scholarly journals Nonlinear transfer and temporal gain control in ON bipolar cells

2019 ◽  
Author(s):  
Nikhil R. Deshmukh ◽  
Michael J. Berry
Keyword(s):  
Bipolar Cell ◽  
Time Course ◽  
Gain Control ◽  
Outward Current ◽  
Opposite Polarity ◽  
Bipolar Cells ◽  
Visual Signal ◽  
High Contrast ◽  
Full Field ◽  
Discrete Channels

AbstractThe separation of visual input into discrete channels begins at the photoreceptor to bipolar cell synapse. Current models of the ON pathway describe the time-varying membrane voltage of ON bipolar cells as a linear function of light fluctuations. While this linearity holds under some visual conditions, stimulating the retina with full-field, high contrast flashes reveals a number of nonlinearities already present in the input current of ON bipolar cells. First, we show that the synaptic input to ON bipolar cells is asymmetric in response to equal flashes of opposite polarity. Next, we show that this asymmetry emerges because the responses to dark flashes increase linearly with contrast, whereas responses to bright flashes are highly rectified. We also describe how the outward current saturates in response to dark flashes of increasing duration. Furthermore, varying the inter-flash interval between a pair of high contrast flashes reveals a rapid, transient form of gain control that modulates both the amplitude and time course of the flash response. We develop a phenomenological model that captures the primary features of the ON bipolar cell response at high contrast. Finally, we discuss the implications of these nonlinearities in our understanding of how retinal circuitry shapes the visual signal.

Contribution of rod, on-bipolar, and horizontal cell light responses to the ERG of dogfish retina

1999 ◽  
Vol 16 (3) ◽  
pp. 503-511 ◽  
Author(s):  
R.A. SHIELLS ◽  
G. FALK
Keyword(s):  
Bipolar Cell ◽  
Time Course ◽  
Horizontal Cell ◽  
Full Range ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Negative Wave ◽  
Low Light ◽  
Cell Responses ◽  
Light Intensities

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.

GABA- and glycine-activated currents in the rod bipolar cell of the rabbit retina

1995 ◽  
Vol 74 (2) ◽  
pp. 856-875 ◽  
Author(s):  
M. A. Gillette ◽  
R. F. Dacheux
Keyword(s):  
Gabaa Receptor ◽  
Bipolar Cell ◽  
Reversal Potential ◽  
Outward Current ◽  
Bipolar Cells ◽  
Morphological Identification ◽  
Response Curves ◽  
Patch Clamp Technique ◽  
T Distribution ◽  
Rod Bipolar Cells

1. Voltage- and ligand-gated currents were recorded from solitary rabbit rod bipolar cells using the whole cell patch-clamp technique. The rod bipolar cell forms a single, stereotypical physiological and morphological class of cells that was easily identified from other neurons and support cells after enzymatic and mechanical dissociation from isolated retina. Protein kinase C immunoreactivity confirmed the validity of using a purely morphological identification of this cell type. 2. Voltage steps in 15-mV increments from a holding potential of -45 mV elicited a large outward current activated near -30 mV. These voltage-gated currents were eliminated by using equimolar substitutions of Cs+ and tetraethylammonium+ for K+ in the pipette, indicating that they represent a mixture of K+ currents. 3. The putative inhibitory neurotransmitters gamma-aminobutyric acid (GABA) and glycine activated inward Cl- currents when pressure-applied from pipettes placed near the axon terminals of rod bipolar cells, which were voltage-clamped at -45 mV. With changes in intracellular or extracellular Cl- concentration, the reversal potential of these ligand-gated currents changed as predicted by the Nernst equation for Cl- activity. The dose-response curves for GABA and glycine were sigmoidal with saturating concentrations of 100 and 300 microM, respectively. 4. GABA-activated currents were 1) reversibly reduced by the allosteric inhibitor picrotoxin and the competitive antagonist bicuculline; 2) potentiated by the benzodiazepine diazepam and the barbiturate barbital sodium; and 3) indistinguishable from muscimol-activated currents. There was no response to the GABAB agonist baclofen. Collectively, these data strongly suggest that the GABA-activated currents in rabbit rod bipolar cells are mediated by the GABAA receptor. This is similar to the GABA-activated currents in other mammalian rod bipolar cells. 5. Application of the conformationally restricted GABA analogue cis-4-aminocrotonic acid (CACA) failed to elicit a response, whereas the conformationally extended GABA analogue trans-4-aminocrotonic acid (TACA) elicited a response similar to that of GABA. Although bicuculline appeared to suppress the GABA-activated current slightly more than the TACA-activated current (not significant using Student's t-distribution), GABA- and TACA-activated currents were equally suppressed by picrotoxin and equally enhanced by diazepam and barbital sodium. These data, coupled with the inefficacy of CACA, argue against the existence of a GABAC-type channel in the rod bipolar cell of the rabbit and suggest that GABA and TACA were activating the same GABAA receptor-channel complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence and divergence of cones onto bipolar cells in the central area of cat retina

