and amacrine cells are discussed; they suggest a high degree of synaptic plasticity during normal postnatal retinal growth.
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Tóth, Pál, and Charles Straznicky. "The morphological characterization and distribution of displaced ganglion cells in the anuran retina." Visual Neuroscience 3, no. 6 (December 1989): 551–61. http://dx.doi.org/10.1017/s0952523800009883.
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AbstractThe number, dendritic morphology, and retinal distribution of displaced ganglion cells were studied in two anuran species, Xenopus laevis and Bufo marinus. Horseradish peroxidase or cobaltic lysine complex was applied to the cut end of the optic nerve, and the size, shape, and retinal position of retrogradely filled ganglion cells displaced into the inner nuclear layer were determined in retinal wholemount and sectioned material. Approximately 1% of ganglion cells in Xenopus and 0.1% in Bufo were found to be displaced. In both species, many of the previously described orthotopic ganglion cell types (Straznicky & Straznicky, 1988; Straznicky et al., 1990) were present among displaced ganglion cells. In Xenopus more displaced ganglion cells were found in the retinal periphery than in the retinal center, and they formed 3 or 4 distinct bands around the optic nerve head. In Bufo the incidence of displaced ganglion cells was higher along the visual streak than in the dorsal and ventral peripheral retina. These results indicate that the distribution of displaced ganglion cells approximates the retinal distribution of orthotopic ganglion cells. One of the likely mechanisms to account for this developmental paradox may be that the formation of the inner plexiform layer, adjacent to the ciliary margin, acts as a mechanical barrier by preventing the entry of some of the late developing ganglion cells into the ganglion cell layer.
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Wu, Yihui, Jin Qiu, Shuilian Chen, Xi Chen, Jing Zhang, Jiejie Zhuang, Sian Liu, et al. "Comparison of the Response to the CXCR4 Antagonist AMD3100 during the Development of Retinal Organoids Derived from ES Cells and Zebrafish Retina." International Journal of Molecular Sciences 23, no. 13 (June 25, 2022): 7088. http://dx.doi.org/10.3390/ijms23137088.
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Retinal organoids generated from human embryonic stem cells or iPSCs recreate the key structural and functional features of mammalian retinal tissue in vitro. However, the differences in the development of retinal organoids and normal retina in vivo are not well defined. Thus, in the present study, we analyzed the development of retinal organoids and zebrafish retina after inhibition of CXCR4, a key role in neurogenesis and optic nerve development, with the antagonist AMD3100. Our data indicated that CXCR4 was mainly expressed in ganglion cells in retinal organoids and was rarely expressed in amacrine or photoreceptor cells. AMD3100 treatment reduced the retinal organoid generation ratio, impaired differentiation, and induced morphological changes. Ganglion cells, amacrine cells, and photoreceptors were decreased and abnormal locations were observed in organoids treated with AMD3100. Neuronal axon outgrowth was also damaged in retinal organoids. Similarly, a decrease of ganglion cells, amacrine cells, and photoreceptors and the distribution of neural outgrowth was induced by AMD3100 treatment in zebrafish retina. However, abnormal photoreceptor ensembles induced by AMD3100 treatment in the organoids were not detected in zebrafish retina. Therefore, our study suggests that although retinal organoids might provide a reliable model for reproducing a retinal developmental model, there is a difference between the organoids and the retina in vivo.
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Yan, Qi, E. Helene Sage, and Anita E. Hendrickson. "SPARC Is Expressed by Ganglion Cells and Astrocytes in Bovine Retina." Journal of Histochemistry & Cytochemistry 46, no. 1 (January 1998): 3–10. http://dx.doi.org/10.1177/002215549804600102.
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SPARC (secreted protein, acidic and rich in cysteine)/osteonectin is a matricellular, counteradhesive glycoprotein that disrupts cell-matrix interactions, interacts with growth factors and components of extracellular matrix, and modulates the cell cycle, but appears to subserve only minor structural roles. SPARC is expressed in a variety of tissues during embryogenesis and remodeling and is believed to regulate vascular morphogenesis and cellular differentiation. Although usually limited in normal adult tissues, SPARC is expressed at significant levels in the adult central nervous system. Using a monoclonal antibody against bovine bone osteonectin, we have determined the localization of SPARC in newborn (3-day-old) and adult (4–8-year-old) normal bovine retinas. SPARC was present in the soma of ganglion cells and strong reactivity was found in ganglion cell axons. Muller cells displayed no immunoreactivity, but SPARC was present in retinal astrocytes that were identified by the astrocyte marker glial fibrillary acidic protein (GFAP). Newborn calf retina showed a staining pattern similar to that of adult retina but exhibited significantly reduced levels of SPARC. Minimal levels of SPARC protein were also detected in some capillaries of the inner retina of both newborn and adult animals, whereas large vessels were negative. The presence of SPARC in the retina was confirmed by Western blotting of retinal extracts. These data indicate that SPARC originating from both neurons and glia of the inner retina may be an important modulator of retinal angiogenesis. The increased expression of SPARC in adult relative to newborn retinal tissue also indicates that SPARC has an ongoing role in the maintainance of retinal functions.
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Cessac, Bruno. "Retinal Processing: Insights from Mathematical Modelling." Journal of Imaging 8, no. 1 (January 17, 2022): 14. http://dx.doi.org/10.3390/jimaging8010014.
