Functional N-methyl-D-aspartate receptors are expressed in cone-driven horizontal cells in carp retina

Glutamate works as a major excitatory neurotransmitter in the vertebrate retina. Whole-cell recordings made from isolated carp cone horizontal cells (H1 cells) showed that N-methyl-D-aspartate (NMDA), co-applied with glycine, induced inward currents that were blocked by the NMDA receptor competitive antagonist D-2-amino-5-phosphonopentanoate (D-AP5) and 5,7-dichlorokynurenic acid (DCKA), a selective NMDA receptor antagonist acting at the glycine site on the NMDA receptor complex. Moreover, calcium imaging showed that NMDA caused a significant elevation of intracellular calcium levels ([Ca(2+)](i)) of H1 cells, which was also blocked by D-AP5. In contrast, neither inward currents nor changes in [Ca(2+)](i) could be induced by NMDA in rod horizontal cells (H4 cells). Intracellular recordings made from H1 cells in the isolated retina, superfused with Ringer's containing 1 mM Mg(2+), in the dark demonstrated that NMDA reduced the light-off overshoot of H1 cells. We therefore conclude that the functional NMDA receptor is expressed in carp H1 cells, from which this receptor has been thought to be absent, and this receptor may play a role in modulating cone-driven signal of horizontal cells in the dark.     

Dynamic model of interaction between cones and horizontal photic cells in the carp retina

A mathematical model is examined of interaction between cones and horizontal L-type cells (HC) in the carp retina using data from intracellular recording of HC spectral response. This model, describing the operation of ionic channels at the membrane of cones and HC, is based on a numerical analog solution to Hodgkin-Huxley differential equations [11] and enables predictions of spectral response levels in HC to be made as a function of time.M. L. Lomonosov State University, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 4, pp. 461–466, July–August, 1989.     

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

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.     

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.     

Lateral feedback from monophasic horizontal cells to cones in carp retina. II. A quantitative model

About half of the monophasic horizontal cells in carp retina receive input from both red- and green-sensitive cones. Since the horizontal cells feed back to cones, the color and feedback pathways result in wavelength- and intensity-dependent changes of the dynamics and of the receptive field amplitude profile of the horizontal cell responses. In this paper we present a quantitative model that describes adequately the color and spatial coding and the dynamics of the responses from monophasic horizontal cells in carp. Lateral feedback plays a distinct role in this model.     

The connectivity of cones and cone horizontal cells in a mosaic-type teleost retina

Summary A total of 20 Golgi-impregnated cone horizontal cells of Nannacara anomala (Cichlidae) were studied in alternating semi- and ultrathin sections in order to examine their connections with the overlying square mosaic of equal double and central single cones. Cone horizontal cells exhibit three types of processes: (a) the long horizontal axon, (b) short horizontal dendrites with a terminal swelling, and (c) cone contacting processes ascending towards the outer plexiform layer. As seen in tangential sections, the latter processes are arranged in the form of two concentric circles including a central spot. The processes of the inner circle contact the eight double cone pedicles of one square unit: processes of the outer circle contact eight more double cone pedicles which are directly adjacent to the square unit. The central spot represents a process which contacts the central single cone. Processes of the inner circle most often terminate in a dichotomous branching which represents the lateral elements to one ribbon synapse, whereas in the outer circle only a single terminal swelling is observed. Because of the mosaic of the cones and the constancy of this pattern of connectivity a model can be constructed where the dendritic fields of the cone horizontal cells overlap to a considerable extent. From this model, it follows that each double cone pedicle is contacted by four different horizontal cells. The functional significance of these findings for color vision is discussed in the light of recent work with the microspectrophotometer characterizing the cone system of this species as bichromatic. The mosaiclike arrangement of the horizontal cell dendrites supports the conclusion that the parallels between the patterns of receptor and horizontal cells are no coincidence but play an important role in lateral inhibition and neural adaptation of the retina.A preliminary report of this study was given at the international symposium Neural principles in vision held at the University of Munich in September 1975Supported by grant Wa 348/1 of the Deutsche Forschungsgemeinschaft     

Light-dependent dynamics of gap junctions between horizontal cells in the retina of the crucian carp

