Bifurcation analysis of nonlinear retinal horizontal cell models. II. Network properties

1990 ◽  
Vol 64 (1) ◽  
pp. 248-261 ◽  
Author(s):  
R. L. Winslow ◽  
S. Ma
Keyword(s):  
Horizontal Cell ◽  
Membrane Currents ◽  
Horizontal Cells ◽  
Synaptic Conductance ◽  
Cell Models ◽  
Voltage Dependent ◽  
Full Complement ◽  
Network Properties ◽  
Light Stimuli ◽  
Coupling Conductance

1. We have previously presented a model of horizontal-cell soma isolated from fish retina. The model consists of a synaptic conductance representing input from photoreceptors in parallel with voltage-dependent membrane currents. Membrane-current models are based on I-V curves measured in isolated fish horizontal cells. Bifurcation theory was used to analyze model properties. The major findings of this study were 1) the inward Ca2+ current must be inactivated to account for horizontal-cell resting potentials and hyperpolarizing responses to light stimuli in a background of dark, and 2) the synaptic conductance controls the bifurcation structure of the model, with bistable behavior occurring at small and monostable behavior occurring at larger values of the synaptic conductance. The synaptic conductance at the point of transition from bistable to monostable behavior corresponds to the activation of as few as 100 synaptic channels. Thus tonic synaptic input from photoreceptors and inactivation of the inward Ca2+ current act to “linearize” responses of isolated horizontal-cell models. 2. The model described in this paper extends these analyses to large networks of horizontal cells in which each cell is coupled resistively to its nearest neighbors and is modeled with the use of the full complement of nonlinear membrane currents. Network responses to arbitrary patterns of conductance change (simulating inputs from photoreceptors), current-, or voltage-clamp stimuli are computed using the Newton iteration. The Newton descent direction is computed using either conjugate gradient (CG) or preconditioned CG algorithms. 3. An analysis of network stability properties is performed. Network I-V curves are computed by voltage-clamping the center node and computing the current required to maintain the clamp voltage. Computations are performed on networks of model cells in which the Ca2+ current is fully activated and the synaptic conductance is zero, thus making each cell as nonlinear as possible. Coupling conductance values slightly greater than 100 pS provide a current shunt sufficient to prevent the generation of Ca2+ action potentials in the network. This coupling conductance corresponds to the conductance of as few as two gap-junction channels and is more than two orders of magnitude less than the coupling known to exist between pairs of cultured horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Postsynaptic Response Kinetics Are Controlled by a Glutamate Transporter at Cone Photoreceptors

1998 ◽  
Vol 79 (1) ◽  
pp. 190-196 ◽  
Author(s):  
Lubor Gaal ◽  
Botond Roska ◽  
Serge A. Picaud ◽  
Samuel M. Wu ◽  
Robert Marc ◽  
...  
Keyword(s):  
Voltage Dependence ◽  
Light Flash ◽  
Horizontal Cell ◽  
Glutamate Transporter ◽  
Light Response ◽  
Horizontal Cells ◽  
Cone Photoreceptors ◽  
Postsynaptic Response ◽  
Glutamate Concentration ◽  
Voltage Dependent