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The retina is the entrance of the visual system. Although based on common biophysical principles, the dynamics of retinal neurons are quite different from their cortical counterparts, raising interesting problems for modellers. In this paper, I address some mathematically stated questions in this spirit, discussing, in particular: (1) How could lateral amacrine cell connectivity shape the spatio-temporal spike response of retinal ganglion cells? (2) How could spatio-temporal stimuli correlations and retinal network dynamics shape the spike train correlations at the output of the retina? These questions are addressed, first, introducing a mathematically tractable model of the layered retina, integrating amacrine cells’ lateral connectivity and piecewise linear rectification, allowing for computing the retinal ganglion cells receptive field together with the voltage and spike correlations of retinal ganglion cells resulting from the amacrine cells networks. Then, I review some recent results showing how the concept of spatio-temporal Gibbs distributions and linear response theory can be used to characterize the collective spike response to a spatio-temporal stimulus of a set of retinal ganglion cells, coupled via effective interactions corresponding to the amacrine cells network. On these bases, I briefly discuss several potential consequences of these results at the cortical level.
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McCabe, K. L., E. C. Gunther, and T. A. Reh. "The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation." Development 126, no. 24 (December 15, 1999): 5713–24. http://dx.doi.org/10.1242/dev.126.24.5713.
Full textAbstract:
Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 μm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.
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Mure, Ludovic S., Frans Vinberg, Anne Hanneken, and Satchidananda Panda. "Functional diversity of human intrinsically photosensitive retinal ganglion cells." Science 366, no. 6470 (December 5, 2019): 1251–55. http://dx.doi.org/10.1126/science.aaz0898.
Full textAbstract:
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non–image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs’ photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.
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DIEDRICH, ERICH, and FRANK SCHAEFFEL. "Spatial resolution, contrast sensitivity, and sensitivity to defocus of chicken retinal ganglion cells in vitro." Visual Neuroscience 26, no. 5-6 (November 2009): 467–76. http://dx.doi.org/10.1017/s0952523809990253.
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AbstractThe chicken has been extensively studied as an animal model for myopia because its eye growth is tightly controlled by visual experience. It has been found that the retina controls the axial eye growth rates depending on the amount and the sign of defocus imposed in the projected image. Glucagonergic amacrine cells were discovered that appear to encode for the sign of imposed defocus. It is not clear whether the downstream neurons, the retinal ganglion cells, still have access to this information—and whether it ultimately reaches the brain. We have analyzed the spike rates of chicken retinal ganglion cells in vitro using a microelectrode array. For this purpose, we initially defined spatial resolution and contrast sensitivity in vitro. Two classes of chicken retinal ganglions were found, depending on the linearity of their responses with increasing contrast. Responses generally declined with increasing defocus of the visual stimulus. These responses were well predicted by the modulation transfer function for a diffraction-limited defocused optical system, the first Bessel function. Thus, the studied retinal ganglion cells did not distinguish between a loss of contrast at a given spatial frequency due to reduced contrast of the stimulus pattern or because the pattern was presented out of focus. Furthermore, there was no indication that the retinal ganglion cells responded differently to defocus of either sign, at least for the cells that were recorded in this study.
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MIDDLETON, T. P., and D. A. PROTTI. "Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells." Visual Neuroscience 28, no. 5 (July 12, 2011): 393–402. http://dx.doi.org/10.1017/s0952523811000198.
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AbstractThe endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14–P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.
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Choi, Hannah, Lei Zhang, Mark S. Cembrowski, Carl F. Sabottke, Alexander L. Markowitz, Daniel A. Butts, William L. Kath, Joshua H. Singer, and Hermann Riecke. "Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina." Journal of Neurophysiology 112, no. 6 (September 15, 2014): 1491–504. http://dx.doi.org/10.1152/jn.00437.2014.
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In many forms of retinal degeneration, photoreceptors die but inner retinal circuits remain intact. In the rd1 mouse, an established model for blinding retinal diseases, spontaneous activity in the coupled network of AII amacrine and ON cone bipolar cells leads to rhythmic bursting of ganglion cells. Since such activity could impair retinal and/or cortical responses to restored photoreceptor function, understanding its nature is important for developing treatments of retinal pathologies. Here we analyzed a compartmental model of the wild-type mouse AII amacrine cell to predict that the cell's intrinsic membrane properties, specifically, interacting fast Na and slow, M-type K conductances, would allow its membrane potential to oscillate when light-evoked excitatory synaptic inputs were withdrawn following photoreceptor degeneration. We tested and confirmed this hypothesis experimentally by recording from AIIs in a slice preparation of rd1 retina. Additionally, recordings from ganglion cells in a whole mount preparation of rd1 retina demonstrated that activity in AIIs was propagated unchanged to elicit bursts of action potentials in ganglion cells. We conclude that oscillations are not an emergent property of a degenerated retinal network. Rather, they arise largely from the intrinsic properties of a single retinal interneuron, the AII amacrine cell.
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Jensen, Ralph J. "Potassium-evoked directionally selective responses from rabbit retinal ganglion cells." Visual Neuroscience 13, no. 4 (July 1996): 705–19. http://dx.doi.org/10.1017/s0952523800008592.
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AbstractPrevious studies have shown that directionally selective (DS) retinal ganglion cells cannot only discriminate the direction of a moving object but they can also discriminate the sequence of two flashes of light at neighboring locations in the visual field: that is, the cells elicit a DS response to both real and apparent motion. This study examines whether a DS response can be elicited in DS ganglion cells by simply stimulating two neighboring areas of the retina with high external K+. Extracellular recordings were made from ON-OFF DS ganglion cells in superfused rabbit retinas, and the responses of these cells to focal applications of 100 mM KCl to the vitreal surface of the retina were measured. All cells produced a burst of spikes (typically lasting 50–200 ms) when a short pulse (10–50 ms duration) of KCl was ejected from the tip of a micropipette that was placed within the cell's receptive field. When KCl was ejected successively from the tips of two micropipettes that were aligned along the preferred-null axis of a cell, sequence-dependent responses were observed. The response to the second micropipette was suppressed when mimicking motion in the cell's null direction, whereas an enhancement during apparent motion in the opposite direction frequently occurred. Sequence discrimination in these cells was eliminated by the GABA antagonist picrotoxin and by the Ca2+-channel blocker ω-conotoxin MVIIC, two drugs that are known to abolish directional selectivity in these ganglion cells. The spatiotemporal properties of the K+-evoked sequence-dependent responses are described and compared with previous findings on apparent motion responses of ON-OFF DS ganglion cells.
