scholarly journals Synaptic circuits for irradiance coding by intrinsically photosensitive retinal ganglion cells

2018 ◽  
Author(s):  
Shai Sabbah ◽  
Carin Papendorp ◽  
Elizabeth Koplas ◽  
Marjo Beltoja ◽  
Cameron Etebari ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Electron Microscopic ◽  
Synaptic Circuits ◽  
Ribbon Synapses ◽  
High Pass ◽  
Excitatory Drive ◽  
Rod Bipolar Cells

SummaryWe have explored the synaptic networks responsible for the unique capacity of intrinsically photosensitive retinal ganglion cells (ipRGCs) to encode overall light intensity. This luminance signal is crucial for circadian, pupillary and related reflexive responses light. By combined glutamate-sensor imaging and patch recording of postsynaptic RGCs, we show that the capacity for intensity-encoding is widespread among cone bipolar types, including OFF types.Nonetheless, the bipolar cells that drive ipRGCs appear to carry the strongest luminance signal. By serial electron microscopic reconstruction, we show that Type 6 ON cone bipolar cells are the dominant source of such input, with more modest input from Types 7, 8 and 9 and virtually none from Types 5i, 5o, 5t or rod bipolar cells. In conventional RGCs, the excitatory drive from bipolar cells is high-pass temporally filtered more than it is in ipRGCs. Amacrine-to-bipolar cell feedback seems to contribute surprisingly little to this filtering, implicating mostly postsynaptic mechanisms. Most ipRGCs sample from all bipolar terminals costratifying with their dendrites, but M1 cells avoid all OFF bipolar input and accept only ectopic ribbon synapses from ON cone bipolar axonal shafts. These are remarkable monad synapses, equipped with as many as a dozen ribbons and only one postsynaptic process.

scholarly journals Activation of rod input in a model of retinal degeneration reverses retinal remodeling and induces formation of normal synapses, circuitry and visual signaling in the adult retina

2018 ◽  
Author(s):  
Tian Wang ◽  
Johan Pahlberg ◽  
Jon Cafaro ◽  
Alapakkam P. Sampath ◽  
Greg D. Field ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Retinal Ganglion Cells ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Rod Photoreceptors ◽  
Retinal Remodeling ◽  
Rod Bipolar Cells

AbstractA major cause of human blindness is the death of rod photoreceptors. As rods degenerate, synaptic structures between rod and rod bipolar cells dissolve and the rod bipolar cells extend their dendrites and occasionally make aberrant contacts. Such changes are broadly observed in blinding disorders caused by photoreceptor cell death and is thought to occur in response to deafferentation. How the remodeled retinal circuit affect visual processing following rod rescue is not known. To address this question, we generated transgenic mice wherein a disrupted cGMP-gated channel (CNG) gene can be repaired at the endogenous locus and at different stages of degeneration by tamoxifen-inducible cre-mediated recombination. In normal rods, light-induced closure of CNG channels leads to hyperpolarization of the cell, reducing neurotransmitter release at the synapse. Similarly, rods lacking CNG channel exhibit a resting membrane potential that was ~10mV hyperpolarized compared to WT rods, indicating diminished glutamate release. Retinas from these mice undergo stereotypic retinal remodeling as a consequence of rod malfunction and degeneration. Upon tamoxifen-induced expression of CNG channels, rods recovered their structure and exhibited normal light responses. Moreover, we show that the adult mouse retina displays a surprising degree of plasticity upon activation of rod input. Wayward bipolar cell dendrites establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings demonstrate remarkable plasticity extending beyond the developmental period and support efforts to repair or replace defective rods in patients blinded by rod degeneration.Significance StatementCurrent strategies for treatment of neurodegenerative disorders are focused on the repair of the primary affected cell type. However, the defective neuron functions within a complex neural circuitry, which also becomes degraded during disease. It is not known whether a rescued neuron and the remodeled circuit will establish communication to regain normal function. We show that the adult mammalian neural retina exhibits a surprising degree of plasticity following rescue of rod photoreceptors. The wayward rod bipolar cell dendrites re-establish contact with rods to support normal synaptic transmission, which is propagated to the retinal ganglion cells. These findings support efforts to repair or replace defective rods in patients blinded by rod cell loss.

scholarly journals Rod bipolar cells dysfunction occurs before ganglion cells loss in excitotoxin-damaged mouse retina

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Yumeng Shen ◽  
Xue Luo ◽  
Shiliang Liu ◽  
Ying Shen ◽  
Scott Nawy ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Experimental Models ◽  
Bipolar Cells ◽  
Diagnostic Tools ◽  
Mouse Retina ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Rod Bipolar Cells

