scholarly journals Retinal self-organization: a model of RGC and SAC mosaic formation

2021 ◽  
Author(s):  
Jean de Montigny ◽  
Evelyne Sernagor ◽  
Roman Bauer
Keyword(s):  
Visual Information ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Retinal Ganglion ◽  
Uniform Sampling ◽  
Tangential Migration ◽  
Starburst Amacrine Cells

Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. These mosaics enable uniform sampling of visual information and are formed to varying degrees across cell types. Retinal ganglion cells (RGC) and amacrine cells (including starburst amacrine cells (SAC)) are notably known to exhibit such layouts. Mechanisms responsible for the formation of such organised structures and their requirements are still not well understood. Mosaic formation follows three main principles: (1) homotypic cells prevent nearby cells from adopting the same type, (2) cell tangential migration, with homotypic cell repulsion, (3) cell death (with RGCs exhibiting high rates of apoptosis).

Development of cholinergic amacrine cell stratification in the ferret retina and the effects of early excitotoxic ablation

2001 ◽  
Vol 18 (4) ◽  
pp. 559-570 ◽  
Author(s):  
B.E. REESE ◽  
M.A. RAVEN ◽  
K.A. GIANNOTTI ◽  
P.T. JOHNSON
Keyword(s):  
Ganglion Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Outer Border ◽  
Cholinergic Amacrine Cells

The present study has examined the emergence of cholinergic stratification within the developing inner plexiform layer (IPL), and the effect of ablating the cholinergic amacrine cells on the formation of other stratifications within the IPL. The population of cholinergic amacrine cells in the ferret's retina was identified as early as the day of birth, but their processes did not form discrete strata until the end of the first postnatal week. As development proceeded over the next five postnatal weeks, so the positioning of the cholinergic strata shifted within the IPL toward the outer border, indicative of the greater ingrowth and elaboration of processes within the innermost parts of the IPL. To examine whether these cholinergic strata play an instructive role upon the development of other stratifications which form within the IPL, one-week-old ferrets were treated with l-glutamate in an attempt to ablate the population of cholinergic amacrine cells. Such treatment was shown to be successful, eliminating all of the cholinergic amacrine cells as well as the alpha retinal ganglion cells in the central retina. The remaining ganglion cell classes as well as a few other retinal cell types were partially reduced, while other cell types were not affected, and neither retinal histology nor areal growth was compromised in these ferrets. Despite this early loss of the cholinergic amacrine cells, which are eliminated within 24 h, other stratifications within the IPL formed normally, as they do following early elimination of the entire ganglion cell population. While these cholinergic amacrine cells are present well before other cell types have differentiated, apparently neither they, nor the ganglion cells, play a role in determining the depth of stratification for other retinal cell types.

scholarly journals GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

2018 ◽  
Vol 115 (51) ◽  
pp. E12083-E12090 ◽  
Author(s):  
Adam Bleckert ◽  
Chi Zhang ◽  
Maxwell H. Turner ◽  
David Koren ◽  
David M. Berson ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Selective Reduction ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Direction Selectivity ◽  
Inhibitory Synapses ◽  
Retinal Ganglion ◽  
Gabaergic Transmission ◽  
Starburst Amacrine Cells ◽  
Receptor Clusters

Synaptic inhibition controls a neuron’s output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on–off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC’s soma and dendrites could facilitate homeostatic control of the ooDSGC’s output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.

scholarly journals Axonal Sodium-Channel Bands Shape the Response to Electric Stimulation in Retinal Ganglion Cells

2009 ◽  
Vol 101 (4) ◽  
pp. 1972-1987 ◽  
Author(s):  
Shelley I. Fried ◽  
Aaron C. W. Lasker ◽  
Neal J. Desai ◽  
Donald K. Eddington ◽  
Joseph F. Rizzo
Keyword(s):  
Sodium Channel ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Electric Stimulation ◽  
Ganglion Cells ◽  
Cell Types ◽  
Threshold Region ◽  
Retinal Ganglion ◽  
Neural Prosthetic ◽  
Voltage Gated Sodium Channels

