Receptive field of the retinal bipolar cell: a pharmacological study in the tiger salamander

1996 ◽  
Vol 76 (3) ◽  
pp. 2005-2019 ◽  
Author(s):  
W. A. Hare ◽  
W. G. Owen

1. It is widely believed that signals contributing to the receptive field surrounds of retinal bipolar cells pass from horizontal cells to bipolar cells via GABAergic synapses. To test this notion, we applied gamma-aminobutyric acid (GABA) agonists and antagonists to isolated, perfused retinas of the salamander Ambystoma tigrinum while recording intracellularly from bipolar cells, horizontal cells, and photoreceptors. 2. As we previously reported, administration of the GABA analogue D-aminovaleric acid in concert with picrotoxin did not block horizontal cell responses or the center responses of bipolar cells but blocked the surround responses of both on-center and off-center bipolar cells. 3. Surround responses were not blocked by the GABA, antagonists picrotoxin or bicuculline, the GABAB agonist baclofen or the GABAB antagonist phaclofen, and the GABAC antagonists picrotoxin or cis-4-aminocrotonic acid. Combinations of these drugs were similarly ineffective. 4. GABA itself activated a powerful GABA uptake mechanism in horizontal cells for which nipecotic acid is a competitive agonist. It also activated, both in horizontal cells and bipolar cells, large GABAA conductances that shunted light responses but that could be blocked by picrotoxin or bicuculline. 5. GABA, administered together with picrotoxin to block the shunting effect of GABAA activation, did not eliminate bipolar cell surround responses at concentrations sufficient to saturate the known types of GABA receptors. 6. Surround responses were not blocked by glycine or its antagonist strychnine, or by combinations of drugs designed to eliminate GABAergic and glycinergic pathways simultaneously. 7. Although we cannot fully discount the involvement of a novel GABAergic synapse, the simplest explanation of our findings is that the primary pathway mediating the bipolar cell's surround is neither GABAergic nor glycinergic.

1991 ◽  
Vol 65 (3) ◽  
pp. 680-692 ◽  
Author(s):  
R. A. Stockton ◽  
M. M. Slaughter

1. The effects of inhibitory amino acid transmitters on horizontal cells in the superfused amphibian retina were studied by the use of conventional intracellular recording techniques. 2. Gamma-aminobutyric acid (GABA) caused a calcium-independent depolarization of horizontal cells in mud puppy and tiger salamander. This action was mimicked by muscimol but not baclofen (BAC) and blocked by bicuculline and picrotoxin (PTX), matching the GABAa receptor profile. 3. The purported GABA uptake inhibitors nipecotate (NPA) and guvacine (GUV) acted as GABAa agonists, having pharmacological properties very similar to GABA itself. These agents also activated receptors of amacrine and ganglion cells, causing membrane polarizations similar to GABA. Concentrations of these analogues that did not activate the GABAa receptor (submillimolar) did not lower the effective dose of GABA, even after prolonged application. 4. Glycine (GLY) also depolarized horizontal cells, but only in approximately 25% of the horizontal cells was the amplitude of the depolarization as great as GABA. The glycine response was blocked by both strychnine (STR, 10 microM) and PTX (100 microM). In contrast, the action of GABA was unaffected by STR. 5. Ion substitution and channel-blocking agents indicated that the effects of applied GABA and GLY were independent of both external sodium and calcium. 6. The results suggest that GABA receptors on horizontal cells may act 1) as a positive feedback system to modulate the light response and 2) as a mechanism for chemical coupling between horizontal cells.


