scholarly journals Cross inhibition from ON to OFF pathway improves the efficiency of contrast encoding in the mammalian retina

2012 ◽  
Vol 108 (10) ◽  
pp. 2679-2688 ◽  
Author(s):  
Zhiyin Liang ◽  
Michael A. Freed
Keyword(s):  
Spike Train ◽  
Ganglion Cells ◽  
Ideal Observer ◽  
Detection Accuracy ◽  
Low Contrast ◽  
Mammalian Retina ◽  
Ideal Observer Analysis ◽  
On And Off Pathways ◽  
Cross Inhibition

The retina is divided into parallel and mostly independent ON and OFF pathways, but the ON pathway “cross” inhibits the OFF pathway. Cross inhibition was thought to improve signal processing by the OFF pathway, but its effect on contrast encoding had not been tested experimentally. To quantify the effect of cross inhibition on the encoding of contrast, we presented a dark flash to an in vitro preparation of the mammalian retina. We then recorded excitatory currents, inhibitory currents, membrane voltages, and spikes from OFF α-ganglion cells. The recordings were subjected to an ideal observer analysis that used Bayesian methods to determine how accurately the recordings detected the dark flash. We found that cross inhibition increases the detection accuracy of currents and membrane voltages. Yet these improvements in encoding do not fully reach the spike train, because cross inhibition also hyperpolarizes the OFF α-cell below spike threshold, preventing small signals in the membrane voltages at low contrast from reaching the spike train. The ultimate effect of cross inhibition is to increase the accuracy with which the spike train detects moderate contrast, but reduce the accuracy with which it detects low contrast. In apparent compensation for the loss of accuracy at low contrast, cross inhibition, by hyperpolarizing the OFF α-cell, reduces the number of spikes required to detect the dark flash and thereby increases encoding efficiency.

scholarly journals Contrast Threshold of a Brisk-Transient Ganglion Cell In Vitro

2003 ◽  
Vol 89 (5) ◽  
pp. 2360-2369 ◽  
Author(s):  
Narender K. Dhingra ◽  
Yen-Hong Kao ◽  
Peter Sterling ◽  
Robert G. Smith
Keyword(s):  
Ganglion Cells ◽  
Probability Distributions ◽  
Linear Interpolation ◽  
Ideal Observer ◽  
In Vivo Studies ◽  
Contrast Threshold ◽  
Choice Procedure ◽  
Forced Choice Procedure

We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an “ideal observer” (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 ± 0.4% (SE); n = 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 ± 0.2%). Contrast increments above a very low “basal contrast” were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37°C and declined with a Q 10 of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.

scholarly journals Inhibitory input to the direction-selective ganglion cell is saturated at low contrast

2015 ◽  
Vol 114 (2) ◽  
pp. 927-941 ◽  
Author(s):  
Mikhail Y. Lipin ◽  
W. Rowland Taylor ◽  
Robert G. Smith
Keyword(s):  
Spike Train ◽  
Ganglion Cells ◽  
Signal To Noise Ratio ◽  
Temporal Correlation ◽  
Gaba Release ◽  
Inhibitory Input ◽  
Low Contrast ◽  
Preferred Direction ◽  
Wide Range ◽  
Starburst Amacrine Cell

Direction-selective ganglion cells (DSGCs) respond selectively to motion toward a “preferred” direction, but much less to motion toward the opposite “null” direction. Directional signals in the DSGC depend on GABAergic inhibition and are observed over a wide range of speeds, which precludes motion detection based on a fixed temporal correlation. A voltage-clamp analysis, using narrow bar stimuli similar in width to the receptive field center, demonstrated that inhibition to DSGCs saturates rapidly above a threshold contrast. However, for wide bar stimuli that activate both the center and surround, inhibition depends more linearly on contrast. Excitation for both wide and narrow bars was also more linear. We propose that positive feedback, likely within the starburst amacrine cell or its network, produces steep saturation of inhibition at relatively low contrast. This mechanism renders GABA release essentially contrast and speed invariant, which enhances directional signals for small objects and thereby increases the signal-to-noise ratio for direction-selective signals in the spike train over a wide range of stimulus conditions. The steep saturation of inhibition confers to a neuron immunity to noise in its spike train, because when inhibition is strong no spikes are initiated.

