Receptive fields (RFs) of most retinal ganglion cells (RGCs) consist of an excitatory center and suppressive surround. The RF center arises from the summation of excitatory bipolar cell glutamatergic inputs, whereas the surround arises from lateral inhibitory inputs. In the retina, both gamma amino butyric acid (GABA) and glycine are inhibitory neurotransmitters. A clear role for GABAergic inhibition modulating the RGC RF surround has been demonstrated across species. Glycinergic inhibition is more commonly associated with RF center modulation, although there is some evidence that it may contribute to the RF surround. The synaptic glycinergic chloride channels are formed by three homomeric β and two homomeric α subunits that can be glycine receptor (GlyR) α1, α2, α3, or α4. GlyRα composition is responsible for currents with distinct decay kinetics. Their expression within the inner plexiform laminae and neuronal subtypes also differ. We studied the role of GlyR subunit selective modulation of RGC RF surrounds, using mice lacking GlyRα2 (Glra2−/−), GlyRα3 (Glra3−/−), or both (Glra2/3−/−). We chose this molecular genetic approach instead of pharmacological manipulation because there are no subunit selective antagonists and strychnine blocks all GlyRs. Comparisons of annulus-evoked responses among wild type (WT) and GlyRα knockouts (Glra2−/−, Glra3−/− and Glra2/3−/−) show that GlyRα2 inhibition enhances RF surround suppression and post-stimulus excitation in only WT OFF RGCs. Similarities in the responses in Glra2−/− and Glra2/3−/− RGCs verify these conclusions. Based on previous and current data, we propose that GlyRα2-mediated input uses a crossover inhibitory circuit. Further, we suggest that GlyRα2 modulates the OFF RGC RF center and surround independently. In summary, our results define a selective GlyR subunit-specific control of RF surround suppression in OFF RGCs.

A theory is presented of how global visual interactions between depth, length, lightness, and form percepts can occur. The theory suggests how quantized activity patterns which reflect these visual properties can coherently fill-in, or complete, visually ambiguous regions starting with visually informative data features. Phenomena such as the Cornsweet and Craik–O'Brien effects, phantoms and subjective contours, binocular brightness summation, the equidistance tendency, Emmert's law, allelotropia, multiple spatial frequency scaling and edge detection, figure-ground completion, coexistence of depth and binocular rivalry, reflectance rivalry, Fechner's paradox, decrease of threshold contrast with increased number of cycles in a grating pattern, hysteresis, adaptation level tuning, Weber law modulation, shift of sensitivity with background luminance, and the finite capacity of visual short term memory are discussed in terms of a small set of concepts and mechanisms. Limitations of alternative visual theories which depend upon Fourier analysis, Laplacians, zero-crossings, and cooperative depth planes are described. Relationships between monocular and binocular processing of the same visual patterns are noted, and a shift in emphasis from edge and disparity computations toward the characterization of resonant activity-scaling correlations across multiple spatial scales is recommended. This recommendation follows from the theory's distinction between the concept of a structural spatial scale, which is determined by local receptive field properties, and a functional spatial scale, which is defined by the interaction between global properties of a visual scene and the network as a whole. Functional spatial scales, but not structural spatial scales, embody the quantization of network activity that reflects a scene's global visual representation. A functional scale is generated by a filling-in resonant exchange, or FIRE, which can be ignited by an exchange of feedback signals among the binocular cells where monocular patterns are binocularly matched.

The responses of simple cells (recorded from within the striate visual cortex) were measured as a function of the contrast and the frequency of sine-wave grating patterns in order to explore the effect of contrast on the spatial and temporal phase transfer functions and on the spatiotemporal receptive field. In general, as the contrast increased, the phase of the response advanced by approximately 45 ms (approximately one-quarter of a cycle for frequencies near 5 Hz), although the exact value varied from cell to cell. The dynamics of this phase-advance were similar to the dynamics of the amplitude: the amplitude and the phase increased in an accelerating fashion at lower contrasts and then saturated at higher contrasts. Further, the gain for both the amplitude and the phase appeared to be governed by the magnitude of the contrast rather than the magnitude of the response. For the spatial phase transfer function, variations in contrast had little or no systematic effect; all of the phase responses clustered around a single straight line, with a common slope and intercept. This implies that the phase-advance was not due to a change in the spatial properties of the neuron; it also implies that the phase-advance was not systematically related to the magnitude of the response amplitude. On the other hand, for the temporal phase transfer function, the phase responses fell on five straight lines, related to the five steps in contrast. As the contrast increased, the phase responses advanced such that both the slope and the intercept were affected. This implies that the phase-advance was a result of contrast-induced changes in both the response latency and the shape/symmetry of the temporal receptive field.

