scholarly journals Synaptic pathways that shape the excitatory drive in an OFF retinal ganglion cell

2012 ◽  
Vol 107 (7) ◽  
pp. 1795-1807 ◽  
Author(s):  
Ilya Buldyrev ◽  
Theresa Puthussery ◽  
W. Rowland Taylor
Keyword(s):  
Ampa Receptors ◽  
Ganglion Cells ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Excitatory Input ◽  
Disodium Salt ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Inhibitory Mechanisms ◽  
Spatiotemporal Filters

Different types of retinal ganglion cells represent distinct spatiotemporal filters that respond selectively to specific features in the visual input. Much about the circuitry and synaptic mechanisms that underlie such specificity remains to be determined. This study examines how N-methyl-d-aspartate (NMDA) receptor signaling combines with other excitatory and inhibitory mechanisms to shape the output of small-field OFF brisk-sustained ganglion cells (OFF-BSGCs) in the rabbit retina. We used voltage clamp to separately resolve NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and inhibitory inputs elicited by stimulation of the receptive field center. Three converging circuits were identified. First is a direct glutamatergic input, arising from OFF cone bipolar cells (CBCs), which is mediated by synaptic NMDA and AMPA receptors. The NMDA input was saturated at 10% contrast, whereas the AMPA input increased monotonically up to 60% contrast. We propose that NMDA inputs selectively enhance sensitivity to low contrasts. The OFF bipolar cells, mediating this direct excitatory input, express dendritic kainate (KA) receptors, which are resistant to the nonselective AMPA/KA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX), but are suppressed by a GluK1- and GluK3-selective antagonist, ( S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-thiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione (UBP-310). The second circuit entails glycinergic crossover inhibition, arising from ON-CBCs and mediated by AII amacrine cells, which modulate glutamate release from the OFF-CBC terminals. The third circuit also comprises glycinergic crossover inhibition, which is driven by the ON pathway; however, this inhibition impinges directly on the OFF-BSGCs and is mediated by an unknown glycinergic amacrine cell that expresses AMPA but not KA receptors.

Functional Circuitry for Peripheral Suppression in Mammalian Y-Type Retinal Ganglion Cells

2007 ◽  
Vol 97 (6) ◽  
pp. 4327-4340 ◽  
Author(s):  
Kareem A. Zaghloul ◽  
Michael B. Manookin ◽  
Bart G. Borghuis ◽  
Kwabena Boahen ◽  
Jonathan B. Demb
Keyword(s):  
Receptive Field ◽  
Ganglion Cell ◽  
Voltage Clamp ◽  
Ganglion Cells ◽  
Glutamate Release ◽  
High Spatial Frequency ◽  
Amacrine Cells ◽  
Horizontal Cells ◽  
Retinal Ganglion

A retinal ganglion cell receptive field is made up of an excitatory center and an inhibitory surround. The surround has two components: one driven by horizontal cells at the first synaptic layer and one driven by amacrine cells at the second synaptic layer. Here we characterized how amacrine cells inhibit the center response of on- and off-center Y-type ganglion cells in the in vitro guinea pig retina. A high spatial frequency grating (4–5 cyc/mm), beyond the spatial resolution of horizontal cells, drifted in the ganglion cell receptive field periphery to stimulate amacrine cells. The peripheral grating suppressed the ganglion cell spiking response to a central spot. Suppression of spiking was strongest and observed most consistently in off cells. In intracellular recordings, the grating suppressed the subthreshold membrane potential in two ways: a reduced slope (gain) of the stimulus-response curve by ∼20–30% and, in off cells, a tonic ∼1-mV hyperpolarization. In voltage clamp, the grating increased an inhibitory conductance in all cells and simultaneously decreased an excitatory conductance in off cells. To determine whether center response inhibition was presynaptic or postsynaptic (shunting), we measured center response gain under voltage-clamp and current-clamp conditions. Under both conditions, the peripheral grating reduced center response gain similarly. This result suggests that reduced gain in the ganglion cell subthreshold center response reflects inhibition of presynaptic bipolar terminals. Thus amacrine cells suppressed ganglion cell center response gain primarily by inhibiting bipolar cell glutamate release.