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Hu, Yue, Lynn Michelle Grodzki, Susanne Bartsch, and Udo Bartsch. "Cell-Based Neuroprotection of Retinal Ganglion Cells in Animal Models of Optic Neuropathies." Biology 10, no. 11 (November 15, 2021): 1181. http://dx.doi.org/10.3390/biology10111181.
Full textAbstract:
Retinal ganglion cells (RGCs) comprise a heterogenous group of projection neurons that transmit visual information from the retina to the brain. Progressive degeneration of these cells, as it occurs in inflammatory, ischemic, traumatic or glaucomatous optic neuropathies, results in visual deterioration and is among the leading causes of irreversible blindness. Treatment options for these diseases are limited. Neuroprotective approaches aim to slow down and eventually halt the loss of ganglion cells in these disorders. In this review, we have summarized preclinical studies that have evaluated the efficacy of cell-based neuroprotective treatment strategies to rescue retinal ganglion cells from cell death. Intraocular transplantations of diverse genetically nonmodified cell types or cells engineered to overexpress neurotrophic factors have been demonstrated to result in significant attenuation of ganglion cell loss in animal models of different optic neuropathies. Cell-based combinatorial neuroprotective approaches represent a potential strategy to further increase the survival rates of retinal ganglion cells. However, data about the long-term impact of the different cell-based treatment strategies on retinal ganglion cell survival and detailed analyses of potential adverse effects of a sustained intraocular delivery of neurotrophic factors on retina structure and function are limited, making it difficult to assess their therapeutic potential.
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Kielczewski, Jennifer, Reiko Horai, and Rachel Caspi. "Retina-specific T cells provide neuroprotection in a mouse model of glaucoma (BA6P.140)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 114.21. http://dx.doi.org/10.4049/jimmunol.194.supp.114.21.
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Abstract Glaucoma is a disease that leads to degeneration of retinal ganglion cells (RGC) and is potentially blinding if left untreated. Based on the concept of “beneficial autoimmunity”, we examined whether naïve, retina-specific T lymphocytes can provide neuroprotection to retinal ganglion cells in an optic nerve crush injury glaucoma model. Purified T cells from mice that express the transgenic R161H TCR for the retinal antigen IRBP, as well as eGFP (R161H-eGFP), were adoptively transferred into wild type (WT) mice. Also, irradiated bone marrow (BM) chimeras were stably engrafted with <10% circulating R161H-eGFP cells. Recipient mice were subjected to retrograde fluorogold labeling for quantification of RGC prior to an optic nerve crush injury. Retinas were imaged 4 or 7 days later for quantification of RGCs and donor R161H-eGFP T cells were detected by confocal microscopy. In both types of recipients, T cell influx into the eye and neuroprotection were apparent, but differed in kinetics. In adoptively transferred mice, R161H T cells were detected in the eye 4 days post injury and were associated with 27% less RGC loss compared to controls infused with normal polyclonal eGFP+ T cells (p<0.05). In the BM chimeric mice, major influx of R161H-eGFP cells occurred at 7 days post injury and was associated with a 16% statistically significant reduction in RGC loss. We conclude that naïve retina-specific T cells can mediate neuroprotection of retinal ganglion cells.
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MARGALIT, EYAL, NORBERT BABAI, JIANMIN LUO, and WALLACE B. THORESON. "Inner and outer retinal mechanisms engaged by epiretinal stimulation in normal and rd mice." Visual Neuroscience 28, no. 2 (March 2011): 145–54. http://dx.doi.org/10.1017/s0952523810000489.
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AbstractRetinal prosthetic devices are being developed to bypass degenerated retinal photoreceptors by directly activating retinal neurons with electrical stimulation. However, the retinal circuitry that is activated by epiretinal stimulation is not well characterized. Whole-cell patch clamp recordings were obtained from ganglion cells in normal and rd mice using flat-mount and retinal slice preparations. A stimulating electrode was positioned along the ganglion cell side of the preparation at different distances from the stimulated tissue. Pulses of cathodic current evoked action potentials in ganglion cells and less frequently evoked sustained inward currents that appeared synaptic in origin. Sustained currents reversed around ECl and were inhibited by blockade of α-amino-3-hydroxyl-5-methyl-4-isoxazole-proprionate (AMPA)-type glutamate receptors with 2,3-dihydroxy-6-nitro-sulfamoyl-benzo(f)-quinoxaline-2,3-dione (NBQX), γ aminobutyric acid a/c (GABAa/c) receptors with picrotoxinin, or glycine receptors with strychnine. This suggests that epiretinal stimulation activates glutamate release from bipolar cell terminals, which in turn evokes release of GABA and glycine from amacrine cells. Synaptic current thresholds were lower in ON ganglion cells than OFF cells, but the modest difference did not attain statistical significance. Synaptic currents were rarely observed in rd mice lacking photoreceptors compared to normal retina. In addition, confocal calcium imaging experiments in normal mice retina slices revealed that epiretinal stimulation evoked calcium increases in the outer plexiform layer. These results imply a contribution from photoreceptor inputs to the synaptic currents observed in ganglion cells. The paucity of synaptic responses in rd mice retina slices suggests that it is better to target retinal ganglion cells directly rather than to attempt to engage the inner retinal circuitry.
