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 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.

Synaptic inputs to physiologically defined turtle retinal ganglion cells

1991 ◽  
Vol 7 (5) ◽  
pp. 409-429 ◽  
Author(s):  
Jay F. Muller ◽  
Josef Ammermüller ◽  
Richard A. Normann ◽  
Helga Kolb
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Bipolar Cell ◽  
Ganglion Cells ◽  
Bipolar Cells ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion ◽  
Electron Microscopic Autoradiography ◽  
Golgi Impregnation ◽  
Synaptic Inputs

AbstractTwo physiologically distinct, HRP-marked turtle retinal ganglion cells were examined for their morphology, GABAergic, glycinergic, and bipolar cell synaptic inputs, using electron-microscopic autoradiography and postembedding immunocytochemistry. One cell was a color-opponent, transient ON/OFF ganglion cell. Its center response to red was a sustained hyperpolarization, and its center response to green was a depolarization with increased spiking at onset. The HRP-injected cell most resembled G6, from previous Golgi-impregnation studies (Kolb, 1982; Kolb et al., 1988). It was a narrow-field bistratified cell, whose two broad dendritic strata peaked at approximately levels L20–25 (sublamina a) and L60 (sublamina b) of the inner plexiform layer. Bipolar cell synapses onto G6 were found evenly distributed between its distal and proximal dendritic strata, spanning L20–75. These inputs probably originated from several different bipolar cells, reflecting the complexity of the center response. GABAergic inputs were found onto both the distal and proximal strata, from near L20–L85. Only a few glycinergic inputs, confined to dendrites at L50–70, were observed.A second ganglion cell type that we physiologically characterized and HRP-injected had sustained ON-center, sustained OFF-surround responses. Two examples were studied; both were bistratified in sublamina b, near L60–70 and L85–100, with branches up to near L40. They resembled G10, from previous Golgi-impregnation studies (Kolb, 1982; Kolb et al., 1988). One cell was partially reconstructed to look at the distributions of GABAergic and glycinergic amacrine cell, and bipolar cell inputs. Although synapses from bipolar cells were equally divided between the two major dendritic strata of G10, the inputs to the distal stratum were close to the soma, and the inputs to the more proximal stratum were on the peripheral dendrites. This arrangement may reflect input from two distinct types of ON-bipolar cell. GABAergic and glycinergic inputs to G10 costratified to both strata and to the distal branches; but where glycinergic inputs were found distributed throughout the arbor, GABAergic inputs appeared to be confined to peripheral dendrites. We hypothesize on the neural elements involved and the circuitry that may underlie the physiologically recorded receptive fields of these two very different ganglion cell types in the turtle retina.

scholarly journals Spike-Dependent GABA Inputs to Bipolar Cell Axon Terminals Contribute to Lateral Inhibition of Retinal Ganglion Cells

2003 ◽  
Vol 89 (5) ◽  
pp. 2449-2458 ◽  
Author(s):  
Colleen R. Shields ◽  
Peter D. Lukasiewicz
Keyword(s):  
Retinal Ganglion Cells ◽  
Lateral Inhibition ◽  
Bipolar Cell ◽  
Action Potentials ◽  
Presynaptic Inhibition ◽  
Amacrine Cell ◽  
Ganglion Cells ◽  
Plexiform Layer ◽  
Bipolar Cells ◽  
Retinal Ganglion

The inhibitory surround signal in retinal ganglion cells is usually attributed to lateral horizontal cell signaling in the outer plexiform layer (OPL). However, recent evidence suggests that lateral inhibition at the inner plexiform layer (IPL) also contributes to the ganglion cell receptive field surround. Although amacrine cell input to ganglion cells mediates a component of this lateral inhibition, it is not known if presynaptic inhibition to bipolar cell terminals also contributes to surround signaling. We investigated the role of presynaptic inhibition by recording from bipolar cells in the salamander retinal slice. TTX reduced light-evoked GABAergic inhibitory postsynaptic currents (IPSCs) in bipolar cells, indicating that presynaptic pathways mediate lateral inhibition in the IPL. Photoreceptor and bipolar cell synaptic transmission were unaffected by TTX, indicating that its main effect was in the IPL. To rule out indirect actions of TTX, we bypassed lateral signaling in the outer retina by either electrically stimulating bipolar cells or by puffing kainate (KA) directly onto amacrine cell processes lateral to the recorded cell. In bipolar and ganglion cells, TTX suppressed laterally evoked IPSCs, demonstrating that both pre- and postsynaptic lateral signaling in the IPL depended on action potentials. By contrast, locally evoked IPSCs in both cell types were only weakly suppressed by TTX, indicating that local inhibition was not as dependent on action potentials. Our results show a TTX-sensitive lateral inhibitory input to bipolar cell terminals, which acts in concert with direct lateral inhibition to give rise to the GABAergic surround in ganglion cells.

Human Amniotic Fluid Promotes Retinal Pigmented Epithelial Cells' Trans-Differentiation into Rod Photoreceptors and Retinal Ganglion Cells

2011 ◽  
Vol 20 (9) ◽  
pp. 1615-1625 ◽  
Author(s):  
Shima Ghaderi ◽  
Zahra-Soheila Soheili ◽  
Hamid Ahmadieh ◽  
Maliheh Davari ◽  
Fatemeh Sanie Jahromi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Amniotic Fluid ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Human Amniotic Fluid ◽  
Rod Photoreceptors ◽  
Retinal Pigmented Epithelial Cells

Unique functional properties of the APB sensitive and insensitive rod pathways signaling light decrements in mouse retinal ganglion cells

2006 ◽  
Vol 23 (1) ◽  
pp. 127-135 ◽  
Author(s):  
GUO-YONG WANG
Keyword(s):  
Functional Properties ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Mouse Retina ◽  
Clear Cut ◽  
Types Of Information ◽  
Rod Bipolar Cells ◽  
Rod Pathway ◽  
Cone Bipolar Cells

Light decrements are mediated by two distinct groups of rod pathways in the dark-adapted retina that can be differentiated on the basis of their sensitivity to the glutamate agonist DL-2-amino-phosphonobutyric (APB). By means of the APB sensitive pathway, rods transmit light decrementsviarod bipolar cells to AII amacrine cells, then to Off cone bipolar cells, which in turn innervate the dendrites of Off ganglion cells. APB hyperpolarizes rod bipolar cells, thus blocking this rod pathway. With APB insensitive pathways, rods either directly synapse onto Off cone bipolar cells, or rods pass light decrement signal to cones by gap junctions. In the present study, whole-cell patch-clamp recordings were made from ganglion cells in the dark-adapted mouse retina to investigate the functional properties of APB sensitive and insensitive rod pathways. The results revealed several clear-cut differences between the APB sensitive and APB insensitive rod pathways. The latency of Off responses to a flashing spot of light was significantly shorter for the APB insensitive pathways than those for the APB sensitive pathway. Moreover, Off responses of the APB insensitive pathways were found to be capable of following substantially higher stimulus frequencies. Nitric oxide was found to selectively block Off responses in the APB sensitive rod pathway. Collectively, these results provide evidence that the APB sensitive and insensitive rod pathways can convey different types of information signaling light decrements in the dark-adapted retina.

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