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 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 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 Short-wavelength cone-opponent retinal ganglion cells in mammals

2014 ◽  
Vol 31 (2) ◽  
pp. 165-175 ◽  
Author(s):  
DAVID W. MARSHAK ◽  
STEPHEN L. MILLS
Keyword(s):  
Retinal Ganglion Cells ◽  
Short Wavelength ◽  
Ganglion Cells ◽  
Mammalian Species ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Opposite Polarity ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Cone Bipolar Cells

AbstractIn all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

Interactions of Inhibition and Excitation in the Light-Evoked Currents of X Type Retinal Ganglion Cells

1998 ◽  
Vol 80 (6) ◽  
pp. 2975-2990 ◽  
Author(s):  
Ethan D. Cohen
Keyword(s):  
Retinal Ganglion Cells ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Cell Function ◽  
Ganglion Cells ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Retinal Ganglion ◽  
Inhibitory Conductance ◽  
X Cells

Cohen, Ethan D. Interactions of inhibition and excitation in the light-evoked currents of X type retinal ganglion cells. J. Neurophysiol. 80: 2975–2990, 1998. The excitatory and inhibitory conductances driving the light-evoked currents (LECs) of cat and ferret on- and off-center X ganglion cells were examined in sliced and isolated retina preparations using center spot stimulation in tetrodotoxin (TTX)-containing Ringer. on-center X ganglion cells showed an increase in an excitatory conductance reversed positive to +20 mV during the spot stimulus. At spot offset, a transient inhibitory conductance was activated on many cells that reversed near E Cl. off-center X ganglion cells showed increases in a sustained inhibitory conductance that reversed near E Cl during spot stimulation. At spot offset, an excitatory conductance was activated that reversed positive to +20 mV. The light-evoked current kinetics of on- and off-center X cells to spot stimulation did not significantly differ in form from their Y cell counterparts in TTX Ringer. When inhibition was blocked, current-voltage relations of the light-evoked excitatory postsynaptic currents (EPSCs) of both on- and off-X cells were L-shaped and reversed near 0 mV. The EPSCs averaged between 300 and 500 pA at −80 mV. The metabotropic glutamate receptor agonist 2-amino-4-phosphonobutyric acid (APB), was used to block on-center bipolar cell function. The LECs of on-X ganglion cells were totally blocked in APB at all holding potentials. APB caused prominent reductions in the dark holding current and synaptic noise of on-X cells. In contrast, the LECs of off-X ganglion cells remained in APB. An increase in the dark holding current was observed. The excitatory amino acid receptor antagonist combination of d-amino-5-phosphono-pentanoic acid (d-AP5) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)-quinoxalinedione (NBQX) was used to block ionotropic glutamate receptor retinal neurotransmission. The LECs of all on-X ganglion cells were totally blocked, and their holding currents were reduced similar to the actions of APB. For off-X ganglion cells, the antagonist combination always blocked the excitatory current at light-off; however, in many cells, the inhibitory current at light-on remained. on-center X ganglion cells receive active excitation during center illumination, and a transient inhibition at light-off. In contrast off-center X ganglion cells experience a sustained active inhibition during center illumination, and a shorter increase in excitation at light-offset. Cone bipolar cells provide a resting level of glutamate release on X ganglion cells on which their light-evoked currents are superimposed.

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.

Characterization of Spontaneous Inhibitory Synaptic Currents in Salamander Retinal Ganglion Cells

1998 ◽  
Vol 80 (4) ◽  
pp. 1752-1764 ◽  
Author(s):  
Fan Gao ◽  
Samuel M. Wu
Keyword(s):  
Retinal Ganglion Cells ◽  
Synaptic Vesicles ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Equilibrium Potential ◽  
Retinal Ganglion ◽  
Light Onset ◽  
Synaptic Currents ◽  
Postsynaptic Currents

Gao, Fan and Samuel M. Wu. Characterization of spontaneous inhibitory synaptic currents in salamander retinal ganglion cells. J. Neurophysiol. 80: 1752–1764, 1998. Spontaneous and light-evoked postsynaptic currents (sPSCs and lePSCs, respectively) in retinal ganglion cells of the larval tiger salamander were recorded under voltage-clamp conditions from living retinal slices. The focus of this study is to characterize the spontaneous inhibitory PSCs (sIPSCs) and their contribution to the light-evoked inhibitory PSCs (leIPSCs) in on-off ganglion cells. sIPSCs were isolated from spontaneous excitatory PSCs (sEPSCs) by application of 10 μM 6,7-dinitroquinoxaline-2,3-dione (DNQX) + 50 μM 2-amino-5-phosphonopentanoic acid (AP5). In ∼70% of on-off ganglion cells, bicuculline (or picrotoxin) completely blocks sIPSCs, suggesting all sIPSCs in these cells are mediated by GABAergic synaptic vesicles and γ-aminobutyric acid-A (GABAA) receptors (GABAergic sIPSCs, or GABAsIPSCs). In the remaining 30% of on-off ganglion cells, bicuculline (or picrotoxin) blocks 70–98% of the sIPSCs, and the remaining 2–30% are blocked by strychnine (glycinergic sIPSCs, or GLYsIPSCs). GABAsIPSCs occur randomly with an exponentially distributed interval probability density function, and they persist without noticeable rundown over time. The GABAsIPSC frequency is greatly reduced by cobalt, consistent with the idea that they are largely mediated by calcium-dependent vesicular release. GABAsIPSCs in DNQX + AP5 are tetrodotoxin (TTX) insensitive, suggesting that amacrine cells that release GABA under these conditions do not generate spontaneous action potentials. The average GABAsIPSCs exhibited linear current-voltage relation with a reversal potential near the chloride equilibrium potential, and an average peak conductance of 319.67 ± 252.83 (SD) pS. For GLYsIPSCs, the average peak conductance increase is 301.68 ± 94.34 pS. These parameters are of the same order of magnitude as those measured in inhibitory miniature postsynaptic currents (mIPSCs) associated with single synaptic vesicles in the CNS. The amplitude histograms of GABAsIPSCs did not exhibit multiple peaks, suggesting that the larger events are not discrete multiples of elementary events (or quanta). We propose that each GABAsIPSC or GLYsIPSC in retinal ganglion cells is mediated by a single or synchronized multiple of synaptic vesicles with variable neurotransmitter contents. In a sample of 16 on-off ganglion cells, the average peak leIPSC (held at 0 mV) at the light onset is 509.0 ± 233.85 pA and that at the light offset is 529.0 ± 339.88 pA. The approximate number of GABAsIPSCs and GLYsIPSCs required to generate the average light responses, calculated by the ratio of the charge (area under current traces) of the leIPSCs to that of the average single sIPSCs, is 118 ± 52 for the light onset, and 132 ± 76 for the light offset.

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.

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