1999 ◽  
Vol 16 (5) ◽  
pp. 801-809 ◽  
Author(s):  
SILKE HAVERKAMP ◽  
WOLFGANG MÖCKEL ◽  
JOSEF AMMERMÜLLER

Electrophysiologically, color-opponent retinal bipolar cells respond with opposite polarities to stimulation with different wavelengths of light. The origin of these different polarities in the same bipolar cell has always been a mystery. Here we show that an intracellularly recorded and HRP-injected, red-ON, blue/green-OFF bipolar cell of the turtle retina made invaginating (ribbon associated) synapses exclusively with L-cones. Non-invaginating synapses resembling wide-cleft basal junctions were made exclusively with M-cones. Input from S-cones was not seen. From these results we suggest sign-inverting transmission from L-cones at invaginating synapses via metabotropic glutamate receptors, and sign-conserving transmission from M-cones at wide-cleft basal junctions via ionotropic receptors. To explain the pronounced blue sensitivity of the bipolar cell, computer simulations were performed using a sign-conserving input from a yellow/blue chromaticity-type (H3) horizontal cell. The response properties of the red-ON, blue/green-OFF bipolar cell could be quantitatively reproduced by this means. The simulation also explained the asymmetry in L- and M-cone inputs to the bipolar cell as found in the ultrastructural analysis and assigned a putative role to H3 horizontal cells in color processing in the turtle retina.


1999 ◽  
Vol 16 (3) ◽  
pp. 503-511 ◽  
Author(s):  
R.A. SHIELLS ◽  
G. FALK

Simultaneous extracellular ERG and intracellular recordings from horizontal and ON-bipolar cells were obtained from the dark-adapted retina of the dogfish. The light intensity–peak response relation (IR) and time course of on-bipolar cell responses closely resembled that of the ERG b-wave, but only at low light intensities [<10 rhodopsin molecules bleached per rod (Rh*)]. Block of on-bipolar cell responses with 50 μM 2-amino-4-phosphonobutyrate (APB) abolished the b-wave and unmasked a vitreal-negative wave. Subtraction from the control ERG resulted in the isolation of a vitreal-positive ERG with an IR which matched that of on-bipolar cells over the full range of light intensities. The D.C. component of the ERG arises as a result of sustained depolarization of on-bipolar cells in response to long (>0.5 s) dim light stimuli, or following bright light flashes. The IR of horizontal cells and the vitreal-negative wave unmasked by APB could be matched by scaling at low light intensities (<5 Rh*). However, horizontal cell responses saturated at about 30 Rh*, while the vitreal-negative wave continued to increase in amplitude. The time course of horizontal cell membrane current with dim flashes could be matched to the rising phase of the vitreal-negative wave, assuming that the delay in generating the voltage response in horizontal cells is due to their long (100 ms) membrane time constant. Blocking post-photoreceptor activity resulted in a much smaller vitreal-negative wave than that unmasked by APB alone. We conclude that the b-wave arises from on-bipolar cell depolarization, while the leading edge of the a-wave is a composite of the change in extracellular voltage drop across the rod layer and a component (proximal PIII) reflecting a decrease in extracellular K+ as horizontal cell synaptic channels close with light.


1982 ◽  
Vol 79 (1) ◽  
pp. 131-145 ◽  
Author(s):  
J Toyoda ◽  
T Kujiraoka

Simultaneous intracellular recordings were made from a bipolar cell and a horizontal cell in the carp retina. The properties of the bipolar cell were studied while injecting current into the horizontal cell. Hyperpolarization of horizontal cells, irrespective of their type, elicited a hyperpolarizing response in on-center bipolar cells and a depolarizing response in off-center bipolar cells. Analyses of the ionic mechanisms of bipolar cell responses revealed that depolarization of horizontal cells simulated and hyperpolarization opposed the effect of central illumination. The effect of polarization was exerted in such a manner that each type of horizontal cells modified the transmission from those photoreceptors from which they receive main inputs. In on-center bipolar cells, for example, the L-type horizontal cells receiving inputs mainly from red cones modified the cone-bipolar transmission accompanied by a conductance change of K+ and/or Cl- channels, and the intermediate horizontal cells receiving inputs from rods modified the rod-bipolar transmission accompanied by a conductance change of Na+ channels. In off-center bipolar cells, the effect of polarization of any type of horizontal cells was mediated mainly by conductance changes of Na+ channels. Feedback mechanisms from horizontal cells to photoreceptors could explain these results reasonably well.