Gaal, Lubor, Botond Roska, Serge A. Picaud, Samuel M. Wu, Robert Marc, and Frank S. Werblin. Postsynaptic response kinetics are controlled by a glutamate transporter at cone photoreceptors. J. Neurophysiol. 79: 190–196, 1998. We evaluated the role of the sodium/glutamate transporter at the synaptic terminals of cone photoreceptors in controlling postsynaptic response kinetics. The strategy was to measure the changes in horizontal cell response rate induced by blocking transporter uptake in cones with dihydrokainate (DHK). DHK was chosen as the uptake blocker because, as we show through autoradiographic uptake measurements, DHK specifically blocked uptake in cones without affecting uptake in Mueller cells. Horizontal cells depolarized from about −70 to −20 mV as the exogenous glutamate concentration was increased from ∼1 to 40 μM, so horizontal cells can serve as “glutamate electrodes” during the light response. DHK slowed the rate of hyperpolarization of the horizontal cells in a dose-dependent way, but didn't affect the kinetics of the cone responses. At 300 μM DHK, the rate of the horizontal cell hyperpolarization was slowed to only 17 ± 8.5% (mean ± SD) of control. Translating this to changes in glutamate concentration using the slice dose response curve as calibration in Fig. 2 , DHK reduced the rate of removal of glutamate from ∼0.12 to 0.031 μM/s. The voltage dependence of uptake rate in the transporter alone was capable of modulating glutamate concentration: we blocked vesicular released glutamate with bathed 20 mM Mg2+ and then added 30 μM glutamate to the bath to reestablish a physiological glutamate concentration level at the synapse and thereby depolarize the horizontal cells. Under these conditions, a light flash elicited a 17-mV hyperpolarization in the horizontal cells. When we substituted kainate, which is not transported, for glutamate, horizontal cells were depolarized but light did not elicit any response, indicating that the transporter alone was responsible for the removal of glutamate under these conditions. This suggests that the transporter was both voltage dependent and robust enough to modulate glutamate concentration. The transporter must be at least as effective as diffusion in removing glutamate from the synapse because there is only a very small light response once the transporter is blocked. The transporter, via its voltage dependence on cone membrane potential, appears to contribute significantly to the control of postsynaptic response kinetics.[Figure: see text]

Electrical coupling of retinal horizontal cells mediated by distinct voltage-independent junctions

1999 ◽  
Vol 16 (5) ◽  
pp. 811-818 ◽  
Author(s):  
CHENGBIAO LU ◽  
DAO-QI ZHANG ◽  
DOUGLAS G. McMAHON
Keyword(s):  
Single Channel ◽  
Lucifer Yellow ◽  
Horizontal Cell ◽  
Electrical Coupling ◽  
Cell Voltage ◽  
Horizontal Cells ◽  
Simultaneous Application ◽  
Dependent Inactivation ◽  
Cellular Junctions ◽  
Voltage Dependent

Electrical coupling between H2 horizontal cell pairs isolated from the hybrid bass retina was studied using dual whole-cell, voltage-clamp technique. Voltage-dependent inactivation of junctional currents in response to steps in transjunctional voltage (Vj) over a range of ±100 mV was characterized for 89 cell pairs. Approximately one-quarter of the pairs exhibited strongly voltage-dependent junctions (>50% reduction in junctional current at ±100 mV), another quarter of the pairs exhibited voltage-independent junctional current (<5% reduction at ±100 mV), and the remainder of the pairs exhibited intermediate values for voltage inactivation. We focused on further characterizing the Vj-independent junctions of horizontal cells, which have not been described previously in detail. When Lucifer Yellow dye was included in one recording pipette, pairs exhibiting Vj-independent coupling showed no (9/12), or limited (3/12), passage of dye. Vj-independent coupling was markedly less sensitive to the modulators SNP (100–300 μM, −9% reduction in coupling) and dopamine (100–300 μM, −6%) than were Vj-dependent junctions (−45% and −44%). However, simultaneous application of both SNP and dopamine significantly reduced Vj-independent coupling (−56%). Both Vj-independent and Vj-dependent junctions were blocked by DMSO (1–2%), but Vj-independent junctions were not blocked by heptanol. Single-channel junctional conductances of Vj-independent junctions range from 112–180 pS, versus 50–60 pS for Vj-dependent junctions. The results reveal that Vj-independent coupling in a subpopulation of horizontal cells from the hybrid bass retina is mediated by cellular junctions with physiological and pharmacological characteristics distinct from those previously described in fish horizontal cells.

scholarly journals Dopamine modulates in a differential fashion T- and L-type calcium currents in bass retinal horizontal cells.

