Receptive field mechanisms of ganglion cells in the cat retina

On the basis of anatomical and physiological results of the vertebrate retina, a method is proposed for analysing the respective fields of ganglion cells in the cat retina. In the model, we assume the following: (a) Ganglion cells receive their input from bipolar and/or amacrine cells. (b) The nonlinearity of ganglion cell responses is due to the activities of transient type amacrine cells. The method has been proved to be effective. According to the results of this investigation, the receptive field properties of X type and Y type ganglion cells are heterogeneous. Thus, it may be considered that their receptive fields consist of center and surround mechanisms. The receptive field properties of X-cells are almost linear and the X-cells seem to receive most of their input from bipolar cells. On the other hand, the ones of Y-cells are highly nonlinear. Consequently, it is conceivable that the Y-cells receive their input mainly from transient type amacrine cells.     

Receptive field mechanisms of cat X and Y retinal ganglion cells

We investigated receptive field properties of cat retinal ganglion cells with visual stimuli which were sinusoidal spatial gratings amplitude modulated in time by a sum of sinusoids. Neural responses were analyzed into the Fourier components at the input frequencies and the components at sum and difference frequencies. The first-order frequency response of X cells had a marked spatial phase and spatial frequency dependence which could be explained in terms of linear interactions between center and surround mechanisms in the receptive field. The second-order frequency response of X cells was much smaller than the first-order frequency response at all spatial frequencies. The spatial phase and spatial frequency dependence of the first-order frequency response in Y cells in some ways resembled that of X cells. However, the Y first-order response declined to zero at a much lower spatial frequency than in X cells. Furthermore, the second-order frequency response was larger in Y cells; the second-order frequency components became the dominant part of the response for patterns of high spatial frequency. This implies that the receptive field center and surround mechanisms are physiologically quite different in Y cells from those in X cells, and that the Y cells also receive excitatory drive from an additional nonlinear receptive field mechanism.     

The effect of strychnine, bicuculline, and picrotoxin on X and Y cells in the cat retina

The effect of intravenous strychnine and the GABA antagonists picrotoxin and bicuculline upon the discharge pattern of center-surround-organized cat retinal ganglion cells of X and Y type were studied. Stimuli (mostly scotopic, and some photopic) were selected such that responses from both on and off-center cells were either due to the center, due to the surround, or clearly mixed. Pre-drug control responses were obtained, and their behavior following administration of the antagonists was observed for periods up to several hours. X-cell responses were affected in a consistent manner by strychnine while being unaffected by GABA antagonists. All observed changes following strychnine were consistent with a shift in center-surround balance of X cells in favor of the center. For Y-cell responses to flashing annuli following strychnine, there was either no shift or a relatively small shift in center-surround balance. Compared to X-cell responses to flashing lights, those of Y cells were very little affected by strychnine and in most cases were unaffected. It thus appears that glycine plays a similar role in receptive field organization of X cells as does GABA in Y cells (Kirby and Enroth-Cugell, 1976. J. Gen. Physiol. 68:465-484).     

A spatio-temporal model of ganglion cell receptive field in the cat retina

A spatio-temporal model of ganglion cell receptive fields is proposed on the basis of receptive field characteristics of cat retinal ganglion cells reported in our previous paper. The model consists of the linear and nonlinear mechanisms in the ganglion cell receptive field. The linear mechanism is assumed to be composed of antagonistic center and surround mechanisms. Then, by integrating these mechanisms we construct a spatio-temporal impulse response function of ganglion cell receptive field. Here we assume that spatio-temporal impulse response function may be factored into spatial and temporal terms. By Fouriertransforming the spatio-temporal impulse response function, we can obtain the spatio-temporal transfer function. Contrast sensitivity characteristics of X-and Y-cells in the cat retina may be explained by the transfer function.     

Gap junctions with amacrine cells provide a feedback pathway for ganglion cells within the retina.

