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 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 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.

A structural basis for omnidirectional connections between starburst amacrine cells and directionally selective ganglion cells in rabbit retina, with associated bipolar cells

2002 ◽  
Vol 19 (2) ◽  
pp. 145-162 ◽  
Author(s):  
E.V. FAMIGLIETTI
Keyword(s):  
Ganglion Cells ◽  
Dendritic Tree ◽  
Amacrine Cells ◽  
Dendritic Morphology ◽  
Bipolar Cells ◽  
Structural Basis ◽  
Rabbit Retina ◽  
Low Velocity ◽  
Accessory Optic System ◽  
Starburst Amacrine Cells

Directionally selective (DS) ganglion cells of rabbit retina are of two principal types. ON DS ganglion cells prefer low velocity in one of three directions of movement and project axons to the accessory optic system (AOS), whereas ON–OFF DS ganglion cells prefer higher velocity in one of four directions and project to tectum and thalamus. Each has a distinct, recognizable dendritic morphology, based upon the correlation of form, physiology, and central projections. In previous Golgi studies, ON and ON–OFF DS cells were found to be partly co-stratified, and ON–OFF DS cells were found to co-stratify with starburst amacrine (SA) cells, the cholinergic amacrine cells of the retina, which also contain elevated levels of GABA. SA cells are radially symmetrical, have synaptic boutons in a distal annular zone of its dendritic tree, are presynaptic primarily to ganglion cell dendrites, co-stratify with ON–OFF DS ganglion cells, and contain the neurotransmitters shown pharmacologically to be involved in DS responses. For these reasons, SA cells are thought to play a role in the DS mechanism. Several models of this mechanism have utilized SA cell dendritic geometry in a centrifugal, radial format to impose directional inputs on DS ganglion cells.

scholarly journals Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation

2019 ◽  
Vol 116 (8) ◽  
pp. 3262-3267 ◽  
Author(s):  
Yu-Tien Hsiao ◽  
Wen-Chi Shu ◽  
Pin-Chun Chen ◽  
Hui-Ju Yang ◽  
Hsin-Yo Chen ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Calcium Transients ◽  
Retinal Ganglion ◽  
Retinal Waves ◽  
Starburst Amacrine Cells ◽  
Retinogeniculate Projection ◽  
Wave Properties

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

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 Expression of a Barhl1a reporter in subsets of retinal ganglion cells and commissural neurons of the developing zebrafish brain

2020 ◽  
Author(s):  
Shahad Albadri ◽  
Olivier Armant ◽  
Tairi Aljand-Geschwill ◽  
Filippo Del Bene ◽  
Matthias Carl ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Optic Chiasm ◽  
Retinal Ganglion ◽  
Commissural Neurons ◽  
Axonal Projections ◽  
Underlying Mechanisms ◽  
And Function

AbstractPromoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, only barhl2 is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated the barhl1a and barhl2 paralogues. In the Zebrafish retina, Barhl2 functions as determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast, barhl1a expression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a:GFP reporter line in vivo showing that Barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of Barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.

Retinal ganglion cells projecting to the rabbit accessory optic system

1980 ◽  
Vol 190 (1) ◽  
pp. 49-61 ◽  
Author(s):  
Clyde W. Oyster ◽  
John I. Simpson ◽  
Ellen S. Takahashi ◽  
Robert E. Soodak
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Optic System ◽  
Accessory Optic System

scholarly journals Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Thomas A Ray ◽  
Suva Roy ◽  
Christopher Kozlowski ◽  
Jingjing Wang ◽  
Jon Cafaro ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Surface Protein ◽  
Amacrine Cells ◽  
Direction Selectivity ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Starburst Amacrine Cells ◽  
Developing Neurons

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers.

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