1993 ◽  
Vol 102 (2) ◽  
pp. 277-294 ◽  
Author(s):  
C Pfeiffer-Linn ◽  
E M Lasater
Keyword(s):  
Cyclic Amp ◽  
Calcium Channels ◽  
Calcium Current ◽  
Horizontal Cell ◽  
Calcium Currents ◽  
Horizontal Cells ◽  
White Bass ◽  
Cell Calcium ◽  
Cone Type ◽  
Voltage Dependent

White bass (Roccus chrysops) retinal horizontal cells possess two types of voltage-activated calcium currents which have recently been characterized with regard to their voltage dependence and pharmacology (Sullivan, J., and E. M. Lasater. 1992. Journal of General Physiology. 99:85-107). A low voltage-activated transient current was identified which resembles the T-type calcium current described in a number of other preparations, along with a sustained high threshold, long-lasting calcium current that resembles the L-type calcium current. Here we report on the modulation of horizontal cell calcium channels by dopamine. Under whole-cell voltage clamp conditions favoring the expression of both calcium currents, dopamine had opposing actions on the two types of voltage-sensitive calcium currents in the same cone-type horizontal cell. The L-type calcium current was significantly potentiated by dopamine while the T-type current was simultaneously reduced. Dopamine had no effect on calcium currents in rod-type horizontal cells. Both of dopamine's actions were mimicked with the D1 receptor agonist, SKF 38393, and blocked by application of the D1 specific antagonist, SCH 23390. Dopamine's actions on the two types of calcium currents in white bass horizontal cells are mimicked by the cell membrane-permeant cyclic AMP derivative, 8-(4-chlorophenylthio)-cyclic AMP, suggesting that dopamine's action is linked to a cAMP-mediated second messenger system. Furthermore, the inhibitor of cAMP-dependent protein kinase blocked both of dopamine's actions on the voltage-dependent calcium channels when introduced through the patch pipette. This indicates that protein phosphorylation is involved in modulating horizontal cell calcium channels by dopamine. Taken together, these results show that dopamine has differential effects on the voltage-dependent calcium currents in retinal horizontal cells. The modulation of these currents may play a role in shaping the response properties of horizontal cells.

Membrane currents of horizontal cells isolated from turtle retina

1992 ◽  
Vol 68 (2) ◽  
pp. 351-361 ◽  
Author(s):  
A. Golard ◽  
P. Witkovsky ◽  
D. Tranchina
Keyword(s):  
Patch Clamp ◽  
Bessel Function ◽  
Cell Body ◽  
Axon Terminal ◽  
Horizontal Cell ◽  
Membrane Currents ◽  
Horizontal Cells ◽  
Signal Transfer ◽  
Axon Terminals ◽  
Space Constant

1. Membrane currents of horizontal cells isolated from the retina of the turtle, Pseudemys, were characterized by the whole-cell patch-clamp technique. 2. Four membrane currents were identified: an anomalous rectifier blocked by barium, a transient A-current, a sustained L-type calcium current enhanced by Bay K 8644, and a fast, tetrodotoxin-sensitive sodium current. Each of these four currents was found in both horizontal cell somata and axon terminals. 3. The current-voltage relations of axon terminals and somata were similar, but, in the normal operating range of the cell (-30 to -50 mV), the mean slope resistance of the axon terminal was higher (1.38 G omega) than that of the soma (0.26 G omega). 4. Exposure to either glutamate, kainate, or quisqualate induced a sustained inward current in horizontal cell axon terminals. The reversal potential for this current was -3 mV when tested with voltage steps and +9.1 mV when measured by a voltage ramp. The same horizontal cells were insensitive to N-methyl-D-aspartate. 5. A continuum model was developed to compute the degree of signal transfer between a horizontal cell body and its axon terminal. The model consisted of a network of electrically coupled somata that communicates with a network of electrically coupled axon terminals through the connecting axons. The specific membrane resistances used for the model derived from the patch-clamp measures. 6. We computed the voltage change elicited in either the layer of somata or of axon terminals by a static light stimulus of arbitrary dimensions. The amplitude of a spot response as a function of its radius was given by the weighted sum of two Bessel functions with different space constants. 7. The computed responses of the cell body were dominated by the Bessel function with the smaller space constant, whereas those of the axon terminal depended primarily on the Bessel function with the larger space constant. 8. The model predicts that, in contrast to the findings in teleost retina, there is little signal transfer between the somata and axon terminals of horizontal cell in the turtle retina.

Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina

1992 ◽  
Vol 68 (4) ◽  
pp. 1143-1150 ◽  
Author(s):  
Y. Ueda ◽  
A. Kaneko ◽  
M. Kaneda
Keyword(s):  
Potassium Current ◽  
Horizontal Cell ◽  
Potassium Currents ◽  
Ionic Currents ◽  
Horizontal Cells ◽  
Membrane Properties ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Cat Retina ◽  
Voltage Dependent

1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Spectral Responses in Zebrafish Horizontal Cells Include a Tetraphasic Response and a Novel UV-Dominated Triphasic Response

2010 ◽  
Vol 104 (5) ◽  
pp. 2407-2422 ◽  
Author(s):  
Victoria P. Connaughton ◽  
Ralph Nelson
Keyword(s):  
Genetic Model ◽  
Horizontal Cell ◽  
Cell Voltage ◽  
Horizontal Cells ◽  
Color Processing ◽  
Light Stimuli ◽  
Absorbance Peak ◽  
Uv Cone ◽  
L1 And L2 ◽  
Spectral Responses

Zebrafish are tetrachromats with red (R, 570 nm), green (G, 480 nm), blue (B, 415 nm), and UV (U, 362 nm) cones. Although neurons in other cyprinid retinas are rich in color processing neural circuitry, spectral responses of individual neurons in zebrafish retina, a genetic model for vertebrate color vision, are yet to be studied. Using dye-filled sharp microelectrodes, horizontal cell voltage responses to light stimuli of different wavelengths and irradiances were recorded in a superfused eyecup. Spectral properties were assessed both qualitatively and quantitatively. Six spectral classes of horizontal cell were distinguished. Two monophasic response types (L1 and L2) hyperpolarized at all wavelengths. L1 sensitivities peaked at 493 nm, near the G cone absorbance maximum. Modeled spectra suggest equally weighted inputs from both R and G cones and, in addition, a “hidden opponency” from blue cones. These were classified as R−/G−/(b+). L2 sensitivities were maximal at 563 nm near the R cone absorbance peak; modeled spectra were dominated by R cones, with lesser G cone contributions. B and UV cone signals were small or absent. These are R−/g−. Four chromatic (C-type) horizontal cells were either depolarized (+) or hyperpolarized (−) depending on stimulus wavelength. These types are biphasic (R+/G−/B−) with peak excitation at 467 nm, between G and B cone absorbance peaks, UV triphasic (r−/G+/U−) with peak excitation at 362 nm similar to UV cones, and blue triphasic (r−/G+/B−/u−) and blue tetraphasic (r−/G+/B−/u+), with peak excitation at 409 and 411 nm, respectively, similar to B cones. UV triphasic and blue tetraphasic horizontal cell spectral responses are unique and were not anticipated in previous models of distal color circuitry in cyprinids.

scholarly journals Synaptic Scaffolds, Ion Channels and Polyamines in Mouse Photoreceptor Synapses: Anatomy of a Signaling Complex

2021 ◽  
Vol 15 ◽  
Author(s):  
Alejandro Vila ◽  
Eyad Shihabeddin ◽  
Zhijing Zhang ◽  
Abirami Santhanam ◽  
Christophe P. Ribelayga ◽  
...  
Keyword(s):  
Ion Channels ◽  
Horizontal Cell ◽  
Plexiform Layer ◽  
Horizontal Cells ◽  
Mouse Retina ◽  
Pannexin 1 ◽  
Signaling Complex ◽  
Voltage Dependent ◽  
Polyamine Content ◽  
And Control