In primates, one type of retinal ganglion cell, the parasol cell, makes gap junctions with amacrine cells, the inhibitory, local circuit neurons. To study the effects of these gap junctions, we developed a linear, mathematical model of the retinal circuitry providing input to parasol cells. Electrophysiological studies have indicated that gap junctions do not enlarge the receptive field centres of parasol cells, but our results suggest that they make other contributions to their light responses. According to our model, the coupled amacrine cells enhance the responses of parasol cells to luminance contrast by disinhibition. We also show how a mixed chemical and electrical synapse between two sets of amacrine cells presynaptic to the parasol cells might make the responses of parasol cells more transient and, therefore, more sensitive to motion. Finally, we show how coupling via amacrine cells can synchronize the firing of parasol cells. An action potential in a model parasol cell can excite neighbouring parasol cells, but only when the coupled amacrine cells also fire action potentials. Passive conduction was ineffective due to low-pass temporal filtering. Inhibition from the axons of the coupled amacrine cells also produced oscillations that might synchronize the firing of more distant ganglion cells.     

Morphological identification of on- and off-centre brisk transient (Y) cells in the cat retina

Brisk transient (Y) cells were recorded extracellularly in the cat retina. The position and shape of their receptive field centres were plotted on a tangent screen, together with retinal landmarks, such as blood vessels adjacent to the recording area. After recording the retina was processed as a whole mount and stained with a reduced-silver method (see appendix). This technique stains the entire alpha cell population including the dendritic trees. Alpha cells are the morphological correlate of the brisk transient cells (Boycott & W?ssle 1974; Cleland et al. 1975). Maps of the screen plot and the histological preparation could be accurately superimposed by means of the retinal landmarks and each recorded brisk transient unit could unequivocally be attributed to a particular alpha cell. Alpha cell dendritic trees are unistratified in either of two laminae within the inner plexiform layer: (1) close to the inner nuclear layer border, 'outer alpha cells', or (2) about 10 micrometers further towards the ganglion cell layer, 'inner alpha cells'. This stratification difference can be observed in whole mounts for large populations of cells (W?ssle et al. 1981). Of the recorded brisk transient cells, all on-centre units were inner alphas and all off-centre units outer alphas.     

On the complex dynamics of intracellular ganglion cell light responses in the cat retina

We recorded intracellular responses from cat retinal ganglion cells to sinusoidal flickering lights, and compared the response dynamics with a theoretical model based on coupled nonlinear oscillators. Flicker responses for several different spot sizes were separated in a smooth generator (G) potential and corresponding spike trains. We have previously shown that the G-potential reveals complex, stimulus-dependent, oscillatory behavior in response to sinusoidally flickering lights. Such behavior could be simulated by a modified van der Pol oscillator. In this paper, we extend the model to account for spike generation as well, by including extended Hodgkin-Huxley equations describing local membrane properties. We quantified spike responses by several parameters describing the mean and standard deviation of spike burst duration, timing (phase shift) of bursts, and the number of spikes in a burst. The dependence of these response parameters on stimulus frequency and spot size could be reproduced in great detail by coupling the van der Pol oscillator and Hodgkin-Huxley equations. The model mimics many experimentally observed response patterns, including non-phase-locked irregular oscillations. Our findings suggest that the information in the ganglion cell spike train reflects both intraretinal processing, simulated by the van der Pol oscillator, and local membrane properties described by Hodgkin-Huxley equations. The interplay between these complex processes can be simulated by changing the coupling coefficients between the two oscillators. Our simulations therefore show that irregularities in spike trains, which normally are considered to be noise, may be interpreted as complex oscillations that might carry information.To the memory of Prof. Otto-Joachim Grusser     

Immunohistochemical localization of GABAA receptors in the scotopic pathway of the cat retina

The distribution of GABA_A receptors in the inner plexiform layer of cat retina was studied using monoclonal antibodies against the 2/3 subunits. A dense band of receptor labeling was found in the inner region of the inner plexiform layer where the rod bipolar axons terminate. Three forms of evidence indicate that the GABA_A receptor labeling is on the indoleamine-accumulating, GABAergic amacrine cell that is synaptically interconnected with the rod bipolar cell terminal. (1) Electron microscopy showed that the anti-GABA_A receptor antibody (62-3G1) labeled profiles that were postsynaptic to rod bipolar axons and made reciprocal synapses. (2) Indoleamine uptake (and the subsequent autofluorescence) combined with GABA_A receptor immunohistochemistry showed co-localization of the two markers in half of the receptor-positive amacrine cells. (3) Double labeling demonstrated that half of the receptor-positive somata also contained GABA. These results indicate that a GABAergic amacrine cell interconnected with the rod bipolar cell, most likely the so-called A17 amacrine cell, itself bears GABA_A receptors.     