We have used frequency-domain methods to characterize the spatial receptive-field structure of cat retinal W cells. For most ON- and OFF-center tonic and phasic W cells, measurements of responsivity to drifting gratings at various spatial frequencies could be adequately described by a difference-of-Gaussians (DOG) function, consistent with the presence of center and surround mechanisms that are approximately Gaussian in shape and whose signals are combined additively. Estimates of the responsivity of the center mechanisms of tonic and phasic W cells were similar, but both were significantly lower than the corresponding values for X or Y cells. The width of the center mechanisms of tonic W cells, phasic W cells, and Y cells did not differ significantly from each other, but all were significantly larger than the width of X-cell centers. Surround parameters did not vary significantly among the four groups of ganglion cells. Measurements of contrast gain in both tonic and phasic W cells gave values that were significantly lower than in X or Y cells.

Virtually all of the phasic W cells in our sample displayed evidence of spatial non-linearities in their receptive fields, in the form of either d.c. responses to drifting sine-wave gratings or second harmonic responses to counterphased gratings. The spatial resolution of the mechanism underlying these nonlinearities was typically higher than that of the center mechanism of these cells. Most tonic W cells exhibited linear spatial summation, although a subset gave strong second harmonic responses to counterphased gratings.

Spatial-responsivity measurements for most ON-OFF and directionally selective W cells were not adequately described by DOG functions. These cells did, however, show evidence of spatial nonlinearities similar to those seen in phasic W cells. Suppressed-by-contrast cells gave both modulated and unmodulated responses to drifting gratings which both appeared to involved rectification, but which differed from each other in both spatial resolution and contrast gain.

These data confirm earlier reports that the receptive fields of tonic and most ON- or OFF-center phasic W cells appear to include classical center and surround mechanisms. However, the receptive fields of some phasic cells, as well as ON-OFF and directionally selective W cells may have quite different structures. Our results also suggest that phasic, ON-OFF, directionally selective, suppressed-by-contrast, and a subset of tonic W cells may all receive nonlinear inputs with characteristics similar to those described in the receptive fields of retinal Y cells. If so, this has important implications for identifying and understanding the presynaptic circuitry of W cells, as well as the nature of their output to both telencephalic and midbrain visual targets.

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 μM 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 primary goal of this study was to expand the description of the filtering properties of the Y-cell receptive field, byquantitatively characterizing the spatial filtering properties of the receptive field’s center-and-surround components as a function of adapting light level. A range of more than five orders of magnitude in retinal illuminance were covered, including the vast majority of the cat’s functional range of vision.

Recordings were taken from optic tract fibers of Y cells in cats under general anesthesia. Sinusoidal gratings and a stimulus designed to selectively probe the properties of the surround mechanism were used. The cells’ responses to these stimuli were fit to a Gaussian center-surround receptive-field model, in which six parameters define the properties of the center and surround. Fits were made independently to data collected at each light level and changes in the values of the model’s parameters with illuminance are reported. A set of equations that summarize the changes in parameter values is given. From these summary equations, reasonable estimates of the parameters’ values can be determined across a wide range of illuminances. Hence, a quantitative model of the spatial properties of the center and surround of the Y-cell receptive field can now be derived from these equations for most of the levels of retinal illuminance experienced by a Y cell. The consistency between the description provided by our equations and results from earlier work is considered.

Extracellular recordings were made from the isolated goldfish retina during superfusion with various serotonergic agonists and antagonists to determine the effects of these drugs on the maintained activity and response properties of the ganglion cells. Superfusion of the retina with serotonin (25–500 μM) increased the maintained activity of OFF-center ganglion cells and decreased the maintained activity of ON-center ganglion cells. In addition, serotonin also attenuated the excitatory responses to annular stimuli, suggesting a decrease in the strength of surround input to the ganglion cells. The effects of serotonin on OFF-center ganglion cells were mimicked by the nonselective 5-HT1, agonist 5-MeOT and the 5-HT1 receptor agonist 8-OH-DPAT, while only 5-MeOT mimicked the action of serotonin on ON-center ganglion cells. The effects of exogenously applied serotonin on the ganglion cells could be blocked by the mixed 5-HT1/5-HT2 receptor antagonist methysergide but not by the 5-HT2 receptor antagonist mianserin or the dopamine receptor antagonist haloperidol.