scholarly journals Sluggish and Brisk Ganglion Cells Detect Contrast With Similar Sensitivity

2005 ◽  
Vol 93 (5) ◽  
pp. 2388-2395 ◽  
Author(s):  
Ying Xu ◽  
Narender K. Dhingra ◽  
Robert G. Smith ◽  
Peter Sterling
Keyword(s):  
Visual Information ◽  
Dynamic Range ◽  
Ganglion Cells ◽  
Broad Class ◽  
Receptive Fields ◽  
Stimulus Frequency ◽  
Ideal Observer ◽  
Low Contrast ◽  
Similar Threshold ◽  
Receptive Field Center

Roughly half of all ganglion cells in mammalian retina belong to the broad class, termed “sluggish.” Many of these cells have small receptive fields and project via lateral geniculate nuclei to visual cortex. However, their possible contributions to perception have been largely ignored because sluggish cells seem to respond weakly compared with the more easily studied “brisk” cells. By selecting small somas under infrared DIC optics and recording with a loose seal, we could routinely isolate sluggish cells. When a spot was matched spatially and temporally to the receptive field center, most sluggish cells could detect the same low contrasts as brisk cells. Detection thresholds for the two groups determined by an “ideal observer” were similar: threshold contrast for sluggish cells was 4.7 ± 0.5% (mean ± SE), and for brisk cells was 3.4 ± 0.3% (Mann-Whitney test: P > 0.05). Signal-to-noise ratios for the two classes were also similar at low contrast. However, sluggish cells saturated at somewhat lower contrasts (contrast for half-maximum response was 14 ± 1 vs. 19 ± 2% for brisk cells) and were less sensitive to higher temporal frequencies (when the stimulus frequency was increased from 2 to 4 Hz, the response rate fell by 1.6-fold). Thus the sluggish cells covered a narrower dynamic range and a narrower temporal bandwidth, consistent with their reported lower information rates. Because information per spike is greater at lower firing rates, sluggish cells may represent “cheaper” channels that convey less urgent visual information at a lower energy cost.

scholarly journals A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies

2021 ◽  
Vol 14 (1) ◽  
pp. 50
Author(s):  
Alicia Arranz-Romera ◽  
Maria Hernandez ◽  
Patricia Checa-Casalengua ◽  
Alfredo Garcia-Layana ◽  
Irene T. Molina-Martinez ◽  
...  
Keyword(s):  
Cell Viability ◽  
Retinal Ganglion Cells ◽  
Neurotrophic Factor ◽  
Retinal Pigment Epithelial ◽  
Ganglion Cells ◽  
Retinal Pigment ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Retinal Ganglion ◽  
Pigment Epithelial

We assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.

scholarly journals PRESENCE OF A BASE LINE LEVEL OF SISTER CHROMATID EXCHANGES IN SOMATIC CELLS OF DROSOPHILA MELANOGASTER IN VIVO AND IN VITRO

Genetics ◽  
1982 ◽  
Vol 100 (2) ◽  
pp. 259-278
Author(s):  
Hideo Tsuji
Keyword(s):  
Drosophila Melanogaster ◽  
Sister Chromatid ◽  
Ganglion Cells ◽  
Sister Chromatid Exchanges ◽  
Base Line ◽  
Cell Cycles ◽  
Chromatid Exchanges ◽  
Third Instar Larvae

ABSTRACT Sister chromatid exchanges (SCEs) under in vivo and in vitro conditions were examined in ganglion cells of third-instar larvae of Drosophila melanogaster (Oregon-R). In the in vivo experiment, third-instar larvae were fed on synthetic media containing 5-bromo-2′-deoxyuridine (BrdUrd). After two cell cycles, ganglia were dissected and treated with colchicine. In the in vitro experiment, the ganglia were also incubated in media containing BrdUrd for two cell cycles, and treated with colchicine. SCEs were scored in metaphase stained with Hoechst 33258 plus Giemsa. The frequencies of SCEs stayed constant in the range of 25-150 vg/ml and 0.25-2.5 vg/ml of BrdUrd in vivo and in vitro, respectively. SCEs gradually increased at higher concentrations, strongly suggesting that at least a fraction of the detected SCEs are spontaneous. The constant levels of SCE frequency were estimated, on the average, at 0.103 per cell per two cell cycles for females and 0.101 for males in vivo and at 0.096 for females and 0.091 for males in vitro. No difference was found in the SCE frequency between sexes at any of the BrdUrd concentrations. The analysis for the distribution of SCEs within chromosomes revealed an extraordinarily high proportion of the SCEs at the junctions between euchromatin and heterochromatin; the remaining SCEs were preferentially localized in the euchromatic regions of the chromosomes and in the heterochromatic Y chromosome. These results were largely inconsistent with those of Gatti et al. (1979).