1990 ◽  
Vol 330 (1258) ◽  
pp. 323-328 ◽  
Keyword(s):  
Bipolar Cell ◽  
Central Area ◽  
Plexiform Layer ◽  
Preceding Paper ◽  
Bipolar Cells ◽  
Visual Signal ◽  
Wide Field ◽  
Inner Plexiform Layer ◽  
Type B ◽  
Cat Retina

In the central area of cat retina the cone bipolar cells that innervate sublamina b of the inner plexiform layer comprise five types, four with narrow dendritic fields and one with a wide dendritic field. This was shown in the preceding paper (Cohen & Sterling 1990 a ) by reconstruction from electron micrographs of serial sections. Here we show by further analysis of the same material that the coverage factor (dendritic spread x cell density) is about one for each of the narrow-field types (b 1 , b 2 , and b 4 ). The same is probably true for the other narrow-field type (b 3 ), but this could not be proved because its dendrites were too fine to trace. The dendrites of types b 1 , b 2 , and b 4 collect from all the cone pedicles within their reach and do not bypass local pedicles in favour of more distant ones. The dendrites of type b 5 , the wide-field cell, bypass many pedicles. On average 5.1±1.0 pedicles converge on a b 1 bipolar cell; 6.0±1.2 converge on a b 2 cell and 5.7±1.5 converge on a b 4 cell. Divergence within a type is minimal: one pedicle contacts only 1.2 b 1 cells, 1.0 b 2 cells, and 1.0 b 4 cells. Divergence across types is broad : each pedicle apparently contacts all four types of the narrow-field bipolar cells that innervate sublamina b . Each pedicle probably also contacts an additional 4—5 types of narrow-field bipolar cell that innervate sublamina a . There are several possible advantages to encoding the cone signal into multiple, parallel, narrow-field pathways. These include: tuning of pathways to transmit different temporal frequencies, use of ion channels with widely separated equilibrium potentials (to increase gain), and formation of different regulatory circuits in the inner plexiform layer. The latter possibility would permit different operations (e.g linear or nonlinear) to be performed on the visual signal on its way towards different types of ganglion cell.

Rabbit cone bipolar cells: Correlation of their morphologies with whole-cell recordings

2001 ◽  
Vol 18 (5) ◽  
pp. 675-685 ◽  
Author(s):  
GREGORY S. McGILLEM ◽  
RAMON F. DACHEUX
Keyword(s):  
Glutamate Receptor ◽  
Bipolar Cell ◽  
Receptor Agonist ◽  
Metabotropic Glutamate Receptor ◽  
Outward Current ◽  
Membrane Resistance ◽  
Bipolar Cells ◽  
Kainate Receptor ◽  
Whole Cell ◽  
Cone Bipolar Cells

The superfused retinal slice preparation was used to examine the morphology and glutamate-activated whole-cell currents of rabbit bipolar cells. There were six morphologically distinct types of cone bipolar cells and a rod bipolar cell that had axon terminals stratifying in stratum 3 to 5 of sublamina-b. All of these bipolar cell types exhibited an outward current in response to the application of the metabotropic glutamate receptor, mGluR6, agonist AP-4 (APB), and had I/V curves indicative of membrane channel closure. Conversely, there were no currents activated during the application of kainate, the AMPA/kainate receptor agonist. These data demonstrate they were on-bipolar cells. In addition, there were six morphologically distinct cone bipolar cells that stratified in sublamina-a. Every cell with axonal arborizations in stratum 1 and 2 exhibited an inward current when the ionotropic glutamate receptor agonist kainate was applied. This current was blocked by application of the AMPA/kainate receptor antagonist CNQX. These cells also decreased their membrane resistance in response to kainate, a characteristic of the opening of channels within the plasma membrane. Without exception, no cells stratifying in sublamina-a responded to the mGluR6 agonist AP-4, further identifying them as off-bipolar cells.

scholarly journals Genetic targeting and physiological features of VGLUT3+ amacrine cells

2011 ◽  
Vol 28 (5) ◽  
pp. 381-392 ◽  
Author(s):  
WILLIAM N. GRIMES ◽  
REBECCA P. SEAL ◽  
NICHOLAS OESCH ◽  
ROBERT H. EDWARDS ◽  
JEFFREY S. DIAMOND
Keyword(s):  
Time Course ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Glutamate Transporter ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Membrane Properties ◽  
Visual Signal ◽  
Transgenic Mouse Line ◽  
Electrophysiological Recordings