1981 ◽  
Vol 211 (1184) ◽  
pp. 373-389 ◽  

A serial section analysis of photoreceptor synaptic bases was undertaken in the clawed frog Xenopus laevis . The developmental period from tadpole stage 48 through metamorphosis was studied. Horizontal cells contacted rod and cone photoreceptors at ribbon synapses; the number of such contacts per receptor base was constant for rods, but increased for cones as a function-of developmental stage. In pre-metamorphic animals bipolar cells contacted receptors only through basal junctions; their number in cone bases increased dramatically during development but was unchanged in rod bases. A densitometric estimation of the cleft width of basal junctions showed that it ranged from 10 to 18 nm, but the junctions could not be divided reliably into the ‘wide’ and ‘narrow’ categories reported for other vertebrate species. Near metamorphic climax a new type of ribbon-related bipolar cell junction appeared. Gap junctions between horizontal cells and conventional chemical synapses of horizontal cell onto bipolar cell processes were first seen in mid-larval developmental stages.


The organization of the outer synaptic layer in the salamander retina was studied electronmicroscopically in serial sections of tissue prepared by conventional techniques or stained by the method of Golgi. Rod cell pedicles make ribbon junctions on cone cell processes, and rod cell processes invaginate cone pedicles without otherwise making any specialized contact with them. Horizontal cells make ribbon and distal junctions with the photoreceptor cell pedicles; a single horizontal cell may contact both rods and cones. Bipolar cells were observed to make either ribbon or basal junctions with the photoreceptor cell pedicles; in addition, certain processes believed to belong to bipolar cells make both ribbon and basal junctions with the same or different pedicles. A single bipolar cell may make contact with both rods and cones. Horizontal cells synapse on bipolar cell dendrites and on certain unidentified processes which in turn are also presynaptic to bipolar cells. Ascending branches of these processes invaginate deeply the rod and cone pedicles without otherwise engaging them in any junction. Horizontal cell processes are linked by two kinds of junctions: close membrane appositions, and contacts analogous to the distal junctions between horizontal cells and rod pedicles.


1992 ◽  
Vol 67 (2) ◽  
pp. 364-372 ◽  
Author(s):  
C. J. Dong ◽  
J. S. McReynolds

1. The effects of flickering adapting illumination (repetitive flashes) on horizontal cell responses to illumination of the center and surround portions of the receptive field were compared with those of steady adapting illumination in dark-adapted mudpuppy retinas. 2. Exposure to flickering adapting light caused an increase in amplitude of responses to small spots in the receptive-field center and a decrease in the response to a concentric annulus. This is interpreted as due to an increase in coupling resistance between horizontal cells. 3. The uncoupling effect of flickering adapting light was no greater than that of the same quantity of steady adapting light at the same intensity, even when the rate of flickering was varied by a factor of 10. 4. The uncoupling effect of flickering light was blocked by the dopamine antagonists fluphenazine and SCH23390, indicating that it is mediated by dopamine release. 5. The uncoupling effect of flickering light was also blocked in the presence of 2-amino-4-phosphonobutyrate (APB), which prevents light responses of on-center but not off-center bipolar cells, suggesting that flickering light increases dopamine release via the on-pathway. 6. The gamma-aminobutyric acid (GABA) antagonist bicuculline had an uncoupling effect similar to that of adapting illumination. This effect was blocked by dopamine antagonists, indicating that there is tonic GABA-mediated inhibition of dopamine release in mudpuppy retina similar to that previously reported by others in fish and turtle retinas. 7. The uncoupling effect of bicuculline was not reversed by APB. However, APB alone caused an increase in coupling that was rapidly reversed by bicuculline.(ABSTRACT TRUNCATED AT 250 WORDS)


2019 ◽  
Author(s):  
Christian Behrens ◽  
Yue Zhang ◽  
Shubhash Chandra Yadav ◽  
Silke Haverkamp ◽  
Stephan Irsen ◽  
...  