The morphology and topographic distribution of AII amacrine cells in the cat retina

When cat retina is incubated in vitro with the fluorescent dye, 4',6-diamidino-2-phenyl-indole (DAPI), a uniform population of neurons is brightly labelled at the inner border of the inner nuclear layer. The dendritic morphology of the DAPI-labelled cells was defined by iontophoretic injection of Lucifer yellow under direct microscopic control: all the filled cells had the narrow-field bistratified morphology that is distinctive of the AII amacrine cells previously described from Golgi-stained retinae. Although the AII amacrines are principal interneurons in the rod-signal pathway, their density distribution does not follow the topography of the rod receptors, but peaks in the central area like the cone receptors and the ganglion cells. There are some 512 000 AII amacrines in the cat retina and their density ranges from 500 cells per square millimetre at the superior margin to 5300 cells per square millimetre in the centre (retinal area is 450 mm2). The isodensity contours are kite-shaped, particularly at intermediate densities, with a horizontal elongation towards nasal retina. The cell body size and the dendritic dimensions of AII amacrines increase with decreasing cell density. The lobular dendrites in sublamina a of the inner plexiform layer span a restricted field of 16-45 microns diameter, while the arboreal dendrites in sublamina b form a varicose tree of 18-95 microns diameter. The dendritic field coverage of the lobular appendages is close to 1.0 (+/- 0.2) at all eccentricities whereas the coverage of the arboreal dendrites doubles within the first 1.5 mm and then remains constant at 3.8 (+/- 0.7) throughout the periphery.     

Synaptic inputs to the ganglion cells in the tiger salamander retina

The postsynaptic potentials (PSPs) that form the ganglion cell light response were isolated by polarizing the cell membrane with extrinsic currents while stimulating at either the center or surround of the cell's receptive field. The time-course and receptive field properties of the PSPs were correlated with those of the bipolar and amacrine cells. The tiger salamander retina contains four main types of ganglion cell: "on" center, "off" center, "on-off", and a "hybrid" cell that responds transiently to center, but sustainedly, to surround illumination. The results lead to these inferences. The on-ganglion cell receives excitatory synpatic input from the on bipolars and that synapse is "silent" in the dark. The off-ganglion cell receives excitatory synaptic input from the off bipolars with this synapse tonically active in the dark. The on-off and hybrid ganglion cells receive a transient excitatory input with narrow receptive field, not simply correlated with the activity of any presynaptic cell. All cell types receive a broad field transient inhibitory input, which apparently originates in the transient amacrine cells. Thus, most, but not all, ganglion cell responses can be explained in terms of synaptic inputs from bipolar and amacrine cells, integrated at the ganglion cell membrane.     

Coerulospinal cells containing neuropeptide Y in the cat.

Spinally projecting neuropeptide Y (NPY)-immunoreactive cells were sought in the feline locus coeruleus (LC) nuclear complex after horseradish peroxidase (HRP) injection into the lumbar cord; HRP injection was followed by intracerebroventricular colchicine administration. Our results revealed that a significant number (approximately 20% of all descending cells from the LC complex) of spinally projecting NPY-immunoreactive neurons arise from the LC alpha, the subcoeruleus and the K?lliker-Fuse nuclei. Other nonspinally projecting NPY-containing cells were also evident in the laterodorsal tegmental nucleus and the LCd, in addition to those occurring in the aforementioned LC nuclear complex.     

