Luminosity-type Horizontal Cells Research Articles

Modeling the pre- and post-synaptic components involved in the synaptic modification between cones and horizontal cells in carp retina

In retinal synapses between cones and luminosity type horizontal cells (LHC), it was previously found in this laboratory that repetitive red flashes progressively strengthened the LHC's response to red flash, whereas weakened the LHC's response to green flash; repetitive green flash remarkably depressed the LHC's red response, but caused little changes in the cell's green response. However, the detailed mechanisms underlying these phenomena are not entirely clear. In the present study, based on an ion-channel model described mainly in the form of Hodgkin-Huxley equations, possible mechanisms of the short-term synaptic modification are investigated. The simulation results suggest that: (1) the auto-enhancement effect might be induced by the Ca2+-dependent process on the post-synaptic AMPA receptors, which could lead to changes of the ionic channel's properties; (2) the asymmetric response to red- and green-flashes and the mutual-chromatic suppression effects might be attributed to the regulatory effects on the presynaptic glutamate release.

Metabotropic glutamate receptor-mediated hetero-synaptic interaction of red- and green-cone inputs to LHC of carp retina

The role of presynaptic metabotropic glutamate receptor (mGluR) on the interaction of red- and green-cone signals was investigated in luminosity-type horizontal cell (LHC) of isolated carp retina. It was found that a dim red background could enhance LHC’s light response to green stimulus, and a dim green background was also able to increase the cell’s response to red flash. Such mutual color enhancement was eliminated by application of groups II and III mGluR antagonist ( S)-methyl-4-carboxyphenyl-glycine (MCPG). Furthermore, inhibition of glutamate uptake by using d-aspartate ( d-Asp) or dl-threo-β-hydroxy-aspartic acid (THA) completely blocked the mutual enhancement of color signals in LHC. However, the GABAergic feedback pathway in the outer retina was unnecessarily involved.

A competitive model for spectral plasticity in the outer retina

In a previous paper, we reported that repetitive red flashes enhanced the red response of retinal luminosity-type horizontal cell (LHC) and depressed the cell's green response; repetitive green flashes suppressed the cell's red response, but caused trivial changes in its green response. Based on the idea that the spectral plasticity of the horizontal cell may reflect some changes in synaptic efficacy between the horizontal cell and various cones, a simple quantitative model was constructed. The process consists of three components: a linear first-order dynamics, a self-excitatory component within the same kind of synaptic population, and a cross-inhibitory component between different kinds of synaptic populations. It is shown that the model prediction fits reasonably well with the experimental data. The influence of relevant parameters on the model output was further inspected. Our findings suggest that there might be a competitive depression between the red- and green-cone signals that converge onto LHCs.

Differential modulation by AMPA of signals from red- and green-sensitive cones in carp retinal luminosity-type horizontal cells

Intracellular recordings were made from luminosity-type horizontal cells (LHCs) in the isolated superfused carp retina and the effect of AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid), a glutamate receptor agonist, on these cells was studied. AMPA suppressed the responses of LHCs driven by red-sensitive (R-) cones whereas it potentiated the responses driven by green-sensitive (G-) cones. The AMPA effect could be completely blocked by GYKI 53655, a specific AMPA receptor antagonist, indicating the exclusive involvement of AMPA-preferring receptors. The AMPA effect persisted in the presence of picrotoxin (PTX) or dihydrokainic acid (DHK), suggesting that the feedback from LHCs onto cones and glutamate transporters on cones may not be involved. It is suggested that there may exist different AMPA receptor subtypes with distinct characteristics on LHCs, which mediate signal transfer from R-and G-cones to LHCs, respectively.