AbstractIn the outer plexiform layer (OPL) of the mouse retina, two types of cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). This transmission is modulated by a single horizontal cell (HC) type, the only interneuron in the outer retina. Horizontal cells form feedback synapses with cones and feedforward synapses with CBCs. However, the exact computational role of HCs is still debated. Along with performing global signaling within their laterally coupled network, HCs also provide local, cone-specific feedback. Specifically, it has not been clear which synaptic structures HCs use to provide local feedback to cones and global forward signaling to CBCs.Here, we reconstructed in a serial block-face electron microscopy volume the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites to quantitatively analyze their connectivity. In addition to the fine HC dendritic tips invaginating cone axon terminals, we also identified “bulbs”, short segments of increased dendritic diameter on the primary dendrites of HCs. These bulbs are located well below the cone axon terminal base and make contact to other cells mostly identified as other HCs or CBCs. Using immunolabeling we show that HC bulbs express vesicular gamma-aminobutyric acid transporters and co-localize with GABA receptor γ2 subunits. Together, this suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysics-based computational model of a HC dendritic branch supports the hypothesis that the spatial arrangement of synaptic contacts allows simultaneous local feedback and global feedforward signaling.


1991 ◽  
Vol 66 (6) ◽  
pp. 2002-2013 ◽  
Author(s):  
T. A. Gilbertson ◽  
S. Borges ◽  
M. Wilson

1. Horizontal cells, identified by their morphology, were isolated from the salamander retina and examined in whole cell patch clamp. 2. All cells showed large outward currents activating positive to about -50 mV, and a minority of cells showed fast, tetrodotoxin-suppressible Na+ currents. Slow inward currents that might shape the light responses were never observed. 3. All cells showed conductance increases to both gamma-aminobutyric acid (GABA) and glycine that were completely blocked by bicuculline and strychnine, respectively. No cross-blocking by these antagonists was observed. Partial replacements of Cl- with large, impermeant anions indicated that both GABA- and glycine-evoked currents were carried by Cl- ions. 4. Responses to both GABA and glycine desensitized strongly with time constants of approximately 2 s. 5. Responses to glutamate were not enhanced by glycine. Similarly, responses to GABA were not enhanced by glutamate. 6. GABA-mediated synaptic interactions between horizontal cells may account for the changes in the kinetics of horizontal cell light responses seen when glycine is applied to the intact retina.


1999 ◽  
Vol 115 (1) ◽  
pp. 3-16 ◽  
Author(s):  
D.A. Kraaij ◽  
H. Spekreijse ◽  
M. Kamermans

Cones in the vertebrate retina project to horizontal and bipolar cells and the horizontal cells feedback negatively to cones. This organization forms the basis for the center/surround organization of the bipolar cells, a fundamental step in the visual signal processing. Although the surround responses of bipolar cells have been recorded on many occasions, surprisingly, the underlying surround-induced responses in cones are not easily detected. In this paper, the nature of the surround-induced responses in cones is studied. Horizontal cells feed back to cones by shifting the activation function of the calcium current in cones to more negative potentials. This shift increases the calcium influx, which increases the neurotransmitter release of the cone. In this paper, we will show that under certain conditions, in addition to this increase of neurotransmitter release, a calcium-dependent chloride current will be activated, which polarizes the cone membrane potential. The question is, whether the modulation of the calcium current or the polarization of the cone membrane potential is the major determinant for feedback-mediated responses in second-order neurons. Depolarizing light responses of biphasic horizontal cells are generated by feedback from monophasic horizontal cells to cones. It was found that niflumic acid blocks the feedback-induced depolarizing responses in cones, while the shift of the calcium current activation function and the depolarizing biphasic horizontal cell responses remain intact. This shows that horizontal cells can feed back to cones, without inducing major changes in the cone membrane potential. This makes the feedback synapse from horizontal cells to cones a unique synapse. Polarization of the presynaptic (horizontal) cell leads to calcium influx in the postsynaptic cell (cone), but due to the combined activity of the calcium current and the calcium-dependent chloride current, the membrane potential of the postsynaptic cell will be hardly modulated, whereas the output of the postsynaptic cell will be strongly modulated. Since no polarization of the postsynaptic cell is needed for these feedback-mediated responses, this mechanism of synaptic transmission can modulate the neurotransmitter release in single synaptic terminals without affecting the membrane potential of the entire cell.


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