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JENSEN, RALPH J. "Responses of directionally selective retinal ganglion cells to activation of AMPA glutamate receptors." Visual Neuroscience 16, no. 2 (March 1999): 205–19. http://dx.doi.org/10.1017/s0952523899162023.
Full textAbstract:
Previous studies in the rabbit retina have shown that drugs which block AMPA glutamate receptors abolish directional selectivity in ON–OFF directionally selective (DS) ganglion cells. The effects of activation of AMPA receptors on the directionally selective responses of these ganglion cells had not been studied. In the present study, extracellular recordings of the responses of ON–OFF DS ganglion cells to a moving bar of light were made in an in vitro rabbit retinal preparation. In control solution, bath application of AMPA (7–10 μM) abolished the light responses of most ON–OFF DS ganglion cells. On washout of AMPA, the light responses rapidly returned; however, the cells temporarily lost the ability to discriminate the direction of the moving bar of light. That is, the cells responded equally to movement in the preferred and null directions. Pretreatment of retinas with the glycine receptor antagonist strychnine (1–2 μM) did not alter the effects of AMPA. On the other hand, in retinas pretreated with the GABAA receptor antagonist SR95531 (0.2–0.25 μM), AMPA did not abolish the light responses of ON–OFF DS ganglion cells but instead abolished directional selectivity in these cells by bringing out a response to movement in the null direction. This finding suggests that an AMPA-induced GABA efflux from cells in the retina was responsible for the suppression of the light responses by AMPA. In control solution, application of the selective AMPA receptor agonist (S)-5-fluorowillardiine (2–3 μM) only temporarily abolished the light responses of ON–OFF DS ganglion cells. As the light responses returned, it was clear that directional selectivity had been abolished by (S)-5-fluorowillardiine. In control solution, blocking AMPA receptor desensitization with cyclothiazide (80–100 μM) greatly reduced the light responses of ON–OFF DS ganglion cells. As the light responses slowly returned on washout of cyclothiazide, directional selectivity was clearly reduced although not abolished. In retinas pretreated with SR95531, application of cyclothiazide abolished directional selectivity. Diazoxide (700–1000 μM), another blocker of AMPA receptor desensitization, abolished directional selectivity in ON–OFF DS ganglion cells without the need of adding SR95531 to the bathing solution. It is concluded that, in the rabbit retina, AMPA receptors play an important role in generating directional selectivity in ON–OFF DS ganglion cells. Moreover, excessive activation of AMPA receptors greatly compromises the mechanism for directional selectivity in ON–OFF DS ganglion cells.
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Shou, T., A. G. Leventhal, K. G. Thompson, and Y. Zhou. "Direction biases of X and Y type retinal ganglion cells in the cat." Journal of Neurophysiology 73, no. 4 (April 1, 1995): 1414–21. http://dx.doi.org/10.1152/jn.1995.73.4.1414.
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1. It has been reported that in the cat only a specialized group of retinal ganglion cells constituting approximately 1% of the overall population are direction sensitive. Two major groups of retinal ganglion cells, the X and Y cells, have been reported not to be sensitive to the direction of stimulus motion. 2. We recorded action potentials of retinal ganglion cells intraocularly. We studied quantitatively the visual responses elicited by drifting sinusoidal gratings of various spatial frequencies, bars, and spots. 3. The results confirm previous reports that most cat retinal ganglion cells exhibit orientation biases when tested with gratings of relatively high spatial frequency. 4. Additionally, we find that 22% of X and 34% of Y type retinal ganglion cells exhibit direction biases. Overall, Y cells displayed significantly stronger direction biases than did X cells. 5. In general, direction biases are clearest when the test gratings are of relatively low spatial frequency. 6. The direction biases of X and Y cells subserving the central 15 degrees of retina were weaker than those of cells subserving more peripheral regions. 7. The direction-biased responses of cat ganglion cells were similar to those of X and Y type relay cells in the cat dorsal lateral geniculate nucleus (LGNd). Thus we suggest that the direction biases of LGNd cells are a reflection of their retinal inputs.
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Liu, Hanhan, and Verena Prokosch. "Energy Metabolism in the Inner Retina in Health and Glaucoma." International Journal of Molecular Sciences 22, no. 7 (April 1, 2021): 3689. http://dx.doi.org/10.3390/ijms22073689.
Full textAbstract:
Glaucoma, the leading cause of irreversible blindness, is a heterogeneous group of diseases characterized by progressive loss of retinal ganglion cells (RGCs) and their axons and leads to visual loss and blindness. Risk factors for the onset and progression of glaucoma include systemic and ocular factors such as older age, lower ocular perfusion pressure, and intraocular pressure (IOP). Early signs of RGC damage comprise impairment of axonal transport, downregulation of specific genes and metabolic changes. The brain is often cited to be the highest energy-demanding tissue of the human body. The retina is estimated to have equally high demands. RGCs are particularly active in metabolism and vulnerable to energy insufficiency. Understanding the energy metabolism of the inner retina, especially of the RGCs, is pivotal for understanding glaucoma’s pathophysiology. Here we review the key contributors to the high energy demands in the retina and the distinguishing features of energy metabolism of the inner retina. The major features of glaucoma include progressive cell death of retinal ganglions and optic nerve damage. Therefore, this review focuses on the energetic budget of the retinal ganglion cells, optic nerve and the relevant cells that surround them.
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Mass, Alla M., and Alexander Ya Supin. "Ganglion Cell Topography and Retinal Resolution in an Irrawaddy Dolphin (Orcaella brevirostris)." Aquatic Mammals 48, no. 1 (January 15, 2022): 68–74. http://dx.doi.org/10.1578/am.48.1.2022.68.
