Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus

1987 ◽  
Vol 57 (5) ◽  
pp. 1361-1382 ◽  
Author(s):  
T. E. Frumkes ◽  
T. Eysteinsson

The influence of dim diffuse adapting fields upon the sensitivity to focal photic stimulation was studied by means of intracellular recording in retinal neurons of the south african clawed frog, Xenopus and the mudpuppy, Necturus. In cones and in most horizontal and bipolar cells lacking color opponency, dim diffuse backgrounds have little influence upon the response to diffuse flicker of low (less than 2 Hz) temporal frequencies; however, with small diameter test probes of higher temporal frequencies, presentation of dim backgrounds enhance the peak-to-peak amplitude of responses to sinusoidal flicker by as much as 800%. This background enhancement effect adheres to the spectral sensitivity of the green-absorbing rod photopigment, and appears to be largely independent of the influence of the adapting field upon cone photopigment or ambient membrane potential in the recorded neuron. This effect cannot be obtained with rod-driven flicker responses. We designate this background influence on flicker, suppressive rod-cone interaction (SRCI) and attribute it to a tonic suppressive (probably inhibitory) influence of rods upon cone pathways that is removed by rod light adaptation. SRCI is also observed in the response of most sustained ON and OFF ganglion cells. However, no corresponding effect occurs in rods, color-opponent second-order neurons, ON-OFF amacrine cells, or most ON-OFF ganglion cells. The spatial and temporal limitations of SRCI observed by means of intracellular recording in amphibians are very similar to those documented by means of psychophysical or electroretinogram (ERG) procedures in a wide variety of species including humans (2, 4, 11, 22, 23, 29). SRCI most probably reflects a process that is mediated by horizontal cells. The specifics of the underlying mechanism remain unclear.

2007 ◽  
Vol 24 (4) ◽  
pp. 535-547 ◽  
Author(s):  
D.S. LEBEDEV ◽  
D.W. MARSHAK

To investigate the contributions of amacrine cells to red-green opponency, a linear computational model of the central macaque retina was developed based on a published cone mosaic. In the model, amacrine cells of ON and OFF types received input from all neighboring midget bipolar cells of the same polarity, but OFF amacrine cells had a bias toward bipolar cells whose center responses were mediated by middle wavelength sensitive cones. This bias might arise due to activity dependent plasticity because there are midget bipolar cells driven by short wavelength sensitive cones in the OFF pathway. The model midget ganglion cells received inputs from neighboring amacrine cells of both types. As in physiological experiments, the model ganglion cells showed spatially opponent responses to achromatic stimuli, but they responded to cone isolating stimuli as though center and surround were each driven by a single cone type. Without amacrine cell input, long and middle wavelength sensitive cones contributed to both the centers and surrounds of model ganglion cell receptive fields. According to the model, the summed amacrine cell input was red-green opponent even though inputs to individual amacrine cells were unselective. A key prediction is that GABA and glycine depolarize two of the four types of central midget ganglion cells; this may reflect lower levels of the potassium chloride co-transporter in their dendrites.


1999 ◽  
Vol 16 (4) ◽  
pp. 653-665 ◽  
Author(s):  
DAIYAN XIN ◽  
STEWART A. BLOOMFIELD