Structure and function of photoreceptor and second-order cell mosaics in the retina of Xenopus

The structure, physiology, synaptology, and neurochemistry of photoreceptors and second-order (horizontal and bipolar) cells of Xenopus laevis retina is reviewed. Rods represent 53% of the photoreceptors; the majority (97%) are green light-sensitive. Cones belong to large long-wavelength-sensitive (86%), large short-wavelength-sensitive (10%), and miniature ultraviolet wavelength-sensitive (4%) groups. Photoreceptors release glutamate tonically in darkness, hyperpolarize upon light stimulation and their transmitter release decreases. Photoreceptors form ribbon synapses with second-order cells where postsynaptic elements are organized into triads. Their overall adaptational status is regulated by ambient light conditions and set by the extracellular dopamine concentration. The activity of photoreceptors is under circadian control and is independent of the central body clock. Bipolar cell density is about 6000 cells/mm2 They receive mixed inputs from rods and cones. Some bipolar cell types violate the rule of ON-OFF segregation, giving off terminal branches in both sublayers of the inner plexiform layer. The majority of them contain glutamate, a small fraction is GABA-positive and accumulates serotonin. Luminosity-type horizontal cells are more frequent (approximately 1,000 cells/mm2) than chromaticity cells (approximately 450 cells/mm2). The dendritic field size of the latter type was threefold bigger than that of the former. Luminosity cells contact all photoreceptor types, whereas chromatic cells receive their inputs from the short-wavelength-sensitive cones and rods. Luminosity cells are involved in generating depolarizing responses in chromatic horizontal cells by red light stimulation which form multiple synapses with blue-light-sensitive cones. Calculations indicate that convergence ratios in Xenopus are similar to those in central retinal regions of mammals, predicting comparable spatial resolution.

Long-term light history modulates the light response kinetics of luminosity (L)-type horizontal cells in the roach retina

We have examined the effects of prolonged periods of darkness on the responses of luminosity-type horizontal cells (L-HCs) in the freshwater cyprinid, Rutilus rutilus. Two groups of retinae were compared, those recorded after 10 min dark adaptation (SA) and those recorded after 3 h dark adaptation (LA). The results suggest that long-term light history does not modify the general responsiveness of the L-HCs in this species. However, there are apparent changes in the receptive field of the cells and modifications to the kinetics of the light-evoked response. The kinetics changes involve both a delay in the onset of light response and a selective effect on the hyperpolarizing light-ON response. Thus the mean time constant ( τ) for the SA cells was 32.4±2.39 ms ( n=62), whilst that for the LA cells was 53.4±3.03 ms ( n=61). These effects occur in the absence of changes in the relative spectral sensitivity or threshold sensitivity of the HCs. The results suggest that in some vertebrate retinae, prolonged darkness (light-history) may regulate long-term plasticity in the kinetics of the cone–HC pathway.

Stimulus pattern related plasticity of synapses between cones and horizontal cells in carp retina.

Stimulus pattern related synaptic plasticity in the luminosity-type horizontal cell (LHC) of isolated carp retina was investigated. The major findings were: (1) repetitive red flashes progressively strengthened the synaptic connection between red-cone and LHC, whereas weakened that between green-cone and LHC; (2) repetitive green flashes remarkably depressed the LHC's red response, but caused little changes in the cell's green response. A competitive depression between different cone signals is suggested.

UV-sensitive input to horizontal cells in the turtle retina.

Microspectrophotometry, electroretinography and behavioural studies have indicated that ultraviolet (UV) light contributes to functional vision in various vertebrate species. Based on behavioural evidence, this was also suggested for turtle vision. In order to reveal the interactions underlying detection of UV light in the distal retina, we recorded intracellularly the photoresponses of cones and horizontal cells in retinas of Pseudemys scripta elegans and Mauremys caspica and calculated the action spectra of these cells under different conditions of adaptation. In the dark-adapted retina, all three types of horizontal cells; luminosity-type, red/green chromaticity-type and yellow/blue chromaticity-type exhibited increased sensitivity in the UV region of the spectrum. However, chromatic adaptation indicated that only the yellow/blue chromaticity-type horizontal cells received excitatory input from UV-sensitive cones with peak sensitivity approximately 360 nm. The enhanced UV sensitivity of luminosity-type horizontal cells probably reflected the beta-band of the long-wavelength sensitive visual pigment as indicated by the action spectra of dark-adapted L-cones. It is suggested that the enhanced UV sensitivity of red/green chromaticity-type horizontal cells reflects the beta-band of the medium-wavelength sensitive visual pigment. Transmission measurements of the optical media (cornea, lens and vitreous) indicated that UV vision can be functional under normal circumstances.