Full textAbstract:
The topographic distribution of retinal ganglion cells was investigated in a retinal wholemount of an Irrawaddy dolphin (Orcaella brevirostris). Two zones of increased concentration of ganglion cells were observed—one in the temporal segment and the other in the nasal segment of the retina. The maximal cell concentration was 250 cell/mm2 in the temporal area and 194 cell/mm2 in the nasal area. Based on the posterior nodal distance of 11 mm, the resolution was evaluated as 19.8 arc min in the temporal retinal area (the frontal visual field) and 22.4 arc min in the nasal retinal area (the temporal visual field). Among retinal ganglion cells, a group of giant cells that ranged from 42 to 52 µm in diameter were observed; these cells represented 8% of the total population. The obtained data allowed us to suggest that the presence of two areas of concentrated ganglion cells is characteristic of many delphinids inhabiting both clear oceanic waters or turbid river waters, whereas low ganglion cell density is associated with optic properties of the media.
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Tabata, Yoko, Yasuo Ouchi, Haruyuki Kamiya, Toshiya Manabe, Ken-ichi Arai, and Sumiko Watanabe. "Specification of the Retinal Fate of Mouse Embryonic Stem Cells by Ectopic Expression of Rx/rax, a Homeobox Gene." Molecular and Cellular Biology 24, no. 10 (May 15, 2004): 4513–21. http://dx.doi.org/10.1128/mcb.24.10.4513-4521.2004.
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ABSTRACT With the goal of generating retinal cells from mouse embryonic stem (ES) cells by exogenous gene transfer, we introduced the Rx/rax transcription factor, which is expressed in immature retinal cells, into feeder-free mouse ES cells (CCE). CCE cells expressing Rx/rax as well as enhanced green fluorescent protein (CCE-RX/E cells) proliferated and remained in the undifferentiated state in the presence of leukemia inhibitory factor, as did parental ES cells. We made use of mouse embryo retinal explant cultures to address the differentiation ability of grafted ES cells. Dissociated embryoid bodies were treated with retinoic acid for use as donor cells and cocultured with retina explants for 2 weeks. In contrast to the parental CCE cells, which could not migrate into host retinal cultures, CCE-RX/E cells migrated into the host retina and extended their process-like structures between the host retinal cells. Most of the grafted CCE-RX/E cells became located in the ganglion cell and inner plexiform layers and expressed ganglion and horizontal cell markers. Furthermore, these grafted cells had the electrophysiological properties expected of ganglion cells. Our data thus suggest that subpopulations of retinal neurons can be generated in retinal explant cultures from grafted mouse ES cells ectopically expressing the transcription factor Rx/rax.
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Stuermer, Claudia A. O. "Pathways of regenerated retinotectal axons in goldfish." Development 93, no. 1 (April 1, 1986): 1–28. http://dx.doi.org/10.1242/dev.93.1.1.
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This study investigates the order of regenerating retinal axons in the goldfish. The spatiotemporal pattern of axon regrowth was assessed by applying horseradish peroxidase (HRP) to regenerating axons in the optic tract at various times after optic nerve section and by analysing the distribution of retrogradely labelled ganglion cells in retina. At all regeneration stages labelled ganglion cells were widely distributed over the retina. There was no hint that axons from central (older) ganglion cells might regrow earlier, and peripheral (younger) ganglion cells later, as occurs in normal development. The absence of an age-related ordering in the regenerated optic nerve was demonstrated by labelling a few axon bundles intraorbitally with HRP (Easter, Rusoff & Kish, 1981) caudal to the previous cut. The retrogradely labelled cells in retina were randomly distributed in regenerates andnot clustered in annuli as in normals. Tracing regenerating axons which were stained anterogradelyfrom intraretinal HRP applications or retrogradely from single labelled tectal fascicles illustrated the fact that the regenerating axons coursed in abnormal routes in the optic nerve and tract. On the surface of the tectum regenerated fibres re-established a fascicle fan. The retinal origin of tectal fascicles was assessed by labelling individual peripheral, intermediate and rostral fascicles with HRP. The retrogradely labelled ganglion cells in the retina were often more widely distributed than in normals, but were mostly found in peripheral, intermediate and central retina, respectively. The order of fibre departure from each tectal fascicle was revealed by placing HRP either on the fascicle's proximal or on its distal half. With proximal labelling sites labelled ganglion cells were found in the temporal and nasal retina, and with distal labelling sites labelled ganglion cells were confined to nasal retina only. Further, the axonal trajectories of anterogradely labelled dorsotemporal retinal ganglion cells were compared to those of dorsonasal retinal ganglion cells in tectal whole mounts. Dorsotemporal axons were confined to the rostral tectal half, whereas dorsonasal axons followed fascicular routes into the fascicles' distal end and reached into caudal tectum. This suggests that the fibres exited along their fascicle's course in a temporonasal sequence. Thus in the tectum, fibres in fascicles restore a gross spatial and age-related order and tend to follow their normal temporonasal sequence of exit.
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Strang, Christianne E., Margot E. Andison, Franklin R. Amthor, and Kent T. Keyser. "Rabbit retinal ganglion cells express functional α7 nicotinic acetylcholine receptors." American Journal of Physiology-Cell Physiology 289, no. 3 (September 2005): C644—C655. http://dx.doi.org/10.1152/ajpcell.00633.2004.