These results support previous anatomical and biochemical evidence that serotonin functions in a neurotransmitter or neuromodulatory role in the teleost retina and suggest that serotonin may be involved in modulating the maintained activity and surround input to the ganglion cells. The results also indicate that two different types of receptors may mediate the actions of serotonin in the ON and OFF pathways, respectively.

The relation between the amplitude of visual responses to a checkerboard stimulus and the degree of lateral displacement of the checks was examined across different check sizes with simultaneously recorded electroretinograms (ERGs) and visual-evoked potentials (VEPs). The amplitudes of both the b–wave and the after-potential of the ERG increase linearly with pattern displacement. However, the major components of the VEP (N70 and P100) were smaller than expected from linearity for both small checks with small displacements (thresholding) and for large checks with large displacements (saturation). These results suggest that the ERG is proportional to the number of receptors stimulated, but the VEP reflects neural processes influenced by the spatial structure of the stimulus.

The outer plexiform layer of the retina contains a neural circuit in which cone synaptic terminals are electrically coupled and release glutamate onto wide-field and narrow-field horizontal cells. These are also electrically coupled and feed back through a GABAergic synapse to cones. In cat this circuit's structure is known in some detail, and much of the chemical architecture and neural responses are also known, yet there has been no attempt to synthesize this knowledge. We constructed a large-scale compartmental model (up to 50,000 compartments) to incorporate the known anatomical and biophysical facts. The goal was to discover how the various circuit components interact to form the cone receptive field, and thereby what possible function is implied. The simulation reproduced many features known from intracellular recordings: (1) linear response of cone and horizontal cell to intensity, (2) some aspects of temporal responses of cone and horizontal cell, (3) broad receptive field of the wide-field horizontal cell, and (4) center-surround cone receptive field (derived from a “deconvolution model"). With the network calibrated in this manner, we determined which of its features are necessary to give the cone receptive field a Gaussian center-surround shape. A Gaussian-like center that matches the center derived from the ganglion cell requires both optical blur and cone coupling: blur alone is too narrow, coupling alone gives an exponential shape without a central dome-shaped peak. A Gaussian-like surround requires both types of horizontal cell: the narrow-field type for the deep, proximal region and the wide-field type for the shallow, distal region. These results suggest that the function of the cone-horizontal cell circuit is to reduce the influence of noise by spatio-temporally filtering the cone signal before it passes through the first chemical synapse on the pathway to the brain.

The receptive-field properties of retinal ganglion cells (RGCs) provide information about early visual processing. In the primate retina, P cells form the largest class of RGCs (Rodieck, 1988). A detailed exploration of the dynamics of the two subdivisions of the P-cell receptive field—the center and the surround—was undertaken. In the preceding paper (Benardete & Kaplan, 1996), the first-order responses of the center and the surround of P cells were described, which were obtained with a new technique, the multiple m-sequence stimulus (Benardete & Victor, 1994). In this paper, the investigation of P-cell responses measured as S-potentials in the lateral geniculate nucleus (LGN) is continued, and significant nonlinear, second-order responses from the center and the surround are described. These responses are quantified by fitting a mathematical model, the linear-nonlinear-linear (LNL) model (Korenberg, 1973; Korenberg & Hunter, 1986; Victor, 1988) to the data. In a second series of experiments, demonstration that steady illumination of the surround modifies the gain of the center to contrast signals (see also Kaplan & Shapley, 1989) is made. In P ON cells, increasing the steady illumination of the surround decreases the gain and speeds up the center's first-order response. In P OFF cells, increasing the steady illumination of the surround increases the gain of the center while speeding up the response. The results of both sets of experiments are related to the known anatomy and physiology of the P cell.