AbstractAmacrine cells constitute a diverse class of interneurons that contribute to visual signal processing in the inner retina, but surprisingly, little is known about the physiology of most amacrine cell subtypes. Here, we have taken advantage of the sparse expression of vesicular glutamate transporter 3 (VGLUT3) in the mammalian retina to target the expression of yellow fluorescent protein (YFP) to a unique population of amacrine cells using a new transgenic mouse line. Electrophysiological recordings made from YFP-positive (VGLUT3+) amacrine cells provide the first functional data regarding the active membrane properties and synaptic connections of this recently identified cell type. We found that VGLUT3+ amacrine cells receive direct synaptic input from bipolar cells via both N-methyl-d-aspartate receptors (NMDARs) and non-NMDARs. Voltage-gated sodium channels amplified these excitatory inputs but repetitive spiking was never observed. VGLUT3+ amacrine cells responded transiently to both light increments (ON response) and decrements (OFF response); ON responses consisted exclusively of inhibitory inputs, while OFF responses comprised both excitatory and inhibitory components, although the inhibitory conductance was larger in amplitude and longer in time course. The physiological properties and anatomical features of the VGLUT3+ amacrine cells suggest that this bistratified interneuron may play a role in disinhibitory signaling and/or crossover inhibition between parallel pathways in the retina.

scholarly journals VOLTAGE-GATED POTASSIUM CHANNELS CONTROL THE GAIN OF ROD-DRIVEN LIGHT RESPONSES IN MIXED-INPUT ON BIPOLAR CELLS

2020 ◽  
Author(s):  
Christina Joselevitch ◽  
Jan Klooster ◽  
Maarten Kamermans
Keyword(s):  
Potassium Channels ◽  
Bipolar Cell ◽  
Gain Control ◽  
Bipolar Cells ◽  
Transient Signal ◽  
List Type ◽  
Light Responses ◽  
Voltage Gated ◽  
Light Levels ◽  
Slow Kinetics

AbstractTo achieve high sensitivity at scotopic levels, vision sacrifices spatial and temporal resolution. The detection of dim light, however, depends crucially on the ability of the visual system to speed up rod signals as they advance towards the brain. At higher light levels, gain control mechanisms are necessary to prevent premature saturation of second-order neurons. We investigated how goldfish mixed-input ON bipolar cells (ON mBCs) manage to partially compensate for the intrinsically slow kinetics of rod signals in the dark-adapted state, and at the same time control the gain of rod signals. Rod-driven responses of axotomized ON mBCs become faster and more transient than those of rod horizontal cells as stimulus intensity increases. This transientness has a voltage-dependency consistent with the activation of a voltage-gated K+ conductance. Simulations with NEURON indicate that the voltage-gated K+ channels responsible for speeding up responses are concentrated at the distal tips of the bipolar cell dendrites, close to the glutamate receptors. These channels act as a gain control mechanism, by shunting the effect of tonically hyperpolarized rods onto the ON mBC. Further activation of K+ channels accelerates the ON mBC response by decreasing the membrane time constant as light levels increase. Therefore, the presence of voltage-gated K+ channels at the dendritic tips of ON mBCs extends the dynamic range of these neurons, and at the same time generates a transient signal already at the first visual synapse.Key Points SummaryHere we show that voltage-gated potassium channels can adjust the gain of the rod input to mixed-input ON bipolar cells and generate a transient signal already at the first visual synapse.These channels are activated during the light-induced depolarization, making bipolar cell light responses smaller, faster, and more transient, effects that can be abolished by the K+ channel blocker TEA.Mathematical simulations suggest that these channels are concentrated at the bipolar cell dendritic tips, close to the site of rod input.This kind of gain control happens at all levels in the retina and is especially important for cells that receive mixed input from rods and cones, in order to prevent premature saturation with increasing light levels and remove the temporal redundancy of the photoreceptor signal.

Response linearity and kinetics of the cat retina: The bipolar cell component of the dark-adapted electroretinogram

1995 ◽  
Vol 12 (5) ◽  
pp. 837-850 ◽  
Author(s):  
J. G. Robson ◽  
L. J. Frishman
Keyword(s):  
Bipolar Cell ◽  
Time Course ◽  
Temporal Integration ◽  
Leading Edge ◽  
Bipolar Cells ◽  
Neuronal Responses ◽  
Cat Retina ◽  
Wide Range ◽  
Three Stages ◽  
Fixed Times