scholarly journals Synaptic inputs from identified bipolar and amacrine cells to a sparsely branched ganglion cell in rabbit retina

2019 ◽  
Vol 36 ◽  
Author(s):  
Andrea S. Bordt ◽  
Diego Perez ◽  
Luke Tseng ◽  
Weiley Sunny Liu ◽  
Jay Neitz ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Rabbit Retina ◽  
Retinal Ganglion ◽  
Synaptic Inputs ◽  
Class Iv

AbstractThere are more than 30 distinct types of mammalian retinal ganglion cells, each sensitive to different features of the visual environment. In rabbit retina, they can be grouped into four classes according to their morphology and stratification of their dendrites in the inner plexiform layer (IPL). The goal of this study was to describe the synaptic inputs to one type of Class IV ganglion cell, the third member of the sparsely branched Class IV cells (SB3). One cell of this type was partially reconstructed in a retinal connectome developed using automated transmission electron microscopy (ATEM). It had slender, relatively straight dendrites that ramify in the sublamina a of the IPL. The dendrites of the SB3 cell were always postsynaptic in the IPL, supporting its identity as a ganglion cell. It received 29% of its input from bipolar cells, a value in the middle of the range for rabbit retinal ganglion cells studied previously. The SB3 cell typically received only one synapse per bipolar cell from multiple types of presumed OFF bipolar cells; reciprocal synapses from amacrine cells at the dyad synapses were infrequent. In a few instances, the bipolar cells presynaptic to the SB3 ganglion cell also provided input to an amacrine cell presynaptic to the ganglion cell. There was apparently no crossover inhibition from narrow-field ON amacrine cells. Most of the amacrine cell inputs were from axons and dendrites of GABAergic amacrine cells, likely providing inhibitory input from outside the classical receptive field.

scholarly journals The effects of early diabetes on inner retinal neurons

2020 ◽  
Vol 37 ◽  
Author(s):  
Erika D. Eggers ◽  
Teresia A. Carreon
Keyword(s):  
Ganglion Cells ◽  
Early Stage ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Gaba Release ◽  
Bipolar Cells ◽  
Gamma Aminobutyric Acid ◽  
Early Diabetes

Abstract Diabetic retinopathy is now well understood as a neurovascular disease. Significant deficits early in diabetes are found in the inner retina that consists of bipolar cells that receive inputs from rod and cone photoreceptors, ganglion cells that receive inputs from bipolar cells, and amacrine cells that modulate these connections. These functional deficits can be measured in vivo in diabetic humans and animal models using the electroretinogram (ERG) and behavioral visual testing. Early effects of diabetes on both the human and animal model ERGs are changes to the oscillatory potentials that suggest dysfunctional communication between amacrine cells and bipolar cells as well as ERG measures that suggest ganglion cell dysfunction. These are coupled with changes in contrast sensitivity that suggest inner retinal changes. Mechanistic in vitro neuronal studies have suggested that these inner retinal changes are due to decreased inhibition in the retina, potentially due to decreased gamma aminobutyric acid (GABA) release, increased glutamate release, and increased excitation of retinal ganglion cells. Inner retinal deficits in dopamine levels have also been observed that can be reversed to limit inner retinal damage. Inner retinal targets present a promising new avenue for therapies for early-stage diabetic eye disease.