Dark-suppression and light-sensitization of horizontal cell responses in the hybrid bass retina.

The responsiveness of luminosity-type horizontal cells, recorded intracellularly from isolated hybrid bass retinas, decreased after superfusion for 2 h in constant darkness. Responsiveness was subsequently increased (light-sensitized) up to 10-fold after exposure to several short (approximately 0.5 min) periods of continuous illumination. The increase in horizontal cell responsiveness following light-sensitization was due to an increase of peak response amplitude rather than a reduction of peak response time. The increased responsiveness after light-sensitization was intensity-dependent with brighter sensitizing stimuli causing a greater increase than dimmer stimuli. The extent of LHC dark-suppression was affected by the time of day, being greater when induced during the night than during the day. However, there was no significant difference in horizontal cell responsiveness after light-sensitization in retinas studied during the night compared to those studied during the day. The responsiveness of light-sensitized horizontal cells from isolated hybrid bass retinas was found to be suppressed by relatively brief periods of darkness. The responsiveness of horizontal cells, that were first light-sensitized, decreased by more than 50% following only 5 min of darkness. Suppression of light-sensitized horizontal cell responsiveness after such a short time in the dark has not been described in other teleost retinas. The suppression of light-sensitized horizontal cell responsiveness in hybrid bass retinas may be rapid in comparison to other teleosts.

Short-term effects of dopamine on photoreceptors, luminosity- and chromaticity-horizontal cells in the turtle retina.

The effects of dopamine on luminosity-type horizontal cells have been documented in different vertebrate retinas, both in vivo and in vitro. Some of these effects may reflect direct action of dopamine onto these cells, but indirect effects mediated by presynaptic neurons cannot be ruled out. Furthermore, direct effects of dopamine on horizontal cells may affect other, postsynaptic neurons in the outer plexiform layer. To test these possibilities, we studied the effects of dopamine on photoreceptors and all types of horizontal cells in the turtle (Pseudemys scripta elegans) retina. Receptive-field properties, responsiveness to light, and time course of light responses were monitored with intracellular recordings. Dopamine at a concentration of 40 microM exerted effects with two different time courses. "Short-term" effects were fully developed after 3 min of dopamine application and reversed within 30 min of washout of the drug. "Long-term" effects were fully developed after about 7-10 min and could not be washed out during the course of our experiments. Only the "short-term" effects were studied in detail in this paper. These were expressed in a reduction of the receptive-field size of all types of horizontal cells studied; L1 and L2 luminosity types as well as Red/Green and Yellow/Blue chromaticity types. The L1 horizontal cells did not exhibit signs of reduced responsiveness to light under dopamine, while in the L2 cells and the two types of chromaticity cells responsiveness decreased. None of the rods, long-wavelength-sensitive, or medium-wavelength-sensitive cones exhibited any apparent reduction in their receptive-field sizes or responsiveness to light. The present results suggest that the "short-term" effects of dopamine are not mediated by photoreceptors and are probably due to direct action of dopamine on horizontal cells.

The effects of L-glutamate, AMPA, quisqualate, and kainate on retinal horizontal cells depend on adaptational state: implications for rod- cone interactions

