Dwight A. Burkhardt

Effects of synaptic blocking agents on the depolarizing responses of turtle cones evoked by surround illumination.

The effects of synaptic blocking agents on the antagonistic surround of the receptive field of cone photoreceptors were studied by intracellular recording in the retina of the turtle (Pseudemys scripta elegans). Illumination of a cones receptive-field surround typically evoked a hybrid depolarizing response composed of two components: (1) the graded synaptic feedback depolarization and (2) the prolonged depolarization, a distinctive, intrinsic response of the cone. The locus of action of synaptic blocking agents was analyzed by comparing their effects on the light-evoked response of horizontal cells, the hybrid cone depolarization evoked by surround illumination, and the pure prolonged depolarization evoked by intracellular current injection. The excitatory amino-acid antagonists, d-O-phosphoserine (DOS) and kynurenic acid (KynA), suppressed the light responses of horizontal cells and eliminated the surround-evoked, hybrid cone depolarization without affecting the prolonged depolarization evoked by current injection. Cobalt at 5-10 mM suppressed horizontal cell responses and thereby eliminated surround-evoked cone depolarizations. Cobalt (5-10 mM) also blocked the current-evoked prolonged depolarization, suggesting that the intrinsic cone mechanisms responsible for the prolonged depolarization are likely to be calcium-dependent. Various GABA agonists and antagonists were found to have no effect on the surround-evoked depolarizations of cones. In contrast, a very low concentration of cobalt (0.5 mM) selectively suppressed the light-evoked feedback depolarization of cones without affecting horizontal cell responses or the current-evoked prolonged depolarization. Cobalt at 0.5 mM thus blocks the light-evoked action of the cone feedback synapse while sparing feedforward synaptic transmission from cones to horizontal cells. The implications of the present work for the possible neurotransmitters used at these synapses is discussed.

Synaptic feedback, depolarization, and color opponency in cone photoreceptors.

For some 20 years, synaptic feedback from horizontal cells to cones has often been invoked, more or less convincingly, in discussions of retinal action and vision. However, feedback in cones has proved to be rather complex and difficult to study experimentally. The mechanisms and consequences of feedback are therefore still only partly understood. This review attempts to assess the knowns and unknowns. The limitations of the evidence for feedback are reviewed to support the position that unequivocal evidence still largely rests on intracellular recording from cones. Of the three distinct types of depolarization observed in cones, the graded depolarization is taken as the fundamental manifestation of feedback. The evidence for the hypothesis that GABA is the neurotransmitter for feedback appears reasonably strong but several complications will have to be resolved to make the hypothesis more secure. There is evidence that feedback contributes to aspects of light adaptation and spatiotemporal processing of visual information. The contributions seem modest in magnitude. The role of feedback in shaping the color-opponent responses of retinal neurons is evaluated with particular emphasis on pharmacological studies, spatial and temporal aspects of the response of chromatic horizontal cells, and the enigmatic nature of depolarizations in blue- and green-sensitive cones. On this and other evidence, it is suggested that feedback may impress some detectable wavelength dependency in some cones but the dominant mechanisms for color opponency probably reside beyond the photoreceptors.

The goldfish electroretinogram: Relation between photopic spectral sensitivity functions and cone absorption spectra1

Abstract Spectral sensitivity of the intact goldfish eye was measured by electroretinography. Experiments with the dark-adapted eye and experiments investigating the effect of flicker rate on spectral sensitivity both suggest that a comparatively large fraction of the goldfish ERG originates from the photopic system. Flicker stimulation was used to measure photopic spectral sensitivity. These data were analysed with regard to the absorption spectra of the goldfish cones. The photopic curve was not adequately derived from a conventional additive model and it therefore is suggested that a more complex mode of interaction may be operative. A special method was used to determine the action spectrum of a red-sensitive photopic mechanism. This action spectrum seems to be highly correlated with the absorption spectrum of the red-sensitive cones.