The morphology and topographic distribution of substance-P-like immunoreactive amacrine cells in the cat retina

In cat retinal wholemounts, substance-P-like immunoreactivity (SP-IR) was localized in a distinct population of amacrines whose cell bodies were normally placed in the ganglion cell layer. Although displaced amacrines accounted for 80-95% of the SP-IR amacrines in peripheral retina, this proportion decreased considerably within the area centralis, accounting for 50-80% of the labelled cells at maximum density. The SP-IR cells in both the inner nuclear and ganglion cell layers gave rise to well-defined varicose dendrites of uniform appearance that stratified around 60% depth (S3/S4) of the inner plexiform layer. In addition, sparse fine dendrites in stratum 1 (S1) could sometimes be traced to inner nuclear cells and occasionally to displaced amacrines. The combined SP-IR cell density ranged from less than 50 cells mm-2 in the far periphery to more than 500 cells mm-2 in the area centralis; the maximum density showed little individual variation despite wide differences in the proportion of displaced cells. The 39,000 SP-IR amacrines in a mapped retina had a triangular topographic distribution, with intermediate isodensity lines extending vertically in superior retina and horizontally along both arms of the visual streak. Colocalization experiments established that all SP-IR cells in cat retina showed GABA-like immunoreactivity, and that the SP-IR amacrines were quite distinct from the cholinergic amacrines identified by choline acetyltransferase immunohistochemistry.     

Spatiotemporal frequency responses of cat retinal ganglion cells

Spatiotemporal frequency responses were measured at different levels of light adaptation for cat X and Y retinal ganglion cells. Stationary sinusoidal luminance gratings whose contrast was modulated sinusoidally in time or drifting gratings were used as stimuli. Under photopic illumination, when the spatial frequency was held constant at or above its optimum value, an X cell's responsivity was essentially constant as the temporal frequency was changed from 1.5 to 30 Hz. At lower temporal frequencies, responsivity rolled off gradually, and at higher ones it rolled off rapidly. In contrast, when the spatial frequency was held constant at a low value, an X cell's responsivity increased continuously with temporal frequency from a very low value at 0.1 Hz to substantial values at temporal frequencies higher than 30 Hz, from which responsivity rolled off again. Thus, 0 cycles X deg-1 became the optimal spatial frequency above 30 Hz. For Y cells under photopic illumination, the spatiotemporal interaction was even more complex. When the spatial frequency was held constant at or above its optimal value, the temporal frequency range over which responsivity was constant was shorter than that of X cells. At lower spatial frequencies, this range was not appreciably different. As for X cells, 0 cycles X deg-1 was the optimal spatial frequency above 30 Hz. Temporal resolution (defined as the high temporal frequency at which responsivity had fallen to 10 impulses X s-1) for a uniform field was approximately 95 Hz for X cells and approximately 120 Hz for Y cells under photopic illumination. Temporal resolution was lower at lower adaptation levels. The results were interpreted in terms of a Gaussian center-surround model. For X cells, the surround and center strengths were nearly equal at low and moderate temporal frequencies, but the surround strength exceeded the center strength above 30 Hz. Thus, the response to a spatially uniform stimulus at high temporal frequencies was dominated by the surround. In addition, at temporal frequencies above 30 Hz, the center radius increased.     

Topography of horizontal cells in the retina of the domestic cat.

Neurofibrillar methods stain a class of horizontal cells in the cat retina which are shown to be identical with the A-type horizontal cell of Golgi-staining. Thus all of the A-type cells of a single retina can be observed. On this basis the changes in density and dendritic field size of A-type horizontal cells with respect to retinal eccentricity were measured. The decrease in density from centre to periphery is balanced by a corresponding increase in size of the dendritic field. Consequently each retinal point--independent of retinal position--is covered by the dendritic fields of three of four A-type horizontal cells. The nuclei and nucleoli of B-type horizontal cells could also be recognized in neurofibrillar-stained material and thus their distribution was determined. The density ratio B-type: A-type is 2.8 +/- 0.4 and does not vary much from the centre to the periphery of the retina. Each retinal point is also covered by four B-type horizontal cells. Thus a single cone can contact a maximum of eight horizontal cells. The rate of density decrease from centre to periphery is closely similar in cones and horizontal cells but greater in ganglion cells.     

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.