Synaptic signaling complexes are held together by scaffold proteins, each of which is selectively capable of interacting with a number of other proteins. In previous studies of rabbit retina, we found Synapse-Associated Protein-102 (SAP102) and Channel Associated Protein of Synapse-110 (Chapsyn110) selectively localized in the tips of horizontal cell processes at contacts with rod and cone photoreceptors, along with several interacting ion channels. We have examined the equivalent suites of proteins in mouse retina and found similarities and differences. In the mouse retina we identified Chapsyn110 as the scaffold selectively localized in the tips of horizontal cells contacting photoreceptors, with Sap102 more diffusely present. As in rabbit, the inward rectifier potassium channel Kir2.1 was present with Chapsyn110 on the tips of horizontal cell dendrites within photoreceptor invaginations, where it could provide a hyperpolarization-activated current that could contribute to ephaptic signaling in the photoreceptor synapses. Pannexin 1 and Pannexin 2, thought to play a role in ephaptic and/or pH mediated signaling, were present in the outer plexiform layer, but likely not in the horizontal cells. Polyamines regulate many ion channels and control the degree of rectification of Kir2.1 by imposing a voltage-dependent block. During the day polyamine immunolabeling was unexpectedly high in photoreceptor terminals compared to other areas of the retina. This content was significantly lower at night, when polyamine content was predominantly in Müller glia, indicating daily rhythms of polyamine content. Both rod and cone terminals displayed the same rhythm. While polyamine content was not prominent in horizontal cells, if polyamines are released, they may regulate the activity of Kir2.1 channels located in the tips of HCs. The rhythmic change in polyamine content of photoreceptor terminals suggests that a daily rhythm tunes the behavior of suites of ion channels within the photoreceptor synapses.

scholarly journals Lateral feedback from monophasic horizontal cells to cones in carp retina. I. Experiments.

1989 ◽  
Vol 93 (4) ◽  
pp. 681-694 ◽  
Author(s):  
M Kamermans ◽  
B W van Dijk ◽  
H Spekreijse ◽  
R C Zweypfenning
Keyword(s):  
Horizontal Cell ◽  
Horizontal Cells ◽  
Color Coding ◽  
Cell Adaptation ◽  
Test Spot ◽  
Displacement Experiments ◽  
High Stimulus ◽  
Integration Area

The spatial and color coding of the monophasic horizontal cells were studied in light- and dark-adapted retinae. Slit displacement experiments revealed differences in integration area for the different cone inputs of the monophasic horizontal cells. The integration area measured with a 670-nm stimulus was larger than that measured with a 570-nm stimulus. Experiments in which the diameter of the test spot was varied, however, revealed at high stimulus intensities a larger summation area for 520-nm stimuli than for 670-nm stimuli. The reverse was found for low stimulus intensities. To investigate whether these differences were due to interaction between the various cone inputs to the monophasic horizontal cell, adaptation experiments were performed. It was found that the various cone inputs were not independent. Finally, some mechanisms for the spatial and color coding will be discussed.

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.

Nitric oxide and cGMP modulate retinal glutamate receptors

1996 ◽  
Vol 76 (4) ◽  
pp. 2307-2315 ◽  
Author(s):  
D. G. McMahon ◽  
L. V. Ponomareva
Keyword(s):  
Nitric Oxide ◽  
Glutamate Receptors ◽  
Horizontal Cell ◽  
Synaptic Function ◽  
Horizontal Cells ◽  
Glutamate Excitotoxicity ◽  
No Donors ◽  
Receptor Modulation ◽  
Cell Recording ◽  
Endogenous Nitric Oxide

1. In the retina, as in other regions of the vertebrate central nervous system, glutamate receptors mediate excitatory chemical synaptic transmission and are a critical site for the regulation of cellular communication. In this study, retinal horizontal cells from the hybrid less were dissociated in cell culture, voltage clamped by the whole cell recording technique, and the currents evoked by application of excitatory amino acids recorded. 2. Responses to glutamate and its agonist kainate were reduced by approximately 50% in the presence of the nitric oxide (NO) donors sodium nitroprusside and S-nitroso-N-acetylpenicillamine. The effect of these compounds was blocked by the NO scavenger hemoglobin. 3. This effect of NO donors on kainate currents could be mimicked by the application of a membrane permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-Br-cGMP. The NO effect was also blocked by application of the guanylate cyclase inhibitor LY-83583, and by a protein kinase G inhibitor peptide. 4. In H1-type horizontal cells, stimulation of endogenous nitric oxide synthase with L-arginine reduced kainate responses, whereas application of D-arginine had no effect. 5. This receptor modulation mechanism may act in concert with other pre- and postsynaptic mechanisms to modify horizontal cell synaptic function according to the adaptational state of the retina and also may protect horizontal cells from glutamate excitotoxicity.

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