AbstractThe electroretinogram (ERG) of the dark-adapted cat eye in response to brief ganzfeld flashes of a wide range of intensities was recorded after intravitreal injection of n-methyl dl aspartate (NMdlA, cumulative intravitreal concentration of 1.3–3.9 mM) to suppress inner-retinal components, and after intravitreal dl or L-2-amino-4-phosphonobutyric acid (dl-APB, 1–3 mM; l-APB, 1.2 mM) and 6-cyano-7-nitroquinoxaline-2, 3 dione (CNQX, 40–60 µM), to suppress all post-receptoral neuronal responses. Rod PII, the ERG component arising from rod bipolar cells, was derived by subtracting records obtained after APB and CNQX from post-NMDLA records. When we measured the derived response at fixed times after the stimulus, we found that PII initially increased in proportion to stimulus intensity without any sign of a threshold. The leading edge of PII at early times after the stimulus, when the response was still small, was well described by V(t) = kI(t −td)5 where k is a constant, I is the intensity of the stimulus, and td is a brief delay of about 3 ms. Correspondingly, the time for the response to rise to an arbitrary small criterion voltage Vcrit was adequately fitted by tcrit = td + (Vcrit/kI)1/5. The time course of the leading edge of the PII response can be interpreted to indicate that the mechanism generating PII introduces three stages of temporal integration in addition to the three stages that are provided by the mechanism of the rod photoreceptors. This finding is consistent with the operation within the rod bipolar cell of a G-protein cascade similar to that in the rods.

scholarly journals Slow changes in Ca2+ cause prolonged release from GABAergic retinal amacrine cells

2013 ◽  
Vol 110 (3) ◽  
pp. 709-719 ◽  
Author(s):  
Erika D. Eggers ◽  
Justin S. Klein ◽  
Johnnie M. Moore-Dotson
Keyword(s):  
Bipolar Cell ◽  
Neurotransmitter Release ◽  
Time Course ◽  
Amacrine Cell ◽  
Glutamate Release ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Prolonged Release ◽  
Deconvolution Analysis ◽  
Presynaptic Mechanisms

The timing of neurotransmitter release from neurons can be modulated by many presynaptic mechanisms. The retina uses synaptic ribbons to mediate slow graded glutamate release from bipolar cells that carry photoreceptor inputs. However, many inhibitory amacrine cells, which modulate bipolar cell output, spike and do not have ribbons for graded release. Despite this, slow glutamate release from bipolar cells is modulated by slow GABAergic inputs that shorten the output of bipolar cells, changing the timing of visual signaling. The time course of light-evoked inhibition is slow due to a combination of receptor properties and prolonged neurotransmitter release. However, the light-evoked release of GABA requires activation of neurons upstream from the amacrine cells, so it is possible that prolonged release is due to slow amacrine cell activation, rather than slow inherent release properties of the amacrine cells. To test this idea, we directly activated primarily action potential-dependent amacrine cell inputs to bipolar cells with electrical stimulation. We found that the decay of GABAC receptor-mediated electrically evoked inhibitory currents was significantly longer than would be predicted by GABAC receptor kinetics, and GABA release, estimated by deconvolution analysis, was inherently slow. Release became more transient after increasing slow Ca2+ buffering or blocking prolonged L-type Ca2+ channels and Ca2+ release from intracellular stores. Our results suggest that GABAergic amacrine cells have a prolonged buildup of Ca2+ in their terminals that causes slow, asynchronous release. This could be a mechanism of matching the time course of amacrine cell inhibition to bipolar cell glutamate release.

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
Keyword(s):  
Receptive Field ◽  
Gaba Receptors ◽  
Bipolar Cell ◽  
Horizontal Cell ◽  
Pharmacological Study ◽  
Bipolar Cells ◽  
Horizontal Cells ◽  
Gaba Uptake ◽  
Gamma Aminobutyric Acid ◽  
Gabaergic Synapse

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.

scholarly journals Charge Movement Associated with the Opening and Closing of the Activation Gates of the Na Channels

1974 ◽  
Vol 63 (5) ◽  
pp. 533-552 ◽  
Author(s):  
Clay M. Armstrong ◽  
Francisco Bezanilla
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Close Association ◽  
Outward Current ◽  
Transient Outward Current ◽  
Activation Process ◽  
Charge Movement ◽  
Gating Current ◽  
Dipolar Molecules ◽  
Opening And Closing

The sodium current (INa) that develops after step depolarization of a voltage clamped squid axon is preceded by a transient outward current that is closely associated with the opening of the activation gates of the Na pores. This "gating current" is best seen when permeant ions (Na and K) are replaced by relatively impermeant ones, and when the linear portion of capacitative current is eliminated by adding current from positive steps to that from exactly equal negative ones. During opening of the Na pores gating current is outward, and as the pores close there is an inward tail of current that decays with approximately the same time-course as INa recorded in Na-containing medium. Both outward and inward gating current are unaffected by tetrodotoxin (TTX). Gating current is capacitative in origin, the result of relatively slow reorientation of charged or dipolar molecules in a suddenly altered membrane field. Close association with the Na activation process is clear from the time-course of gating current, and from the fact that three procedures that reversibly block INa also block gating current: internal perfusion with Zn2+, prolonged depolarization of the membrane, and inactivation of INa with a short positive prepulse.

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