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

In vitro analysis of interactions between sensory neurons and skin: evidence for selective innervation of dermis and epidermis

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 53-70
Author(s):  
J.-M. Verna
Keyword(s):  
Ganglion Cells ◽  
Neurite Growth ◽  
Epidermal Cells ◽  
Serum Free Medium ◽  
Diffusible Factor ◽  
Vitro Analysis ◽  
Dermal Cells ◽  
Dorsal Root Ganglion Cells ◽  
In Vitro Analysis

Axons from dorsal root ganglion cells cultured in a serum-free medium on poly-L-lysine or collagen substrates interact differently with dermis and epidermis. The orientation of neurite growth is not changed by encountering mesenchymal cells migrating from the outgrowth zone of a dermal explant, and neurites form close membrane associations with some dermal cells; in contrast, neurites strongly avoid epidermis and deviate around the edge of an epidermal explant. When cultures are grown on polylysine this avoidance behaviour occurs at a distance from the epidermis. It is suppressed in the presence of necrotic epidermal cells. We suggest that this avoidance is due to epidermal diffusible factor(s) which bind preferentially to polylysine. The possibility of an absence of specific recognition cues between neurites and epidermal cells is discussed.

A coupled network for parasol but not midget ganglion cells in the primate retina

1992 ◽  
Vol 9 (3-4) ◽  
pp. 279-290 ◽  
Author(s):  
Dennis M. Dacey ◽  
Sarah Brace
Keyword(s):  
Nearest Neighbor ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Distinct Pattern ◽  
Field Size ◽  
Inner Plexiform Layer ◽  
Dendritic Field

AbstractIntracellular injections of Neurobiotin were used to determine whether the major ganglion cell classes of the macaque monkey retina, the magnocellular-projecting parasol, and the parvocellular-projecting midget cells showed evidence of cellular coupling similar to that recently described for cat retinal ganglion cells. Ganglion cells were labeled with the fluorescent dye acridine orange in an in vitro, isolated retina preparation and were selectively targeted for intracellular injection under direct microscopic control. The macaque midget cells, like the beta cells of the cat's retina, showed no evidence of tracer coupling when injected with Neurobiotin. By contrast, Neurobiotin-filled parasol cells, like cat alpha cells, showed a distinct pattern of tracer coupling to each other (homotypic coupling) and to amacrine cells (heterotypic coupling).In instances of homotypic coupling, the injected parasol cell was surrounded by a regular array of 3–6 neighboring parasol cells. The somata and proximal dendrites of these tracer-coupled cells were lightly labeled and appeared to costratify with the injected cell. Analysis of the nearest-neighbor distances for the parasol cell clusters showed that dendritic-field overlap remained constant as dendritic-field size increased from 100–400 μm in diameter.At least two amacrine cell types showed tracer coupling to parasol cells. One amacrine type had a small soma and thin, sparsely branching dendrites that extended for 1–2 mm in the inner plexiform layer. A second amacrine type had a relatively large soma, thick main dendrites, and distinct, axon-like processes that extended for at least 2–3 mm in the inner plexiform layer. The main dendrites of the large amacrine cells were closely apposed to the dendrites of parasol cells and may be the site of Neurobiotin transfer between the two cell types. We suggest that the tracer coupling between neighboring parasol cells takes place indirectly via the dendrites of the large amacrine cells and provides a mechanism, absent in midget cells, for increasing parasol cell receptive-field size and luminance contrast sensitivity.

Sign in / Sign up

Export Citation Format

Share Document