Electric stimulation of the retina reliably elicits light percepts in patients blinded by outer retinal diseases. However, individual percepts are highly variable and do not readily assemble into more complex visual images. As a result, the quality of visual information conveyed to patients has been quite limited. To develop more effective stimulation methods that will lead to improved psychophysical outcomes, we are studying how retinal neurons respond to electric stimulation. The situation in the retina is analogous to other neural prosthetic applications in which a better understanding of the underlying neural response may lead to improved clinical outcomes. Here, we determined which element in retinal ganglion cells has the lowest threshold for initiating action potentials. Previous studies suggest multiple possibilities, although all were within the soma/proximal axon region. To determine the actual site, we measured thresholds in a dense two-dimensional grid around the soma/proximal axon region of rabbit ganglion cells in the flat mount preparation. In directionally selective (DS) ganglion cells, the lowest thresholds were found along a small section of the axon, about 40 μm from the soma. Immunochemical staining revealed a dense band of voltage-gated sodium channels centered at the same location, suggesting that thresholds are lowest when the stimulating electrode is closest to the sodium-channel band. The size and location of the low-threshold region was consistent within DS cells, but varied for other ganglion cell types. Analogously, the length and location of sodium channel bands also varied by cell type. Consistent with the differences in band properties, we found that the absolute (lowest) thresholds were also different for different cell types. Taken together, our results suggest that the sodium-channel band is the site that is most responsive to electric stimulation and that differences in the bands underlie the threshold differences we observed.

scholarly journals An alternative approach to produce versatile retinal organoids with accelerated ganglion cell development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philip E. Wagstaff ◽  
Anneloor L. M. A. ten Asbroek ◽  
Jacoline B. ten Brink ◽  
Nomdo M. Jansonius ◽  
Arthur A. B. Bergen
Keyword(s):  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Cell ◽  
Specific Cell ◽  
Retinal Ganglion ◽  
In Vivo Models ◽  
Alternative Approach

AbstractGenetically complex ocular neuropathies, such as glaucoma, are a major cause of visual impairment worldwide. There is a growing need to generate suitable human representative in vitro and in vivo models, as there is no effective treatment available once damage has occured. Retinal organoids are increasingly being used for experimental gene therapy, stem cell replacement therapy and small molecule therapy. There are multiple protocols for the development of retinal organoids available, however, one potential drawback of the current methods is that the organoids can take between 6 weeks and 12 months on average to develop and mature, depending on the specific cell type wanted. Here, we describe and characterise a protocol focused on the generation of retinal ganglion cells within an accelerated four week timeframe without any external small molecules or growth factors. Subsequent long term cultures yield fully differentiated organoids displaying all major retinal cell types. RPE, Horizontal, Amacrine and Photoreceptors cells were generated using external factors to maintain lamination.

scholarly journals Differential expression of PKCα and -β in the zebrafish retina

2018 ◽  
Author(s):  
Marion F. Haug ◽  
Manuela Berger ◽  
Matthias Gesemann ◽  
Stephan C. F. Neuhauss
Keyword(s):  
Bipolar Cell ◽  
Visual Information ◽  
Neural Circuit ◽  
Ganglion Cells ◽  
Immunohistochemical Analysis ◽  
Cell Types ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Retinal Tissue ◽  
Kinase C