We studied the responses of isolated and intact luminosity-type horizontal cells (L-HC) in the Xenopus retina to L-glutamate (L-glu) and its analogs. Isolated L-HCs studied with whole-cell patch clamp responded to L-glu, kainate (KA), AMPA, or quisqualate (quis) with inward currents from a holding potential of -60 mV, associated with a conductance increase. The current elicited by KA was relatively large and sustained, whereas AMPA or quis evoked a desensitizing current. Coapplication of quis and KA resulted in a smaller current and conductance change than that evoked by a pulse of either alone at the same concentration. This finding suggests that the L-HC has a single subtype of glutamate receptor that responds to both quis and KA. Prior exposure to dopamine enhanced the KA-evoked current about twofold. In the superfused eyecup we found that L-HC responses to quinoxalinediones (CNQX or DNQX) and to L-glu, KA, AMPA, and quis varied as a function of adaptational state. When driven exclusively by either cones or by rods, CNQX/DNQX hyperpolarized the L-HC and reduced its light response, without altering response kinetics, indicating that both rods and cones communicate with L-HCs at ionotropic glutamatergic synapses. Under mesopic conditions, however, as CNQX or DNQX reduced cone input, the rod input to the L-HC increased up to fivefold in magnitude and had slowed kinetics. The depolarizing response of the L-HC to L-glu, AMPA, or quis was relatively small and transient under photopic conditions, but was much larger and sustained when the eyecup was dark adapted. The D1 dopamine antagonist SCH 23390 potentiated the response to quis. In contrast, responses to KA were largest in light-adapted eyecups, were potentiated by a D1 dopamine agonist, SKF 38393, and were reduced by SCH 23390. We hypothesize that the segregated populations of glutamate receptors in the L-HC opposite cone and rod synaptic endings can be separately modulated to respond differentially to the native transmitter, glutamate. In photopic and mesopic states the dominant cone input tonically inhibits rod to L-HC communication. This inhibition appears to occur at the postsynaptic membrane and may be mediated by second messengers.

White noise analysis of a chromatic type horizontal cell in the Xenopus retina.

The dynamics of color-coded signal transmission in the light-adapted Xenopus retina were studied by a combination of white noise (Wiener) analysis and simultaneous recordings from two types of horizontal cells: chromatic-type horizontal cells (C-HCs) are hyperpolarized by blue light and depolarized by red light, whereas luminosity-type horizontal cells (L-HCs) are hyperpolarized by all wave-lengths. The retina was stimulated by two superimposed fields of red and blue light modulated by two independent white noise signals, and the resulting intracellular responses were decomposed into red and blue components (first-order kernels). The first-order kernels predict the intracellular responses with a small degree of error (3.5-9.5% in terms of mean square error) under conditions where modulated responses exceeded 30 mV in amplitude peak-to-peak, thus demonstrating that both red and blue modulation responses are linear. Moreover, there is little or no interaction between the red- and blue-evoked responses; i.e., nearly identical first-order kernels were obtained for one color whether the other color was modulated or not. In C-HCs (but not L-HCs), there were consistent differences in the dynamics of the red and blue responses. In the C-HC, the cutoff frequency of the red response was higher than for the blue (approximately 12 vs 5 Hz), and the red kernel was more bandpass than the blue. In the L-HC, kernel waveform and cutoff frequencies were similar for both colors (approximately 12 Hz or greater), and the time-to-peak of the L-HC kernel was always shorter than either the red or blue C-HC kernel. These results have implications for the mechanisms underlying color coding in the distal retina, and they further suggest that nonlinear phenomena, such as voltage-dependent conductances in HCs, do not contribute to the generation of modulation responses under the experimental conditions used here.

Spectral properties of short-wavelength (blue) cones in the turtle retina

Long- and medium-wavelength cones in the turtle retina participate in complex neural interactions. They are coupled via excitatory pathways to other cones and receive negative feedback inputs from luminosity-type horizontal cells. Little information has been collected on the S- (short-wavelength or blue) cones because they are scarce in the turtle retina and of smaller dimensions compared to the other cone types. In this paper, flash sensitivity action spectra and photoresponses of seven turtle S-cones were measured in the dark-adapted state and during chromatic background illuminations. The desensitizing action of monochromatic background lights was not uniform across the visible spectrum. A red background was most effective in desensitizing the S-cones to long-wavelength stimuli while a blue background light produced its strongest action on the photoresponses elicited by short-wavelength stimuli. The effects of chromatic adaptation on the S-cone action spectrum and on the kinetics of the small-amplitude photoresponses suggested that the S-cones in the turtle retina were involved in complex neural interactions. These included excitatory inputs probably originating in neighboring L-cones and inhibitory long-wavelength inputs probably mediated by L-type horizontal cells.