AbstractProgressive degeneration of retinal ganglion cells (RGCs) will cause a blinding disease. Most of the study is focusing on the RGCs itself. In this study, we demonstrate a decline of the presynaptic rod bipolar cells (RBCs) response precedes RGCs loss and a decrease of protein kinase Cα (PKCα) protein expression in RBCs dendrites, using whole-cell voltage-clamp, electroretinography (ERG) measurements, immunostaining and co-immunoprecipitation. We present evidence showing that N-methyl D-aspartate receptor subtype 2B (NR2B)/protein interacting with C kinase 1 (PICK1)-dependent degradation of PKCα protein in RBCs contributes to RBCs functional loss. Mechanistically, NR2B forms a complex with PKCα and PICK1 to promote the degradation of PKCα in a phosphorylation- and proteasome-dependent manner. Similar deficits in PKCα expression and response sensitivity were observed in acute ocular hypertension and optic never crush models. In conclusion, we find that three separate experimental models of neurodegeneration, often used to specifically target RGCs, disrupt RBCs function prior to the loss of RGCs. Our findings provide useful information for developing new diagnostic tools and treatments for retinal ganglion cells degeneration disease.

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 Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

2017 ◽  
Vol 149 (3) ◽  
pp. 335-353 ◽  
Author(s):  
Xiwu Zhao ◽  
Aaron N. Reifler ◽  
Melanie M. Schroeder ◽  
Elizabeth R. Jaeckel ◽  
Andrew P. Chervenak ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Presynaptic Inhibition ◽  
Ganglion Cells ◽  
Glutamate Uptake ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
Light Responses ◽  
Comprehensive Survey ◽  
Underlying Mechanisms ◽  
Kinetics Of

Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs’ rod/cone-driven responses depends neither on melanopsin nor on N-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells’ responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca2+ as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or transient light responses. Parenthetically, we find evidence in both mice and rats that the kinetics of light-induced mGluR6 deactivation determines whether an ON bipolar cell responds tonically or transiently to light.

scholarly journals The expression and function of TRPV4 channels in primate retinal ganglion cells and bipolar cells

2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Fan Gao ◽  
Zhuo Yang ◽  
Roy A. Jacoby ◽  
Samuel M. Wu ◽  
Ji-Jie Pang
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Retinal Ganglion ◽  
And Function

scholarly journals T132. RETINAL GANGLION CELLS DYSFUNCTIONS IN SCHIZOPHRENIA PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S280-S281
Author(s):  
Florent Bernadin ◽  
Thomas Schwitzer ◽  
Vincent Laprevote ◽  
Raymund Schwan
Keyword(s):  
Retinal Ganglion Cells ◽  
Visual Processing ◽  
Wave Amplitude ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Implicit Time ◽  
Clinical Electrophysiology ◽  
Healthy Controls ◽  
Retinal Ganglion ◽  
Functional Responses

Abstract Background Structural and functional retinal anomalies are documented in neurologic, substance use and psychiatric disorders. In schizophrenia, flash electroretinogram (fERG) measures have revealed photoreceptors, bipolar cells and retinal ganglion cells (RGC) dysfunctions. To date, no study has explored RGC using a pattern electroretinogram (pERG) protocol as recommended by the International Society for Clinical Electrophysiology of Vision (ISCEV) standards for RGC measurements. We aim to study retinal functional responses of the photoreceptors and RGC in schizophrenia patients in comparison with healthy controls. Methods fERG conducted in scotopic (dark-adapted 0.01 and dark-adapted 3.0 ERG) and photopic conditions (light-adapted 3.0 ERG) and pERG were recorded in schizophrenia patients (n=29) and healthy controls (n=29). PERG provides the measurements of 2 waves: the P50 wave which arises in RGC with a contribution of bipolar cells and relates to the spatial distribution and density of the RGC bodies and the N95 wave which represents ganglion cell activity. Results fERG results showed a decrease in the b-wave amplitude (t(51)=-3.4, p<.05, d=0.63) (dark-adapted 0.01 ERG), a-wave amplitude (t(48)=4.7, p<.001, d =1.33) (dark-adapted 3.0 ERG), b-wave amplitude (t(48)=-2.8, p<.005, d=0.78) (dark-adapted 3.0 ERG), a-wave amplitude (t(52)=2.8, p<.001, d=0.29) (light-adapted 3.0 ERG) in schizophrenia patients compared to controls. We found as well a significant decrease of the a-wave implicit time (t(52)=-2.5, p<.05, d =1.19) (light-adapted 3.0 ERG) in schizophrenia patients compared to controls. pERG results showed a significant increase of the P50 (t(55)=2.1, p<.05, d=0.55) and a significant increase of the N95 implicit time in schizophrenia patients compared with controls (t(55)=4.2; p<.001, d=0.66). Discussion Our results replicate previous findings regarding photoreceptors and bipolar cells dysfunction in schizophrenia patients. pERG results demonstrate a delay in transmission of action potentials by the ganglion cells along the visual pathway via the optic nerve and the lateral geniculate nucleus to the visual cortex in schizophrenia patients which could support alterations in cerebral visual processing in schizophrenia.

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.

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