Summary The dynamics of gap junctions between outer horizontal cells or their axon terminals in the retina of the crucian carp were investigated during light and dark adaptation by use of ultrathin-section and freeze-fracture electron microscopy. Light adaptation was induced by red light, while dark adaptation took place under ambient dark conditions. The two principal findings were: (1) The density of connexons within an observed gap junction is high in dark-adapted retina, and low in light-adapted retina. This, respectively, may reflect the coupled and uncoupled state of the gap junction. (2) The size of individual gap junctions is larger in light-than in dark-adapted retinae. Whereas the overall area occupied by gap junctions is reduced with dark adaptation, the percentage of small and very small gap junctions increases dramatically. A lateral shift of connexons in the gap junctional membrane is strongly suggested by these reversible processes of densification and dispersion. Two additional possibilities of gap junction modulation are discussed: (1) the de novo formation of very small gap junctions outside the large ones in the first few minutes of dark adaptation, and (2) the rearrangement of a portion of the very large gap junctions. The idea that the cytoskeleton is involved in such modulatory processes is corroborated by thin-section observations.Dedicated to Professor J. Peiffer on the occasion of his 65th birthday     

Electronic simulation of cones,horizontal cells and bipolar cells of generalized vertebrate cone retina

Electronic analogue of my theoretical model of generalized vertebrate cone retina [Siminoff: J. Theor. Biol. 86, 763 (1980)] is presented. Cone mosaic is simulated by 25x21 grid of phototransistors that have colored filters mounted in front of then to produce red-, green-, and blue-sensitive cones arranged in a trichromatic retina. Each retinal element is simulated by Summator-Integrator and unit gain voltage invertes are used to give correct polarities to output voltages. Dynamic properties of retinal elements are developed solely by temporal interplay of antagonistic input voltages with differing time courses, and spatial organization of receptive fields is developed by unit hexagons that precisely define cone input voltages to subsequent elements. Electronic model contains both color- and non-colorcoded channels. Negative feedback from L-horizontal cells to cones, electrical coupling of like-cones, and electrical coupling of like-horizontal cells are simulated by feedfoward circuits. Stray light is present due to light scattering properties of colored filters used to simulate color selectivety of cones. Stationary and moving spots of white and colored lights of varied sizes and intensities are used to study characteristics of electronic analogue. Results demonstrate practicality of electronic simulation to function analogous to real cone retinas to process visual stimuli and give information to higher centers as to size, shape, color and motion of objects in visual world.     

Modelling the effects of a negative feedback circuit from horizontal cells to cones on the impulse responses of cones and horizontal cells in the catfish retina

A model of the cone-L-HC circuit for the catfish retina is presented with the following features: the outer segment consists of a compression factor and 7 low-pass filters in tandem; the cone pedicle consists of an internal negative feedback circuit in series with a low-pass filter; and the L-HC consists of a low-pass filter and forms a negative feedback circuit with the cone pedicle. By proper adjustment of the various time constants of the low-pass filters and the gain factors, the impulse responses for cones and L-HCs of the catfish retina (and turtle) can be duplicated. The negative feedback gain increases with increasing levels of mean illuminance which causes the monophasic impulse responses to become faster, biphasic and decrease in amplitude, i.e. in gain. This is an expression of the Weber-Fechner law.     

Interaction between horizontal cells of the turtle retina

Interaction between horizontal cells of the turtle retina was studied by two microelectrodes (polarizing and recording), inserted into different cells at different distances apart. The presence of a direct electrical connection was demonstrated between the L cells of the same type (I, with large, and II, with small receptive fields). Its magnitude depends on the conditions of illumination and the level of the membrane potential, possibly because of the properties of the subsynaptic and nonsynaptic membranes of the horizontal cells. No direct electrical connection exists between L cells of different types. However, hyperpolarization of the type I cells through the microelectrode or by stimulation with a circle of light evoked depolarization in the type II cells. This indirect connection between the horizontal cells, also dependent on the conditions of illumination, can probably be explained by feedback to these cells from the photoreceptors. Polarization of L cells of both types had no effect on horizontal cells of color type.     

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 (α-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.     

Interactions leading to colour opponency in ganglion cells of the turtle retina

In the turtle retina, colour-dependent photoresponses could be recorded intracellularly from ganglion cells receiving only bipolar cell input. Thus, the mechanism for colour discrimination by these ganglion cells (type A) is contained in the outer plexiform layer of the retina and depends on interaction between horizontal and cone cells. Ganglion cells receiving an additional amacrine input (type B) are not influenced by colour, and have about 0.7 logarithmic unit lower absolute sensitivity to peak wavelength than have type A ganglion cells.     