Effects of background illuminations on the receptive field size of horizontal cells in the turtle retina are mediated by dopamine

Intracellular recordings from luminosity-type horizontal cells of the turtle retina were used to analyze the effects of steady and flickering background illumination on the size of their receptive fields. Both types of background illumination reduce the size of the receptive field to about the same extent. The reduction seems largely due an increase in the coupling resistance between horizontal cells. The effects of both types of background illumination are sensitive to the dopamine antagonist fluphenazine. This suggests that steady and flickering illuminations stimulate the release of endogenous dopamine.

Effects of excitatory amino acids and their antagonists on the light response of luminosity and color-opponent horizontal cells in the turtle (Pseudemys scripta elegans) retina

Both kainic acid (KA) and N-methyl-d-aspartatic acid (NMDA) depolarize luminosity-type horizontal cells (L-type H cells) in normal turtle retina. The presence of both NMDA and non-NMDA receptors for excitatory amino acids (EAAs) on these cells was highlighted by an unusual effect of the noncompetitive NMDA-antagonist, MK-801. In retinas that had been exposed to MK-801, the action of NMDA was irreversibly altered to one of hyperpolarization, while the depolarizing effect of KA was unaltered. The aim of the present study was to further characterize these receptors on L-type H cells and to extend the investigation to color-opponent H cells (C-type H cells). Intracellular recording was used to study the effects of KA, NMDA, MK-801, the competitive NMDA antagonists, 2-amino-5-phosphonopentanoic acid (AP5) and 2-amino-7-phosphonoheptanoic acid (AP7), and the nonspecific EAA antagonist, kynurenic acid (KYN) on the light responses of L-type and C-type H cells in turtle retina. The effects of combinations of these drugs were also studied. In L-type H cells the agonists caused depolarization and loss of light response, KYN caused hyperpolarization and loss of light response, and MK-801, AP5 or AP7 had no direct effect. However, application of NMDA following MK-801, AP5 or AP7, but not KYN, caused hyperpolarization and loss of light response. The depolarizing effect of KA was unaltered by these antagonists. These data confirm the presence of an unusual NMDA receptor on L-type H cells. In the case of red/green C-type H cells, application of KA caused loss of responses to both red and green light, with loss of green responses preceding loss of red responses. NMDA initially removed responses to both red and green light. The most striking effect of NMDA was seen during early washout where the responses to red were reversed (hyperpolarizing). These responses eventually recovered their normal polarity. These results suggest that the depolarizing response of C-type H cells to red light is mediated by L-type H cells, but not via inhibition of the excitatory input from green cones to C-type H cells.

Background and bleaching adaptation in luminosity type horizontal cells in the isolated turtle retina.

1. The effects of background illumination and bleached photopigment on luminosity type horizontal cells were studied in the isolated turtle retina. 2. Background illumination, which produced less than 60% bleaching, hyperpolarized and desensitized the horizontal cells to a degree which depended upon the background intensity. The desensitization of horizontal cells by these backgrounds is described by a Weber-Fechner type relationship. This desensitization primarily reflects the activation of a 'gain reduction' mechanism and cannot be accounted for by 'response compression'. 3. Following the termination of these backgrounds, horizontal cell sensitivity partially recovered but did not return to the pre-background, dark-adapted level. This desensitization was attributed to the presence of bleached photoproducts which were produced by the background exposure. 4. Application of very bright backgrounds caused the horizontal cells to initially hyperpolarize, and then to gradually depolarize towards the dark-adapted level along an exponential time course which appeared to reflect the decreased quantal catching associated with very high levels of photopigment bleaching. 5. From the time constant of the exponential decay of horizontal cell potential during the bright background illumination, the photosensitivity to bleaching of the cone photopigment was determined to be 4.5 x 10(7) effective quanta (633 nm) microns-2. 6. After termination of bright backgrounds which bleached more than 99% of the cone photopigment, the horizontal cell sensitivity increased linearly with time and after 25 min reached a level which was about 15% of the pre-background sensitivity. 7. Bleached photopigment reduces light sensitivity via at least two different mechanisms. For moderate degrees of bleaching (less than 95%), the presence of bleached photoproducts plays the major role in sensitivity control, producing a desensitization which is logarithmically related to the fraction of bleached pigment. During extensive bleaching (greater than 99%), the contribution of reduced quantal catching to sensitivity control becomes apparent and produces an additional loss in sensitivity which is linearly related to the fraction of unbleached pigment present.