Full textAbstract:
It is well known that cholinergic agents affect ganglion cell (GC) firing rates and light responses in the retinas of many species, but the specific receptor subtypes involved in mediating these effects have been only partially characterized. We sought to determine whether functional α7 nicotinic acetylcholine receptors (nAChRs) contribute to the responses of specific retinal GC classes in rabbit retina. We used electrophysiology, pharmacology, immunohistochemistry, and reverse transcriptase-polymerase chain reaction to determine the pharmacological properties and expression of nAChR subtypes by specific rabbit retinal GC classes. Choline was used as an α7 nAChR agonist. Methyllycaconitine (MLA) was used as a competitive α7 nAChR antagonist. The application of choline before synaptic blockade resulted in changes in retinal GC activity, including increases or decreases in maintained firing and/or enhancement or suppression of light responses. Many physiologically identified GC types, including sustained off, sustained on, transient off, and transient on cells, demonstrated responses to choline application while under synaptic blockade. The choline-induced responses could be blocked with MLA, confirming α7 nAChR activation. Individual choline-responsive GCs displayed mRNA transcripts consistent with the expression of functional α7 nAChRs. Other GCs demonstrated physiological responses and mRNA expression consistent with the expression of both α7 and non-α7 nAChRs. Thus mRNA is present for multiple nAChR subunits in whole retina extracts, and functional α7 nAChRs are capable of modulating the responses of GCs in adult rabbit retina. We also demonstrate through physiological responses that subsets of GCs express more than one nAChR subtype.
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Peichl, Leo. "Alpha ganglion cells in mammalian retinae: Common properties, species differences, and some comments on other ganglion cells." Visual Neuroscience 7, no. 1-2 (August 1991): 155–69. http://dx.doi.org/10.1017/s0952523800011020.
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AbstractA specific morphological class of ganglion cell, the alpha cell, was first defined in cat retina. Alpha cells have since been found in a wide range of mammalian retinae, including several orders of placental and marsupial mammals. Characteristically, they have the largest somata and a large dendritic field with a typical branching pattern. They occur as inner and outer stratifying subpopulations, presumably corresponding to ON-center and OFF-center receptive fields. In all species, alpha cells account for less than 10% of the ganglion cells, their somata are regularly spaced, and their dendritic fields evenly and economically cover the retina in a mosaic-like fashion. The morphology of alpha cells and many features, both of single cells and of the population, are conserved across species with different habitats and life-styles. This suggests that alpha cells are a consistent obligatory ganglion cell type in every mammalian retina and probably subserve some fundamental task(s) in visual performance.Some general rules about the construction principles of ganglion cell classes are inferred from the alpha cells, stressing the importance of population parameters for the definition of a class. The principle, that a functionally and morphologically homogeneous population should have a regular arrangement and a complete and even coverage of the retina to perform its part in image processing at each retinal location, is especially evident across species and across ganglion cell types.
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Khatib, T. Z., and K. R. Martin. "Protecting retinal ganglion cells." Eye 31, no. 2 (January 13, 2017): 218–24. http://dx.doi.org/10.1038/eye.2016.299.
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LITHERLAND, LENORE, SHAUN P. COLLIN, and KERSTIN A. FRITSCHES. "Eye growth in sharks: Ecological implications for changes in retinal topography and visual resolution." Visual Neuroscience 26, no. 4 (July 2009): 397–409. http://dx.doi.org/10.1017/s0952523809990150.
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AbstractThe visual abilities of sharks show substantial interspecific variability. In addition, sharks may change their habitat and feeding strategy throughout life. As the eyes of sharks continue to grow throughout the animal’s lifetime, ontogenetic variability in visual ability may also occur. The topographic analysis of the photoreceptor and ganglion cell distributions can identify visual specializations and assess changes in visual abilities that may occur concurrently with eye growth. This study examines an ontogenetic series of whole-mounted retinas in two elasmobranch species, the sandbar shark, Carcharhinus plumbeus, and the shortspine spurdog, Squalus mitsukurii, to identify regional specializations mediating zones for improved spatial resolution. The study examines retinal morphology and presents data on summation ratios between photoreceptor and ganglion cell layers, anatomically determined peak spatial resolving power, and the angular extent of the visual field. Peak densities of photoreceptors and ganglion cells occur in similar retinal locations. The topographic distribution of neurons in the ganglion cell layer does not differ substantially with eye growth. However, predicted peak spatial resolution increases with eye growth from 4.3 to 8.9 cycles/deg in C. plumbeus and from 5.7 to 7.2 cycles/deg in S. mitsukurii. The topographic distribution of different-sized ganglion cells is also mapped in C. plumbeus, and a population of large ganglion cells (soma area 120–350 μm2) form a narrow horizontal streak across the retinal meridian, while the spatial distribution of ordinary-sized ganglion cells (soma area 30–120 μm2) forms an area in the central retina. Species-specific retinal specializations highlight differences in visually mediated behaviors and foraging strategies between C. plumbeus and S. mitsukurii.
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Reichenbach, A., J. Schnitzer, E. Reichelt, N. N. Osborne, B. Fritzsche, A. Puls, U. Richter, et al. "Development of the rabbit retina, III: Differential retinal growth, and density of projection neurons and interneurons." Visual Neuroscience 10, no. 3 (May 1993): 479–98. http://dx.doi.org/10.1017/s0952523800004703.
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AbstractTo provide a quantitative description of postnatal retinal expansion in rabbits, a new procedure was developed to map the retinae, which cover the inner surface of hemispheres or parts of rotation ellipsoids, in situ, onto a single plane. This method, as well as the known distribution of Müller cells per unit retinal surface area, were used to estimate the redistribution of specific subpopulations of Müller cells within different topographic regions of the retinae. Müller cells are known to exist as a stable population of cells 1 week after birth and can therefore be used as “markers” for determining tissue expansion. Our results show that differential retinal expansion occurs during development. Peripheral retinal regions expand at least twice as much as the central ones. Furthermore, there is a greater vertical than horizontal expansion. This differential retinal expansion leads to a corresponding redistribution of 5-hydroxytryptamine (5-HT) accumulating amacrine cells. Differential retinal expansion, however, does not account for all of the changes in the centro-peripheral density gradient of cells in the ganglion cell layer (GCL) — mostly retinal ganglion cells — during postnatal development. The changes in the ganglion cell layer were evaluated in Nissl-stained wholemount retinal preparations. Additionally, the difference between expansion-related redistribution of cells in the GCL and Müller cells was confirmed in wholemount preparations where Müller cells (identified as vimentin positive) and cells in the GCL (identified by fluorescent supravital dyes) were simultaneously labeled. It is assumed that many of the ganglion cells within the retinal center are not translocated during retinal expansion, possibly because their axons are fixed. In contrast, 5-HT accumulating amacrine cells — which are interneurons without a retinofugal axon — display a passive redistribution together with the surrounding retinal tissue.