We have studied the organization of receptive fields of ganglion cells in the isolated mouse retina and have shown that the organization is similar to that of the cat. Based upon responses to circular and annular stimuli, most ganglion cells (90%; N = 83) had receptive fields with concentric center-surround organization, either ON or OFF center. The plot of response amplitude vs. stimulus area for these cells increased to a maximum (corresponding to a diameter of 10.0 ± 2.8 deg S.E.M.; N = 13) and then decreased for larger stimuli, demonstrating the presence of an antagonistic surround. The dark-adapted sensitivity (205 ± 43.8 impulses quantum−1 rod−1; mean ± S.E.M.) did not differ from that measured for the intact preparation. We found a subset of OFF-center cells for which the dark discharge was very regular (mean coefficient of variation = 0.30). Using sinusoidal grating stimuli, we classified ganglion cells as X-like (87%) and Y-like (13%) based on spatial summation properties and the presence of subunit activity in the receptive-field center. We found no difference in the spatial-frequency preference between X-like and Y-like cells in the central retina (high cutoff frequency, 0.20 ± 0.014 cycle/deg, mean ± S.E.M.), in contrast to the marked difference between X cells and Y cells in the cat. Thus, ganglion cell receptive fields in the mouse retina resemble those of the cat, although the spatial characteristics of the receptive fields in the central retina are more homogeneous. This homogeneity would simplify the comparison of retinas from normal and mutant strains of the mouse.

The specific role of ON and OFF retinal information channels in the generation of the horizontal optokinetic nystagmus (OKN) of the frog was studied. Coil recordings of monocular eye and head OKN were obtained before and after intravitreal injection of two drugs that block either ON or OFF channels. The intravitreal injection of 2-amino-4-phosphonobutyrate (APB), a glutamate analog that selectively blocks the ON retinal channel, strongly reduced or even cancelled the monocular OKN of the head and of the eye. The intravitreal injection of another glutamate analog, the cis-2, 3-piperidine dicarboxylic acid (PDA) that especially blocks the OFF retinal channel, did not affect the gain velocity of the slow phase of both the horizontal monocular head and eye OKN, for low stimulus velocities. Our results suggest that the retinal ON information channel, but not the OFF channel, is involved in the generation of the slow phase of the OKN of the frog, at least at low drum velocities.

The receptive-field profile of the cone in cat retina was computed. The computation was based on (1) the known anatomical circuit connecting cones via narrow-field bipolar cells to the on-beta ganglion cell; (2) the known physiological receptive-field profile of the on-beta (X) cell at the corresponding eccentricity; and (3) a model in which the beta receptive field arises by linear superposition of cone receptive fields. The computed cone receptive field has a center/surround organization with a center almost as broad as that of the beta cell center. The cone surround is comparably broad to that of the beta cell but somewhat lower in peak amplitude. The problems to which the center/surround receptive field are the solution, namely, signal compression and noise reduction, apparently must be solved before the first synapse of the visual pathway.

The ganglion cells of the primate retina include two major anatomical and functional classes: P cells which project to the four parvocellular layers of the lateral geniculate nucleus (LGN), and M cells which project to the two magnocellular layers. The characteristics of the P-cell receptive field are central to understanding early form and color vision processing (Kaplan et al., 1990; Schiller & Logothetis, 1990). In this and in the following paper, P-cell dynamics are systematically analyzed in terms of linear and nonlinear response properties. Stimuli that favor either the center or the surround of the receptive field were produced on a CRT and modulated with a broadband signal composed of multiple m-sequences (Benardete et al., 1992b; Benardete & Victor, 1994). The first-order responses were calculated and analyzed in this paper (part I). The findings are: (1) The first-order responses of the center and surround depend linearly on contrast. (2) The dynamics of the center and surround are well described by a bandpass filter model. The most significant difference between center and surround dynamics is a delay of approximately 8 ms in the surround response. (3) In the LGN, these responses are attenuated and delayed by an additional 1–5 ms. (4) The spatial transfer function of the P cell in response to drifting sine gratings at three temporal frequencies was measured. This independent method confirmed the delay between the (first-order) responses of the center and surround. This delay accounts for the dependence of the spatial transfer function on the frequency of stimulation.