Modulation of synaptic transfer between retinal cones and horizontal cells by spatial contrast

We studied the influence of steady annular light on the kinetics and sensitivity of horizontal cell (HC) responses to modulation of the intensity of small concentric spots in the turtle retina. As shown by previous investigators, when the intensity of the annulus was equal to the mean spot intensity, spot response kinetics were the same as those for the modulation of spatially uniform light. Turning off the annulus attenuated dramatically high-frequency flicker sensitivity and enhanced somewhat low-frequency sensitivity. This phenomenon reflects a modulation of synaptic transfer between cones and second-order neurons that is mediated by cones, and it will be referred to as cone-mediated surround enhancement (CMSE). Our main results are as follows: (a) The change in test-spot response sensitivity and kinetics upon dimming a steady surrounding annulus is a consequence of the change in spatial contrast rather than change in overall light level. (b) Introduction of moderate contrast between the mean spot intensity and steady surrounding light intensity causes a marked change in spot response kinetics. (c) The dependence of spot response kinetics on surrounding light can be described by a phenomenological model in which the steady state gain and the time constant of one or two single-stage, low-pass filters increase with decreasing annular light intensity (d) The effect of surrounding light on spot responses of a given HC is not determined by change in the steady component of the membrane potential of that cell. (e) Light outside the receptive field of an HC can affect that cell's spot response kinetics. (f) In an expanding annulus experiment, the distance over which steady annular light affects spot response kinetics varies among HCs and can be quite different even between two cells with closely matched receptive field sizes. (g) The degree of CMSE is correlated with HC receptive field size. This correlation suggests that part of the enhancement mechanism is located in the HC. Taken together, our results suggest the involvement of the inner retina in CMSE.     

Strongly pH-buffered ringer's solution expands the receptive field size of horizontal cells in the carp retina

By intracellular recordings, we studied the effects of pH buffering on the size of the receptive field and the extent of dye coupling of horizontal cells (HCs) in the light-adapted carp retina. These parameters were compared between data obtained in fortified Ringer's solution and those obtained in control bicarbonate Ringer's of the same pH (7.60). In Ringer's fortified with 10 mM HEPES or 15 mM Tris, the dye-coupling ratio of HCs increased by 71% and 70%, respectively. These fortified Ringer's solutions also depolarized the dark membrane potential and increased the light-evoked response. The HC receptive field profile could be described by the exponential decline in peak response amplitude to a slit of light moved tangentially from the recording electrode. Thus, the receptive field size was determined as a space constant proportional to (gj/gm)(1/2), where gj and gm denote gap and non-gap-junctional conductances. The HEPES- or Tris-fortified Ringer's significantly increased the space constant by 43% and 41%, respectively. Since dye coupling was increased in the fortified Ringer's, it is likely that gj increased more than gm as a result of alkalinization of the cytosol. Since HEPES has an aminosulfonate moiety, it has been assumed to close the hemi-channels of connexin 26, but the pH-buffering effects were essentially the same as those of Tris that has no aminosulfonate moiety. Therefore, it is unlikely that the closure of connexin 26 hemichannels is responsible for the change in the receptive field size of HCs.     

突触后钙通路有助于视锥与L型水平细胞间的突触可塑性

我们实验室以前发现,视网膜视锥与亮度型水平细胞（luminosity—type horizontal cell,LHC）之间的突触传递效率具有可塑性。重复性刺激红敏视锥增加了LHC对红光的超极化反应幅度,而且这种增强作用是可逆的。在本文中,我们运用细胞内记录技术和药理学分析的方法来考察重复性红光刺激引起的反应增强的可能机制。当通过胞内注射Ca^2＋的螯合剂EGTA来降低LHC内的Ca^2＋浓度后,重复性红光引起的反应增强被抑制,提示突触后钙信号是反应增强的一个重要因素。另外,反应增强现象还可以被钙离子通透的AMPA受体（Ca^2＋-permeable AMPA receptor,CP-AMPAR）的拈抗剂阻断,说明通过钙离子通透的谷氨酸受体内流的Ca^2＋与胞内Ca^2＋浓度的改变有关。进一步发现,胞外灌流ryanodine或caffeine也可以消除反应增强现象,说明由钙诱导的钙释放（calcium—induced calcium release,CICR）引起的钙信号可能也参与了反应增强现象的产生。结果提示,CICR和CP—AMPAR与重复性红光刺激引起的LHC对红光的反应增强有关。     

Displaced horizontal cells in the chick retina

The retina of the chick contains retinal cells of a morphology very similar to that of the horizontal cells, but the perikarya, axons, and axon terminals lie in the inner plexiform layer. The discovery of this neuronal ectopia appears to support the idea that some horizontal and amacrine cells derive from a common, freely migrating cell.