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Benardete, Ethan A., Ehud Kaplan, and Bruce W. Knight. "Contrast gain control in the primate retina: P cells are not X-like, some M cells are." Visual Neuroscience 8, no. 5 (May 1992): 483–86. http://dx.doi.org/10.1017/s0952523800004995.
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AbstractPrimate retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus (M) are much more sensitive to luminance contrast than those ganglion cells projecting to the parvocellular layers (P). We now report that increasing contrast modifies the temporal-frequency response of M cells, but not of P cells. With rising contrast, the M cells' responses to sinusoidal stimuli show an increasing attenuation at low temporal frequencies while the P cells' responses scale uniformly. The characteristic features of M-cell dynamics are well described by a model originally developed for the X and Y cells of the cat, where the hypothesized nonlinear feedback mechanism responsible for this behavior has been termed the contrast gain control (Shapley & Victor, 1978, 1981; Victor, 1987, 1988). These data provide further physiological evidence that the M-cell pathway differs from the P-cell pathway with regard to the functional elements in the retina. Furthermore, the similarity in dynamics between primate M cells and cat X and Y retinal ganglion cells suggests the possibility that P cells, being different from either group, are a primate specialization not found in the retinae of lower mammals.
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DeVries, Steven H. "Correlated Firing in Rabbit Retinal Ganglion Cells." Journal of Neurophysiology 81, no. 2 (February 1, 1999): 908–20. http://dx.doi.org/10.1152/jn.1999.81.2.908.
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Correlated firing in rabbit retinal ganglion cells. A ganglion cell’s receptive field is defined as that region on the retinal surface in which a light stimulus will produce a response. While neighboring ganglion cells may respond to the same stimulus in a region where their receptive fields overlap, it generally has been assumed that each cell makes an independent decision about whether to fire. Recent recordings from cat and salamander retina using multiple electrodes have challenged this view of independent firing by showing that neighboring ganglion cells have an increased tendency to fire together within ±5 ms. However, there is still uncertainty about which types of ganglion cells fire together, the mechanisms that produce coordinated spikes, and the overall function of coordinated firing. To address these issues, the responses of up to 80 rabbit retinal ganglion cells were recorded simultaneously using a multielectrode array. Of the 11 classes of rabbit ganglion cells previously identified, coordinated firing was observed in five. Plots of the spike train cross-correlation function suggested that coordinated firing occurred through two mechanisms. In the first mechanism, a spike in an interneuron diverged to produce simultaneous spikes in two ganglion cells. This mechanism predominated in four of the five classes including the onbrisk transient cells. In the second mechanism, ganglion cells appeared to activate each other reciprocally. This was the predominant pattern of correlated firing in off brisk transient cells. By comparing the receptive field profiles of on andoff brisk transient cells, a peripheral extension of theoff brisk transient cell receptive field was identified that might be produced by lateral spike spread. Thus an individualoff brisk transient cell can respond both to a light stimulus directed at the center of its receptive field and to stimuli that activate neighboring off brisk transient cells through their receptive field centers.
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Frade, J. M., P. Bovolenta, J. R. Martinez-Morales, A. Arribas, J. A. Barbas, and A. Rodriguez-Tebar. "Control of early cell death by BDNF in the chick retina." Development 124, no. 17 (September 1, 1997): 3313–20. http://dx.doi.org/10.1242/dev.124.17.3313.
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The developing chick retina undergoes at least two discrete periods of programmed cell death. The earlier period coincides with the main onset of neuron birth and migration (embryonic day 5–7), whereas the latter one corresponds to the well-documented process of retinal ganglion cell death following tectal innervation (embryonic day 10–14; Rager, G. H. (1980) Adv. Anat. Embryol. Cell Biol. 63, 1–92). In the early period, apoptosis is induced by nerve growth factor (NGF) acting via its p75 receptor (Frade, J. M., Rodriguez-Tebar, A. and Barde, Y.-A. (1996) Nature 383, 166–168). Here, we show that the application of brain-derived neurotrophic factor (BDNF) to chick embryos in ovo prevented retinal cell death in the early period, whereas exogenously applied NGF and neurotrophin-3 had no such effect. The addition of BDNF to embryos resulted in about 70% increase in the number of retinal ganglion cells in both E6 and E9 retinas relative to controls. BDNF is first expressed in both the pigment epithelium and neural retina of embryonic day 4 embryos, and at the same stage of development, its TrkB receptor is expressed in the neural retina. Our data indicate that early cell death is an important process in the neurogenesis of retinal ganglion cells and is regulated by locally produced BDNF.
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Stanford, L. R. "X-cells in the cat retina: relationships between the morphology and physiology of a class of cat retinal ganglion cells." Journal of Neurophysiology 58, no. 5 (November 1, 1987): 940–64. http://dx.doi.org/10.1152/jn.1987.58.5.940.