Responses of ganglion cells to contrast steps in the light-adapted retina of the tiger salamander

The impulse discharge of single ganglion cells was recorded extracellularly in superfused eyecup preparations of the tiger salamander (Ambystoma tigrinum). Contrast flashes (500 ms) were applied at the center of the receptive field while the retina was light adapted to a background field of 20 cd/m2. The incidence of cell types in a sample of 387 cells was: ON cells (4%), OFF cells (28%), and ON/OFF cells (68%). Quantitative contrast/response measurements were obtained for 83 cells. On the basis of C50, the contrast necessary to evoke a half-maximal response, ON/OFF cells fell into 3 groups: (1) Positive Dominant (26%), (2) Balanced (23%), and (3) Negative Dominant (51%). Positive Dominant cells tended to be relatively contrast insensitive. On the other hand, many Negative Dominant cells showed remarkably low C50 values and very steep contrast/response curves. Contrast gain to negative contrast averaged 8.5 impulses/s/% contrast, some four times greater than that evoked by positive contrast. In most ON/OFF cells, the latency of the first spike evoked by a negative contrast step was much shorter (40-100 ms) than that evoked by a positive contrast step of equal contrast. OFF cells typically showed higher C50 values, larger dynamic ranges, and longer latencies than those of Negative Dominant ON/OFF cells. Thus, different pathways or mechanism apparently mediate the off responses of OFF and ON/OFF cells. In sum, the light-adapted retina of the tiger salamander is strongly biased in favor of negative contrast, as shown by the remarkably high contrast sensitivity and faster response of Negative Dominant cells, the remarkably low incidence of ON cells, and the insensitivity of Positive Dominant cells. Some possible underlying influences of bipolar and amacrine cells are discussed.

Light adaptation and excitation: Lateral spread of signals within the frog retina

Abstract The spatial spread of rapid light adaptation was quantitatively studied in the frog retina by simultaneously recording the impulse discharge of a single on-off neuron along with a local graded potential, The Proximal Negative Response (PNR). The neurons adaptive field profile (AFP) was mapped with small spots of variable position and found to be much narrower than the neurons excitatory receptive field and nearly identical to the AFP of the PNR. The adapting and excitatory effects of concentric spots of variable radius yielded similar radiussensitivity curves for PNR and neuron. Implications of these and other findings for lateral mechanisms of adaptation, amacrine-ganglion cell coupling and movement detection are discussed.

Symmetry and constancy in the perception of negative and positive luminance contrast

The perception of suprathreshold luminance contrast was investigated by forced-choice psychophysical procedures that were designed to define contrast equivalence relations. Observers compared the perceived contrast of rectangular bars that were presented for 500 msec at 3.9 deg on opposite sides of the fovea. The results show a nearly symmetrical relation between the perception of negative and positive contrast that is largely invariant over four decades of background luminance. Thus, for any fixed background luminance, equal absolute contrasts evoke approximately equal perceived contrasts. Symmetry also held with variations in the width, the eccentricity, and the focus of the bars. Symmetry was investigated further by determining equivalent contrast relations for negative contrasts as a function of background luminance and by contrast scaling. These results show evidence for nearly perfect contrast constancy for targets of low to moderate contrast and departures form constancy for high-contrast targets. These new findings on negative contrast, symmetry, and contrast constancy are discussed in relation to underlying mechanisms for contrast perception and classic experiments on brightness and lightness constancy.