AbstractThe retina is a complex neural circuit in which visual information is transmitted and processed from light perceiving photoreceptors to projecting retinal ganglion cells. Much of the computational power of the retina rests on signal integrating interneurons, such as bipolar cells in the outer retina. While mammals possess about 10 different bipolar cell types, zebrafish (Danio rerio) has at least six ON-type, seven OFF-type, and four mixed-input bipolar cells. Commercially available antibodies against bovine and human conventional protein kinase C (PKC) α and -β are frequently used as markers for retinal ON-bipolar cells in different species, despite the fact that it is not known which bipolar cell subtype(s) they actually label.Moreover, the expression pattern of the five prkc genes (coding for PKC proteins) has not been systematically determined. While prkcg is not expressed in retinal tissue, the other four prkc (prkcaa, prkcab, prkcba, prkcbb) transcripts were found in different parts of the inner nuclear layer and some as well in the retinal ganglion cell layer.Immunohistochemical analysis in adult zebrafish retina using PKCα and PKCβ antibodies showed an overlapping immunolabeling of ON-bipolar cells that are most likely of the BON s6L or RRod type and of the BON s6 type. However, comparison of transcript expression with immunolabling, implies that these antibodies are not specific for one single zebrafish conventional PKC, but rather detect a combination of PKC -α and -β variants.

scholarly journals Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells

2021 ◽  
Vol 15 ◽  
Author(s):  
Elena G. Sergeeva ◽  
Paul A. Rosenberg ◽  
Larry I. Benowitz
Keyword(s):  
Optic Nerve ◽  
Visual Information ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Inflammatory Cells ◽  
Retinal Ganglion ◽  
Ability To Regenerate ◽  
Mature Neurons ◽  
The Central Nervous System ◽  
Extracellular Environment

Visual information is conveyed from the eye to the brain through the axons of retinal ganglion cells (RGCs) that course through the optic nerve and synapse onto neurons in multiple subcortical visual relay areas. RGCs cannot regenerate their axons once they are damaged, similar to most mature neurons in the central nervous system (CNS), and soon undergo cell death. These phenomena of neurodegeneration and regenerative failure are widely viewed as being determined by cell-intrinsic mechanisms within RGCs or to be influenced by the extracellular environment, including glial or inflammatory cells. However, a new concept is emerging that the death or survival of RGCs and their ability to regenerate axons are also influenced by the complex circuitry of the retina and that the activation of a multicellular signaling cascade involving changes in inhibitory interneurons – the amacrine cells (AC) – contributes to the fate of RGCs. Here, we review our current understanding of the role that interneurons play in cell survival and axon regeneration after optic nerve injury.

scholarly journals FLRT3 Marks Direction-Selective Retinal Ganglion Cells That Project to the Medial Terminal Nucleus

2021 ◽  
Vol 14 ◽  
Author(s):  
Tobias Ruff ◽  
Christian Peters ◽  
Akihiro Matsumoto ◽  
Stephan J. Ihle ◽  
Pilar Alcalá Morales ◽  
...  
Keyword(s):  
Fluorescent Dyes ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Functional Characterization ◽  
Amacrine Cells ◽  
Color Contrast ◽  
Retinal Ganglion ◽  
Accessory Optic System ◽  
Starburst Amacrine Cells ◽  
Medial Terminal Nucleus

The mammalian retina extracts a multitude of diverse features from the visual scene such as color, contrast, and direction of motion. These features are transmitted separately to the brain by more than 40 different retinal ganglion cell (RGC) subtypes. However, so far only a few genetic markers exist to fully characterize the different RGC subtypes. Here, we present a novel genetic Flrt3-CreERT2 knock-in mouse that labels a small subpopulation of RGCs. Using single-cell injection of fluorescent dyes in Flrt3 positive RGCs, we distinguished four morphological RGC subtypes. Anterograde tracings using a fluorescent Cre-dependent Adeno-associated virus (AAV) revealed that a subgroup of Flrt3 positive RGCs specifically project to the medial terminal nucleus (MTN), which is part of the accessory optic system (AOS) and is essential in driving reflex eye movements for retinal image stabilization. Functional characterization using ex vivo patch-clamp recordings showed that the MTN-projecting Flrt3 RGCs preferentially respond to downward motion in an ON-fashion. These neurons distribute in a regular pattern and most of them are bistratified at the level of the ON and OFF bands of cholinergic starburst amacrine cells where they express the known ON-OFF direction-selective RGC marker CART. Together, our results indicate that MTN-projecting Flrt3 RGCs represent a new functionally homogeneous AOS projecting direction-selective RGC subpopulation.