Amacrine and bipolar inputs to midget and parasol ganglion cells in marmoset retina

2012 ◽  
Vol 29 (3) ◽  
pp. 157-168 ◽  
Author(s):  
CARLA J. ABBOTT ◽  
KUMIKO A. PERCIVAL ◽  
PAUL R. MARTIN ◽  
ULRIKE GRÜNERT
Keyword(s):  
Visual Angle ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Average Density ◽  
Bipolar Cells ◽  
Inhibitory Synapses ◽  
Peripheral Retina ◽  
Excitatory Synapses ◽  
Retinal Ganglion ◽  
Retrograde Filling

AbstractRetinal ganglion cells receive excitatory synapses from bipolar cells and inhibitory synapses from amacrine cells. Previous studies in primate suggest that the strength of inhibitory amacrine input is greater to cells in peripheral retina than to foveal (central) cells. A comprehensive study of a large number of ganglion cells at different eccentricities, however, is still lacking. Here, we compared the amacrine and bipolar input to midget and parasol ganglion cells in central and peripheral retina of marmosets (Callithrix jacchus). Ganglion cells were labeled by retrograde filling from the lateral geniculate nucleus or by intracellular injection. Presumed amacrine input was identified with antibodies against gephyrin; presumed bipolar input was identified with antibodies against the GluR4 subunit of the AMPA receptor. In vertical sections, about 40% of gephyrin immunoreactive (IR) puncta were colocalized with GABAA receptor subunits, whereas immunoreactivity for gephyrin and GluR4 was found at distinct sets of puncta. The density of gephyrin IR puncta associated with ganglion cell dendrites was comparable for midget and parasol cells at all eccentricities studied (up to 2 mm or about 16 degrees of visual angle for midget cells and up to 10 mm or >80 degrees of visual angle for parasol cells). In central retina, the densities of gephyrin IR and GluR4 IR puncta associated with the dendrites of midget and parasol cells are comparable, but the average density of GluR4 IR puncta decreased slightly in peripheral parasol cells. These anatomical results indicate that the ratio of amacrine to bipolar input does not account for the distinct functional properties of parasol and midget cells or for functional differences between cells of the same type in central and peripheral retina.

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.

scholarly journals The nonlinear pathway of Y ganglion cells in the cat retina.

1979 ◽  
Vol 74 (6) ◽  
pp. 671-689 ◽  
Author(s):  
J D Victor ◽  
R M Shapley
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Second Order ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Linear Filters ◽  
Nonlinear Responses ◽  
Cat Retina ◽  
Different Types ◽  
Y Cells

Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a "sandwich model" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells.

scholarly journals Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Haruki Takeuchi ◽  
Sho Horie ◽  
Satoru Moritoh ◽  
Hiroki Matsushima ◽  
Tesshu Hori ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Transient Receptor Potential ◽  
Metabotropic Glutamate Receptor ◽  
Ganglion Cells ◽  
Receptor Potential ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Essential Components ◽  
Spontaneous Oscillations

TRPM1, the first member of the melanoma-related transient receptor potential (TRPM) subfamily, is the visual transduction channel downstream of metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells (BCs). Human TRPM1 mutations are associated with congenital stationary night blindness (CSNB). In both TRPM1 and mGluR6 KO mouse retinas, OFF but not ON BCs respond to light stimulation. Here we report an unexpected difference between TRPM1 knockout (KO) and mGluR6 KO mouse retinas. We used a multielectrode array (MEA) to record spiking in retinal ganglion cells (RGCs). We found spontaneous oscillations in TRPM1 KO retinas, but not in mGluR6 KO retinas. We performed a structural analysis on the synaptic terminals of rod ON BCs. Intriguingly, rod ON BC terminals were significantly smaller in TRPM1 KO retinas than in mGluR6 KO retinas. These data suggest that a deficiency of TRPM1, but not of mGluR6, in rod ON bipolar cells may affect synaptic terminal maturation. We speculate that impaired signaling between rod BCs and AII amacrine cells (ACs) leads to spontaneous oscillations. TRPM1 and mGluR6 are both essential components in the signaling pathway from photoreceptors to ON BC dendrites, yet they differ in their effects on the BC terminal and postsynaptic circuitry.

scholarly journals N-type and L-type calcium channels mediate glycinergic synaptic inputs to retinal ganglion cells of tiger salamanders