Center-surround organization in bipolar cells: Symmetry for opposing contrasts

Intracellular recordings were obtained from 73 cone-driven bipolar cells in the light-adapted retina of the tiger salamander (Ambystoma tigrinum). Responses to flashes of negative and positive contrast for centered spots and concentric annuli of optimum spatial dimensions were analyzed as a function of contrast magnitude. For both depolarizing and hyperpolarizing bipolar cells, it was found that remarkably similar responses were observed for the center and surround when comparisons were made between responses of the same response polarity and thus, responses to opposite contrast polarity. Thus, spatial information and contrast polarity appear to be rather strongly confounded in many bipolar cells. As a rule, the form of the contrast/response curves for center and surround approximated mirror images of each other. Contrast gain and C50 (the contrast required for half-maximal response) were quantitatively similar for center and surround when comparisons were made for responses of the same response polarity. The average contrast gain of the bipolar cell surround was 3-5 times higher than that measured for horizontal cells. Contrast/latency measurements and interactions between flashed spots and annuli showed that the surround response is delayed by 20-80 ms with respect to that of the receptive-field center. Cones showed no evidence for center-surround antagonism while for bipolar cells, the average strength of the surround ranged from about 50% to 155% of the center, depending on the test and response polarity. The results of experiments on the effects of APB (100 microM) on depolarizing bipolar cells suggest that the relative contribution of the feedback pathway (horizontal cell to cones) and the feedforward pathway (horizontal cell to bipolar cell) to the bipolar surround varies in a distributed manner across the bipolar cell population.

Ganglion cell responses of the mudpuppy retina to flashing and moving stimuli.

Abstract The impulse discharges of over 300 ganglion cells were studied in the mudpuppy retina. By using flashing and moving stimuli, four cell types were recognized: sustained-ON, sustained-OFF. transient-ON/OFF, and directionally selective (DS). None of these characteristically exhibited spontaneous activity. Surround inhibition was demonstrable with only suprathreshold stimuli in ON-celLs. whereas it was also revealed with threshold stimuli in OFF- and ON/OFF-cells. Sensitization (the lowering of test-flash threshold as background diameter is increased) is found in OFF- and ON/OFFcells, but not in ON-cells. The directionality of DS-cells is independent of stimulus contrast and thus it constitutes the first unequivocal demonstration of directional cells in an amphibian visual system.

cellular mechanisms for color-coding in holostean retinas and the evolution of color vision

Electrophysiological recording and microspectrophotometry were used to analyze retinal function in representatives of the two surviving genera of holostean grade fish--the bowfin (Amia calva) and gars (Lepisosteus sp.). The properties of the cone photopigments, horizontal cells and ganglion cells show that these holostean retinas have cellular mechanisms for color vision which are fundamentally similar to those previously described for teleosts, turtle and mammals. These findings suggest that trichromatic receptor systems and opponent color-coding mechanisms may have evolved in primitive Neopterygii or more ancient fish, before the advent of teleosts. In conjunction with other recent data on living representatives of primitive fishes, these findings also add renewed plausibility for the view that vertebrate color vision could have taken a common origin some 400 million years ago from an ancestral aquatic jawed vertebrate.

Contrast processing by ON and OFF bipolar cells.

Much of what is currently known about the visual response of retinal bipolar cells is based on studies of rod-dominant responses to flashes in the dark in the isolated retina. This minireview summarizes quantitative findings on contrast processing in the intact light-adapted retina based on intracellular recording from more than 400 cone-driven bipolar cells in the tiger salamander: 1) In the main, the contrast responses of ON and OFF cells are surprisingly similar, suggesting a need to refine the view that ON and OFF cells provide the selective substrates for processing of positive and negative contrasts, respectively. 2) Overall, the response is quite nonlinear, showing very high gain for small contrasts, some 10-15 times greater than that of cones, but then quickly approaches saturation for higher contrasts. 3) Under optimal conditions of light adaptation, both classes of bipolar cells show evidence for efficient coding with respect to the contrasts in natural images. 4) There is a marked diversity within both the ON and OFF bipolar cell populations and an absence of discrete subtypes. The dynamic ranges bracket the range of contrasts in nature. 5) For both ON and OFF cells, the receptive field organization shows a striking symmetry between center and surround for responses of the same polarity and thus opposite contrast polarities. 6) The latency difference between ON and OFF cells is about 30 ms, which seems qualitatively consistent with a delay due to the G-protein cascade in ON bipolar cells. 7) In sum, we report quantitative evidence for at least 11 transformations in signal processing that occur between the voltage response of cones and the voltage response of bipolar cells.