scholarly journals Evidence for novel transient clusters of cholinergic ganglion cells in the neonatal mouse retina

2019 ◽  
Author(s):  
Jean de Montigny ◽  
Vidhyasankar Krishnamoorthy ◽  
Fernando Rozenblit ◽  
Tim Gollisch ◽  
Evelyne Sernagor
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Neonatal Mouse ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Electrical Imaging ◽  
Subplate Neurons ◽  
Starburst Amacrine Cells ◽  
Cholinergic Cell

AbstractWaves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) layer, driven by directly interconnected cholinergic starburst amacrine cells (the only known retinal cholinergic cells) from postnatal day (P) 0-10, followed by waves driven by glutamatergic bipolar cells. We found transient clusters of cholinergic RGC-like cells around the optic disc during the period of cholinergic waves. They migrate towards the periphery between P2-9 and then they disappear. Pan-retinal multielectrode array recordings reveal that cholinergic wave origins follow a similar developmental center-to-periphery pattern. Electrical imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. We propose that these activity hotspots are sites for wave initiation and are related to the cholinergic cell clusters, reminiscent of activity in transient subplate neurons in the developing cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks during the critical period for brain wiring.

Catecholamine-, Indoleamine-, and GABA-containing cells in the chameleon retina

1995 ◽  
Vol 12 (4) ◽  
pp. 785-792 ◽  
Author(s):  
Mohamed Bennis ◽  
Claudine Versaux-Botteri
Keyword(s):  
Tyrosine Hydroxylase ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Cell Types ◽  
Aminobutyric Acid ◽  
Retinal Cell ◽  
Gamma Aminobutyric Acid ◽  
First Report ◽  
Soma Size ◽  
Displaced Amacrine Cells

AbstractNeurons containing catecholamine, indoleamine, and gamma-aminobutyric acid (GABA) were identified by immunohistochemistry in the chameleon retina. Tyrosine hydroxylase (TH) and serotonin (5HT) were observed mostly in two subtypes of orthotopic amacrine cells differing in their soma size and process distribution within the IPL. Some labelled cells were displaced either to the IPL (5HT) or to the GCL (TH and 5HT). A multiplicity of retinal cell types contained GABA including cones, horizontal, amacrine, and ganglion cells. Our results confirmed those obtained in the retinas of other lizards except for the presence of interstitial and displaced amacrine cells containing TH or 5HT of which this is the first report.

scholarly journals Molecular classification of zebrafish retinal ganglion cells links genes to cell types to behavior

2020 ◽  
Author(s):  
Yvonne Kölsch ◽  
Joshua Hahn ◽  
Anna Sappington ◽  
Manuel Stemmer ◽  
António M. Fernandes ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Ganglion Cells ◽  
Molecular Classification ◽  
Cell Types ◽  
Brain Regions ◽  
Marker Genes ◽  
Small Subset ◽  
Retinal Ganglion

SummaryRetinal ganglion cells (RGCs) form an array of feature detectors, which convey visual information to central brain regions. Characterizing RGC diversity is required to understand the logic of the underlying functional segregation. Using single-cell transcriptomics, we systematically classified RGCs in adult and larval zebrafish, thereby identifying marker genes for at least 33 stable and transient cell types. We used this dataset to engineer transgenic driver lines, enabling experimental access to specific RGC types. Strikingly, expression of one or few transcription factors often predicts dendrite morphologies and axonal projections to specific tectal layers and extratectal targets. In vivo calcium imaging revealed that molecularly defined RGCs exhibit highly specific functional tuning. Finally, chemogenetic ablation of eomesa+ RGCs, which comprise melanopsin-expressing types with projections to a small subset of central targets, selectively impaired phototaxis. Together, our study establishes a framework for systematically studying the functional architecture of the visual system.

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