2004 ◽  
Vol 21 (4) ◽  
pp. 545-550 ◽  
Author(s):  
MARK C. BIEDA ◽  
DAVID R. COPENHAGEN
Keyword(s):  
Calcium Channels ◽  
Retinal Ganglion Cells ◽  
Channel Blocker ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Tiger Salamanders ◽  
Synaptic Release ◽  
Glycine Release

Synaptically localized calcium channels shape the timecourse of synaptic release, are a prominent site for neuromodulation, and have been implicated in genetic disease. In retina, it is well established that L-type calcium channels play a major role in mediating release of glutamate from the photoreceptors and bipolar cells. However, little is known about which calcium channels are coupled to synaptic exocytosis of glycine, which is primarily released by amacrine cells. A recent report indicates that glycine release from spiking AII amacrine cells relies exclusively upon L-type calcium channels. To identify calcium channel types controlling neurotransmitter release from the population of glycinergic neurons that drive retinal ganglion cells, we recorded electrical and potassium evoked inhibitory synaptic currents (IPSCs) from these postsynaptic neurons in retinal slices from tiger salamanders. The L-channel antagonist nifedipine strongly inhibited release and FPL64176, an L-channel agonist, greatly enhanced it, indicating a significant role for L-channels. ω-Conotoxin MVIIC, an N/P/Q-channel antagonist, strongly inhibited release, indicating an important role for non-L channels. While the P/Q-channel blocker ω-Aga IVA produced only small effects, the N-channel blocker ω-conotoxin GVIA strongly inhibited release. Hence, N-type and L-type calcium channels appear to play major roles, overall, in mediating synaptic release of glycine onto retinal ganglion cells.

scholarly journals Destructive Effect of Intravitreal Heat Shock Protein 27 Application on Retinal Ganglion Cells and Neurofilament

2020 ◽  
Vol 21 (2) ◽  
pp. 549 ◽  
Author(s):  
Pia Grotegut ◽  
Sandra Kuehn ◽  
H. Burkhard Dick ◽  
Stephanie C. Joachim
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Heat Shock Protein 27 ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Destructive Effect ◽  
And Control

Heat shock protein 27 (HSP27) is commonly involved in cellular stress. Increased levels of HSP27 as well as autoantibodies against this protein were previously detected in glaucoma patients. Moreover, systemic immunization with HSP27 induced glaucoma-like damage in rodents. Now, for the first time, the direct effects of an intravitreal HSP27 application were investigated. For this reason, HSP27 or phosphate buffered saline (PBS, controls) was applied intravitreally in rats (n = 12/group). The intraocular pressure (IOP) as well as the electroretinogram recordings were comparable in HSP27 and control eyes 21 days after the injection. However, significantly fewer retinal ganglion cells (RGCs) and amacrine cells were observed in the HSP27 group via immunohistochemistry and western blot analysis. The number of bipolar cells, on the other hand, was similar in both groups. Interestingly, a stronger neurofilament degeneration was observed in HSP27 optic nerves, while no differences were noted regarding the myelination state. In summary, intravitreal HSP27 injection led to an IOP-independent glaucoma-like damage. A degeneration of RGCs as well as their axons and amacrine cells was noted. This suggests that high levels of extracellular HSP27 could have a direct damaging effect on RGCs.

scholarly journals RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells

2015 ◽  
Vol 26 (20) ◽  
pp. 3671-3678 ◽  
Author(s):  
Marquis T. Walker ◽  
Alan Rupp ◽  
Rebecca Elsaesser ◽  
Ali D. Güler ◽  
Wenlong Sheng ◽  
...  
Keyword(s):  
Ganglion Cells ◽  
Light Response ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Light Conditions ◽  
Light Responses ◽  
Pupillary Light ◽  
Dim Light ◽  
Light Input

A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2− /− mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2− /− were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2− /− mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light.

Sign in / Sign up

Export Citation Format

Share Document