We studied the light-evoked responses of AII amacrine cells in the rabbit retina under dark- and light-adapted conditions. In contrast to the results of previous studies, we found that AII cells display robust responses to light over a 6–7 log unit intensity range, well beyond the operating range of rod photoreceptors. Under dark adaptation, AII cells showed an ON-center/OFF-surround receptive-field organization. The intensity–response profile of the center-mediated response component followed a dual-limbed sigmoidal function indicating a transition from rod to cone mediation as stimulus intensities were increased. Following light adaptation, the receptive-field organization of AII cells changed dramatically. Light-adapted AII cells showed both ON- and OFF-responses to stimulation of the center receptive field, but we found no evidence for an antagonistic surround. Interestingly, the OFF-center response appeared first following rapid light adaptation and was then replaced gradually over a 1–4 min period by the emerging ON-center response component. Application of the metabotropic glutamate receptor agonist APB, the ionotropic glutamate blocker CNQX, 8-bromo-cGMP, and the nitric oxide donor SNAP all showed differential effects on the various center-mediated responses displayed by dark- and light-adapted AII cells. Taken together, these pharmacological results indicated that different synaptic circuits are responsible for the generation of the different AII cell responses. Specifically, the rod-driven ON-center responses are apparently derived from rod bipolar cell synaptic inputs, whereas the cone-driven ON-center responses arise from signals crossing the gap junctions between AII cells and ON-center cone bipolar cells. Additionally, the OFF-center response of light-adapted AII cells reflects direct synaptic inputs from OFF-center cone bipolar cells to AII dendritic processes in the distal inner plexiform layer.


2018 ◽  
Vol 120 (2) ◽  
pp. 867-879 ◽  
Author(s):  
Michael D. Flood ◽  
Johnnie M. Moore-Dotson ◽  
Erika D. Eggers

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells. NEW & NOTEWORTHY We demonstrated a new aspect of dopaminergic signaling that is involved in mediating light adaptation of retinal inhibition. This D1 receptor-dependent mechanism likely acts through receptors located directly on amacrine cells, in addition to its potential role in modulating the strength of serial inhibition between amacrine cells. Our results also suggest that another D2/D4 receptor-dependent or dopamine-independent mechanism must also be involved in light adaptation of inhibition to rod bipolar cells.


1995 ◽  
Vol 12 (6) ◽  
pp. 1151-1175 ◽  
Author(s):  
E. V. Famiglietti ◽  
S. J. Sharpe

AbstractEvidence from several sources indicates that the photoreceptors of rabbit retina include rods, green cones and blue cones, and that blue-green color opponency occurs in select retinal ganglion cells. One of us (Famiglietti) has identified wide-field cone bipolar cells as probable blue-cone-selective bipolars, and type C horizontal cells as possibly connected to blue cones. We wished to extend the analysis of blue cone pathways in rabbit retina and to characterize the topographic distribution of blue and green cones. Two monoclonal antibodies raised against chicken visual pigments are reported to label medium- and long-wavelength cones (COS-1) and short-wavelength cones (OS-2) in all mammalian retinas studied thus far (Szél and colleagues). Using selective labeling with these two antibodies and a nonselective method in nasal and temporal halves of the same retinas, we have found that densities of photoreceptors vary systematically, depending upon the size of the eye and age of the animal. In ‘standard’ New Zealand rabbits of 2–3 kg (2–3 months old), rods reached a peak density of about 300,000/mm2 just dorsal to the visual streak, while cones exhibit peak density at mid-visual streak of about 18,000/mm2. Published measurements of visual acuity in rabbit are less than predicted by this calculation. The ratio of cones to rods is significantly higher in ventral retina, where the density of cones declines to a plateau of 10,000–12,000/mm2, when compared to dorsal retina, where cones are uniformly distributed at a density of about 7000/mm2. The density of OS-2 labeled (presumably “blue”) cones is uniformly low, 1000–1500/mm2, in a wide expanse that includes dorsal retina, the visual streak, and much of ventral retina, except for a region of higher density along the vertical midline. We confirm that there is a far ventral horizontal region near the perimeter that is populated exclusively by a high density (about 13,000/mm2) of OS-2-positive cones (Juliusson and colleagues). This region does not extend to the ventral retinal margin, however, where cone density drops precipitously. Transitional zones between COS-1 and OS-2 labeling, in a region of relatively high and uniform cone density, where sums of COS-1 and OS-2 labeling are higher than expected and in which weakly and strongly labeled cones are intermixed, raise questions about the identities of the visual pigment epitopes, the possibility of double labeling, and therefore the possibility of dual expression of pigments in single cones. The “inverted- T -shaped” topography of higher density OS-2 labeling raises doubts about the significance of a ventral concentration of blue cones for visual function in rabbit retina.