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1. The morphology of 21 physiologically characterized X-cells in the cat retina was studied using intracellular recording and injection with horseradish peroxidase. The data from these experiments were used to test directly the relationships between specific structural and functional characteristics of a sample of individual retinal ganglion cells of the same anatomical and physiological class. Where possible, the response properties of 53 other retinal X-cells that were not successfully injected and recovered are compared with those of the labeled sample. These comparisons, which included conduction velocities (both intraretinal and extraretinal) and receptive-field size, indicate that the labeled X-cells are a representative sample of the population of retinal X-cells at corresponding eccentricities. 2. The somata of this group of injected retinal X-cells increase in size with increasing distance from the area centralis up to 13 degrees eccentricity (the greatest distance from the area centralis at which an X-cell was injected and recovered). The soma sizes of this sample of retinal ganglion cells range from 143.5 to 529.9 micron 2 (diam = 13.5-26.0 micron). Comparison of the soma sizes of the injected and recovered retinal X-cells with those of 300 Nissl-stained neurons at comparable eccentricities in the same retinae indicate that the injected sample had soma sizes that are consistent with their classification as "medium-sized" retinal ganglion cells (5, 69, 74). 3. All of the physiologically characterized retinal X-cells of this study have the compact dendritic arbors described to the morphological class of retinal ganglion cell called beta-cells by Boycott and Wassle (5). The dendrites of some of these neurons have many spinelike appendages, whereas those of other cells are nearly appendage free. We found no obvious correlation between the presence of dendritic appendages and any specific response characteristic ("ON-" or "OFF-center", etc). Like the size of the soma, both the diameter of the dendritic arbors of these cells, and the number of primary dendrites (those dendrites that originate directly from the soma), increase with increasing distance from the area centralis. 4. Since both morphological and physiological data were obtained for these neurons, it is possible to describe the relationship between the size of the receptive-field center and the diameter of the dendritic arbor for individual retinal ganglion cells. These comparisons show that the relationship between the anatomical measure and this response parameter for the entire sample of labeled X-cells is not as strong as had previously been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
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Weitz, Andrew C., Matthew R. Behrend, Nan Sook Lee, Ronald L. Klein, Vince A. Chiodo, William W. Hauswirth, Mark S. Humayun, James D. Weiland, and Robert H. Chow. "Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators." Journal of Neurophysiology 109, no. 7 (April 1, 2013): 1979–88. http://dx.doi.org/10.1152/jn.00852.2012.
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Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.
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Schwartz, Greg, and Michael J. Berry. "Sophisticated Temporal Pattern Recognition in Retinal Ganglion Cells." Journal of Neurophysiology 99, no. 4 (April 2008): 1787–98. http://dx.doi.org/10.1152/jn.01025.2007.
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Pattern recognition is one of the most important tasks of the visual system, and uncovering the neural mechanisms underlying recognition phenomena has been a focus of researchers for decades. Surprisingly, at the earliest stages of vision, the retina is capable of highly sophisticated temporal pattern recognition. We stimulated the retina of tiger salamander ( Ambystoma tigrinum) with periodic dark flash sequences and found that retinal ganglion cells had a wide variety of different responses to a periodic flash sequence with many firing when a flash was omitted. The timing of the omitted stimulus response (OSR) depended on the period, with individual cells tracking the stimulus period down to increments of 5 ms. When flashes occurred earlier than expected, cells updated their expectation of the next flash time by as much as 50 ms. When flashes occurred later than expected, cells fired an OSR and reset their temporal expectation to the average time interval between flashes. Using pharmacology to investigate the retinal circuitry involved, we found that inhibitory transmission from amacrine cells was not required, but on bipolar cells were required. The results suggest a mechanism in which the intrinsic resonance of on bipolars leads to the OSR in ganglion cells. We discuss the implications of retinal pattern recognition on the neural code of the retina and visual processing in general.
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Fairhall, Adrienne L., C. Andrew Burlingame, Ramesh Narasimhan, Robert A. Harris, Jason L. Puchalla, and Michael J. Berry. "Selectivity for Multiple Stimulus Features in Retinal Ganglion Cells." Journal of Neurophysiology 96, no. 5 (November 2006): 2724–38. http://dx.doi.org/10.1152/jn.00995.2005.
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Under normal viewing conditions, retinal ganglion cells transmit to the brain an encoded version of the visual world. The retina parcels the visual scene into an array of spatiotemporal features, and each ganglion cell conveys information about a small set of these features. We study the temporal features represented by salamander retinal ganglion cells by stimulating with dynamic spatially uniform flicker and recording responses using a multi-electrode array. While standard reverse correlation methods determine a single stimulus feature—the spike-triggered average—multiple features can be relevant to spike generation. We apply covariance analysis to determine the set of features to which each ganglion cell is sensitive. Using this approach, we found that salamander ganglion cells represent a rich vocabulary of different features of a temporally modulated visual stimulus. Individual ganglion cells were sensitive to at least two and sometimes as many as six features in the stimulus. While a fraction of the cells can be described by a filter-and-fire cascade model, many cells have feature selectivity that has not previously been reported. These reverse models were able to account for 80–100% of the information encoded by ganglion cells.
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Thompson, I. D., G. Jeffery, J. E. Morgan, and G. Baker. "Albino gene dosage and retinal decussation patterns in the pigmented ferrret." Visual Neuroscience 6, no. 4 (April 1991): 393–98. http://dx.doi.org/10.1017/s0952523800006623.
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AbstractWe have examined the retinal decussation patterns in pigmented ferrets that were either wild-type sable or heterozygous with one albino gene. Unilateral injections of horseradish peroxidase were made into the optic tract and labeled ganglion cells visualized in retinal wholemounts. In both wild-type and heterozygous ferrets, those ganglion cells in the temporal retina with the largest cell bodies projected only to the contralateral side of the brain. The total number of ipsilaterally projecting ganglion cells did not differ with the genotype of the animal. The numbers ranged from 5471–6759 cells. Unlike the cat, there is no difference in retinal decussation patterns in wild-type sable ferrets and heterozygous ferrets carrying one albino gene.