We studied the morphology and physiology of a unique wide-field amacrine cell in the rabbit retina. These cells displayed a stereotypic dendritic morphology consisting of a large, circular and monostratified arbor that often extended over 2 mm. Their responses contained both somatic and dendritic sodium spikes suggesting active propagation of synaptic signals within the dendritic arbor. This idea is supported by the enormous size of their ON-OFF receptive fields. Interestingly, these cells exhibited separate ON and OFF receptive fields that, while concentric, were vastly different in size. Whereas the ON receptive field of these cells extended nearly 2 mm, the OFF receptive field was typically 75% smaller. Blockade of voltage-gated sodium channels with QX-314 dramatically reduced the large ON receptive field, but had little effect on the smaller OFF receptive field. These results indicate a spatial disparity in the location of on- and off-center bipolar cell inputs to the dendritic arbor of wide-field amacrine cells. In addition, the active propagation of signals suggests that synaptic inputs are integrated both locally and globally within the dendritic arbor.

The A1 cell is an axon-bearing amacrine cell of the primate retina with a diffusely stratified, moderately branched dendritic tree (∼400 μm diameter). Axons arise from proximal dendrites forming a second concentric, larger arborization (>4 mm diameter) of thin processes with bouton-like swellings along their length. A1 cells are ON-OFF transient cells that fire a brief high frequency burst of action potentials in response to light (Stafford & Dacey, 1997). It has been hypothesized that A1 cells receive local input to their dendrites, with action potentials propagating output via the axons across the retina, serving a global inhibitory function. To explore this hypothesis we recorded intracellularly from A1 cells in an in vitro macaque monkey retina preparation. A1 cells have an antagonistic center-surround receptive field structure for the ON and OFF components of the light response. Blocking the ON pathway with L-AP4 eliminated ON center responses but not OFF center responses or ON or OFF surround responses. Blocking GABAergic inhibition with picrotoxin increased response amplitudes without affecting receptive field structure. TTX abolished action potentials, with little effect on the sub-threshold light response or basic receptive field structure. We also used multi-photon laser scanning microscopy to record light-induced calcium transients in morphologically identified dendrites and axons of A1 cells. TTX completely abolished such calcium transients in the axons but not in the dendrites. Together these results support the current model of A1 function, whereby the dendritic tree receives synaptic input that determines the center-surround receptive field; and action potentials arise in the axons, which propagate away from the dendritic field across the retina.

We recently developed a new technique to measure cone inputs to visual neurons and used this technique to seek short-wavelength-sensitive (S) cone inputs to parasol, magnocellular (MC) and midget, parvocellular (PC) ganglion cells. Here, we compare our physiological measurements of S-cone weights to those predicted by a random wiring model that assumes cells' receptive fields receive input from mixed cone types. The random wiring model predicts the average weights of S-cone input to be similar to the total percentage of S-cones but with considerable scatter, and the S-cone input polarity to be consistent with that of PC cells' surround and of MC cells' center. This is not consistent with our physiological measurements. We suggest that the ganglion cells' receptive fields may have a mechanism to avoid S-cone inputs, as is the case in the H1 horizontal cells. Previous reports of S-cone inputs, in particular substantial input to MC cells, are likely to reflect variation in prereceptoral filtering and/or the failure to correct for variation in macular pigment.

The discontinuities of phase-shifted abutting line gratings give rise to perception of an “illusory contour” (IC) along the line terminations. Neuronal responses to such ICs have been interpreted as evidence for a specialized visual mechanism, since such responses cannot be predicted from conventional linear receptive fields. However, when the spatial scale of the component gratings (carriers) is large compared to the neuron's luminance passband, these IC responses might be evoked simply by the luminance edges at the line terminations. Thus by presenting abutting gratings at a series of carrier spatial scales to cat A18 neurons, we were able to distinguish genuine nonlinear responses from those due to luminance edges. Around half of the neurons (both simple and complex types) showed a bimodal response pattern to abutting gratings: one peak at a low carrier spatial frequency range that overlapped with the luminance passband, and a second distinct peak at much higher frequencies beyond the neuron's grating resolution. For those bimodally responding neurons, the low-frequency responses were sensitive to carrier phase, but the high-frequency responses were phase-invariant. Thus the responses at low carrier spatial frequencies could be understood via a linear model, while the higher frequency responses represented genuine nonlinear IC processing. IC responsive neurons also demonstrated somewhat lower spatial preference to the periodic contours (envelopes) compared to gratings, but the optimal orientation and motion direction for both were quite similar. The nonlinear responses to ICs could be explained by the same energy mechanism underlying responses to second-order stimuli such as contrast-modulated gratings. Similar neuronal preferences for ICs and for gratings may contribute to the form-cue invariant perception of moving contours.