1996 ◽  
Vol 13 (6) ◽  
pp. 1099-1107 ◽  
Author(s):  
Péter Buzás ◽  
Sára Jeges ◽  
Robert Gábriel

AbstractThe main route of information flow through the vertebrate retina is from the photoreceptors towards the ganglion cells whose axons form the optic nerve. Bipolar cells of the frog have been so far reported to contact mostly amacrine cells and the majority of input to ganglion cells comes from the amacrines. In this study, ganglion cells of frogs from two species (Bufo marinus, Xenopus laevis) were filled retrogradely with horseradish peroxidase. After visualization of the tracer, light-microscopic cross sections showed massive labeling of the somata in the ganglion cell layer as well as their dendrites in the inner plexiform layer. In cross sections, bipolar output and ganglion cell input synapses were counted in the electron microscope. Each synapse was assigned to one of the five equal sublayers (SLs) of the inner plexiform layer. In both species, bipolar cells were most often seen to form their characteristic synaptic dyads with two amacrine cells. In some cases, however, the dyads were directed to one amacrine and one ganglion cell dendrite. This type of synapse was unevenly distributed within the inner plexiform layer with the highest occurrence in SL2 both in Bufo and Xenopus. In addition, SL4 contained also a high number of this type of synapse in Xenopus. In both species, we found no or few bipolar to ganglion cell synapses in the marginal sublayers (SLs 1 and 5). In Xenopus, 22% of the bipolar cell output synapses went onto ganglion cells, whereas in Bufo this was only 10%. We conclude that direct bipolar to ganglion cell information transfer exists also in frogs although its occurrence is not as obvious and regular as in mammals. The characteristic distribution of these synapses, however, suggests that specific type of the bipolar and ganglion cells participate in this process. These contacts may play a role in the formation of simple ganglion cell receptive fields.


1991 ◽  
Vol 7 (6) ◽  
pp. 611-618 ◽  
Author(s):  
Roberta G. Pourcho ◽  
Michael T. Owczarzak

AbstractImmunocytochemical techniques were used to localize strychnine-sensitive glycine receptors in cat retina. Light microscopy showed staining in processes ramifying throughout the inner plexiform layer and in cell bodies of both amacrine and ganglion cells. At the electron-microscopic level, receptor immunoreactivity was seen to be clustered at sites postsynaptic to amacrine cells. In contrast, bipolar cells were neither presynaptic nor postsynaptic elements at sites of glycine receptor staining. Double-label studies verified the presence of glycine immunoreactivity in amacrine terminals presynaptic to glycine receptors. These findings support a role for glycine as an inhibitory neurotransmitter in amacrine cells.


2012 ◽  
Vol 107 (7) ◽  
pp. 1795-1807 ◽  
Author(s):  
Ilya Buldyrev ◽  
Theresa Puthussery ◽  
W. Rowland Taylor

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.


1988 ◽  
Vol 59 (6) ◽  
pp. 1657-1672 ◽  
Author(s):  
F. Muller ◽  
H. Wassle ◽  
T. Voigt