A horizontal cell selectively contacts blue-sensitive cones in cyprinid fish retina : intracellular staining with horseradish peroxidase

A horizontal cell selectively contacting blue-sensitive cones has been intracellularly stained with horseradish peroxidase in the retina of a cyprinid fish, the roach. The light microscopical morphology of the cell belonged to the H3 category of horizontal cells found in cyprinid fish retinae. In response to spectral stimuli, the cell generated chromaticity-type S-potentials that were hyperpolarizing to blue and depolarizing to yellow-orange. A red-sensitive hyperpolarizing component was absent possibly because of suppression of the negative feedback pathway between luminosity-type (H1) horizontal cells and green-sensitive cones.

Plasticity of cone horizontal cell functioning in cyprinid fish retina: effects of background illumination of moderate intensity.

In electrophysiological experiments involving intracellular recording from horizontal cells in the isolated retina of the roach, light adaptation of the retina has been shown to result in potentiation both of (1) the depolarizing component of biphasic chromaticity type S-potentials, and (2) the temporal frequency transfer functions of photopic luminosity type horizontal cells. Under identical light adaptation conditions, the number of spinules on horizontal cell dendrites positioned laterally at cone pedicle ribbon synapses, increase by some threefold. The latter effect occurs equally in pedicles of red- and green-sensitive cones. Thus, horizontal cells are 'plastic' in both structural and electrophysiological respects. Furthermore, since the two electrophysiological parameters studied depend on negative feedback from horizontal cells onto cones, the results suggest that it is the inhibitory synapses that are plastic and that spinules may be sites of the negative feedback interaction. Physiological and behavioural aspects of light-dependent horizontal cell plasticity are also discussed.

Decline of blocking effect of cobalt ions on transmission from photoreceptors to horizontal cells during its prolonged application.

In high-Mg2+ medium, luminosity-type cone horizontal cells (L-cells) hyperpolarized and lost their photoresponses at a full membrane hyperpolarization of about -80 mV. These effects of high-Mg2+ are attributed to the blockade of transmitter release from photoreceptors. Application of Co2+ hyperpolarized the L-cells at first and the photoresponses disappeared at full membrane hyperpolarization. After a little while, however, the membrane potential began to depolarize and the light stimuli again evoked responses. The recovery of the membrane potential and photoresponses indicates that prolonged application of Co2+ weakens its ability to block transmission from photoreceptors to L-cells.

GABA transaminase in cyprinid fish retina: Localization and effects of inhibitors on temporal characteristics of S-potentials

Cellular localization and physiology of GABA-transaminase have been studied in the cyprinid fish retina. Immunohistochemical localization of the enzyme in the goldfish retina revealed a broad distribution pattern, including both outer and inner plexiform layers. Well known inhibitors of GABA-transaminase activity, such as gabaculine and ?-vinyl-GABA, caused an improvement of the temporal frequency transfer functions of luminosity type horizontal cells in the roach retina. In contrast, bicuculline had the opposite effect. Results suggest that GABA-transaminase has a physiological role in the retina consistent with the hypothesis that GABAergic (negative) feed-back from horizontal cells to cones regulates the temporal characteristics of light-evoked electrical activity in the outer plexiform layer.