1. In the intact cat eye, the responses of ganglion cells to light stimulation were recorded extracellularly and the actions of iontophoretically applied 2-amino-4-phosphonobutyrate (APB), a potent agonist at ON-bipolars, and of strychnine, a glycine antagonist, were investigated. 2. Under light-adapted conditions, the activity of ON-center ganglion cells is decreased by APB but is increased by strychnine. APB and strychnine act independently of one another. 3. The activity of light-adapted OFF-center ganglion cells is increased by APB and by strychnine. The light response remains clearly modulated. Strychnine blocks the action of simultaneously applied APB. The results are in agreement with the action of a push-pull mechanism, according to which ON-cone-bipolars provide a glycinergic input into OFF-center ganglion cells. 4. Under dark-adapted conditions, APB blocks the light responses of both ON-center and OFF-center ganglion cells. The discharge rate of ON-center ganglion cells is completely suppressed; OFF-center ganglion cells show a high maintained discharge. 5. Strychnine blocks the scotopic light response of OFF-center ganglion cells and blocks the action of simultaneously applied APB. The light response of ON-center ganglion cells is hardly affected by strychnine. 6. The effects of strychnine on OFF-center ganglion cells are in agreement with the hypothesis that the glycinergic AII amacrine cells modulate the activity of the scotopic OFF-channel. 7. Intravitreally applied APB abolished the scotopic b-wave of the electroretinogram at concentrations of 100 microM. 8. Our data suggest that as in rabbit (10) the rod bipolars in cat retina are depolarizing (ON) bipolar cells.


2010 ◽  
Vol 103 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Erika D. Eggers ◽  
Peter D. Lukasiewicz

While connections between inhibitory interneurons are common circuit elements, it has been difficult to define their signal processing roles because of the inability to activate these circuits using natural stimuli. We overcame this limitation by studying connections between inhibitory amacrine cells in the retina. These interneurons form spatially extensive inhibitory networks that shape signaling between bipolar cell relay neurons to ganglion cell output neurons. We investigated how amacrine cell networks modulate these retinal signals by selectively activating the networks with spatially defined light stimuli. The roles of amacrine cell networks were assessed by recording their inhibitory synaptic outputs in bipolar cells that suppress bipolar cell output to ganglion cells. When the amacrine cell network was activated by large light stimuli, the inhibitory connections between amacrine cells unexpectedly depressed bipolar cell inhibition. Bipolar cell inhibition elicited by smaller light stimuli or electrically activated feedback inhibition was not suppressed because these stimuli did not activate the connections between amacrine cells. Thus the activation of amacrine cell circuits with large light stimuli can shape the spatial sensitivity of the retina by limiting the spatial extent of bipolar cell inhibition. Because inner retinal inhibition contributes to ganglion cell surround inhibition, in part, by controlling input from bipolar cells, these connections may refine the spatial properties of the retinal output. This functional role of interneuron connections may be repeated throughout the CNS.


2012 ◽  
Vol 107 (10) ◽  
pp. 2649-2659 ◽  
Author(s):  
A. Cyrus Arman ◽  
Alapakkam P. Sampath

The nervous system frequently integrates parallel streams of information to encode a broad range of stimulus strengths. In mammalian retina it is generally believed that signals generated by rod and cone photoreceptors converge onto cone bipolar cells prior to reaching the retinal output, the ganglion cells. Near absolute visual threshold a specialized mammalian retinal circuit, the rod bipolar pathway, pools signals from many rods and converges on depolarizing (AII) amacrine cells. However, whether subsequent signal flow to OFF ganglion cells requires OFF cone bipolar cells near visual threshold remains unclear. Glycinergic synapses between AII amacrine cells and OFF cone bipolar cells are believed to relay subsequently rod-driven signals to OFF ganglion cells. However, AII amacrine cells also make glycinergic synapses directly with OFF ganglion cells. To determine the route for signal flow near visual threshold, we measured the effect of the glycine receptor antagonist strychnine on response threshold in fully dark-adapted retinal cells. As shown previously, we found that response threshold for OFF ganglion cells was elevated by strychnine. Surprisingly, strychnine did not elevate response threshold in any subclass of OFF cone bipolar cell. Instead, in every OFF cone bipolar subclass strychnine suppressed tonic glycinergic inhibition without altering response threshold. Consistent with this lack of influence of strychnine, we found that the dominant input to OFF cone bipolar cells in darkness was excitatory and the response threshold of the excitatory input varied by subclass. Thus, in the dark-adapted mouse retina, the high absolute sensitivity of OFF ganglion cells cannot be explained by signal transmission through OFF cone bipolar cells.


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