Suppressive rod-cone interactions: evidence for separate retinal (temporal) and extraretinal (spatial) mechanisms in achromatic vision.

We investigated the influence of selective rod light and dark adaptation on cone-mediated sensitivity to monocular displays modulated sinusoidally in both spatial and temporal domains. Rod light adaptation (1) increased sensitivity to high spatial frequencies [> or = 8 cycles per degree (cpd)] flickered slowly (< or = 2 Hz), an effect that we refer to as grating suppressive rod-cone interaction (gSRCI); (2) increased sensitivity to low spatial frequencies (< or = 2 cpd) flickered rapidly (> or = 8 Hz), an effect that we refer to as flicker suppressive rod-cone interaction (fSRCI); and (3) had relatively little influence on intermediate temporal-spatial-frequency combinations. The magnitudes of both gSRCI and fSRCI increased as the retinal position of the test display was increasingly displaced parafoveally. In parafoveal retina, both forms of suppressive rod-cone interaction increased as the overall dimension of the test stimulus decreased. However, sensitivity to high spatial frequencies is equally well influenced by adaptation of the viewing and the contralateral eye, while the adapted state of the nonviewing eye negligibly influences sensitivity to rapid flicker. Moreover, gSRCI cannot be observed with a small (30-arcmin) grating restricted to the fovea, while fSRCI is a prominent effect with small foveal test stimuli. Collectively, these results and neurobiological evidence suggest that fSRCI reflects a mechanism restricted to distal retinal, while gSRCI involves extraretinal neural circuitry.

Functional role of GABA in cat retina: I. Effects of GABAA agonists.

Putative GABAergic mechanisms were studied in perfused cat retina by means of intracellular recording and application of GABA and the GABAA agonists delta-amino valeric acid (dAVA), muscimol, and THIP. In contrast to results reported previously for cold-blooded vertebrates, introduction of 20 mM GABA into the superfusate had no influence upon the response properties of cat retinal horizontal cells (HCs). In common with results reported in cold-blooded vertebrates, introduction of the GABAA agonists dAVA (2-12 mM) and THIP or muscimol (0.2-1 mM) had four consistent reversible influences upon the response properties of cat retinal HCs: (1) they reduced photic-response amplitude, (2) slowed response onset, (3) slowed response offset, and (4) depolarized the dark membrane potential. Both rod and cone signal components were affected. GABAA agonists had similar influences upon both the time course and amplitude of responses recorded from amacrine and ganglion cells. In all cell types examined, the influence upon response kinetics was made particularly apparent with rapidly flickering stimuli. Flicker responses were reduced in amplitude much more than sustained responses. These results suggest that, in addition to other influences, GABAergic action serves to modify the time course of photic responses in both the inner and outer plexiform layer of mammalian retina making responses slower and less phasic.

Functional role of GABA in cat retina: II. Effects of GABAA antagonists.

Putative GABAergic mechanisms were studied in the cat retina by exogenous application of the GABAA antagonists picrotoxin (PTX), native bicuculline (BCC), and bicuculline methyl bromide (BCC MeBr). When recording intracellular responses from horizontal cells (HCs) and amacrine cells as well as electroretinograms (ERGs), drugs were added to the perfusate used to maintain the isolated eyecup; when recording extracellular spikes from ganglion cells of anesthetized cats, drugs were introduced by iontophoretic injection. Both PTX and BCC MeBr had relatively little influence upon the response properties of HCs. In contrast, native BCC tended to decrease the amplitude of and to slow the photic response to light onset and both to quicken and to increase the amplitude of response to light offset; in the presence of native BCC, HC responses were dominated by a prominent spike-like "Off-overshoot." The influence of GABAA agonists upon HC responses was not blocked by GABAA antagonists. ERG b-wave amplitude was reduced both by PTX and by native BCC, but was not influenced by BCC MeBr. Latency (time to half-peak) was increased by low doses of native BCC, and to a lesser extent PTX but not BCC MeBr. Rod-amacrine On-transient responses were increased in amplitude by PTX. Extracellular recordings from On- and Off- X and Y ganglion cell types became considerably more transient with application of either PTX, native BCC, or BCC MeBr; this tendency was greater in Off-type ganglion cells. Collectively, these results strengthen conclusions from the previous paper suggesting that GABA serves to slow onset and offset kinetics of retinal neurons, making them more sustained and less phasic. They also suggest that in mammalian retina heterogeneous types of GABAA receptors exist, segregated into different zones: a distal zone, sensitive only to native BCC, a central zone sensitive to both native BCC and PTX, and a proximal zone sensitive to native BCC, BCC methyl halides (BCC MeH), and PTX. Only the proximal zone obeys conventional GABAA pharmacology.

Tonic interocular suppression, binocular summation, and the visual evoked potential.

PURPOSE: Psychophysical studies have shown that a dark-adapted eye exerts a tonic interocular suppression (TIS) upon spatial vision mediated by the contralateral eye. The present study was designed to demonstrate TIS by means of visual evoked potential (VEP) procedures. METHODS: Evoked cortical potentials were obtained in response to reversing checkerboard patterns with fundamental Fourier frequencies between 3 and 12 cycles per degree. Responses were obtained under monocular viewing conditions when the contralateral "adapting" eye was dark adapted, under monocular viewing conditions when the adapted state of the adapting eye was experimentally manipulated, or under binocular viewing conditions. Data were collected from three healthy young men, two native regarding purpose of experimentation. RESULTS: Regardless of spatial frequency, monocular responses evoked by stimulating a "test eye" were always smaller in amplitude when the contralateral adapting eye was dark adapted than when adapted to a dim, homogeneous field. The monocular evoked response obtained in the presence of an interocular adapting field was similar in amplitude to the binocular evoked response. During dark adaptation of the contralateral adapting eye, the amplitude of the monocular evoked response decreased: the time course of this decline follows that of psychophysically measured rod thresholds in the directly adapted eye. CONCLUSIONS: TIS is easily demonstrated by means of VEP as well as psychophysical procedures. The well-known increase in VEP amplitude resulting from binocular viewing may be attributable to the removal of TIS rather than to "physiologic, binocular summation."

Influence of rod adaptation upon cone responses to light offset in humans: I. Results in normal observers.

Dark-adapted rods exert a tonic suppressive influence upon cone-mediated sensitivity to rapid flicker, a phenomenon called suppressive rod-cone interaction (SRCI). However, rod dark adaptation has negligible influence upon cone-mediated thresholds measured with more usual psychophysical procedures. The present study separately examined the influences of rod light and dark adaptation upon cone-mediated sensitivity to transient increases or decreases in illumination using sawtooth flicker with rapid-on (ramp-off) or rapid-off (ramp-on) waveforms. In the parafoveal retina, cones alone were stimulated with flicker by spatially superimposing long- and short-wavelength stimuli presented in counterphase and matched in scotopic illuminance. Several different adaptation procedures were used. For higher (greater than 4 Hz) frequencies, sensitivity of cones to both waveforms is nearly identical under any condition of adaptation; sensitivity decreases as rods progressively dark adapt. A considerably different situation exists for slower frequencies (1-4 Hz). Sensitivity of cones to rapid-off flicker is appreciably greater under light-adapted conditions confirming recent observations by Bowen et al. (1989). But as rods progressively dark adapt, sensitivity of cones to rapid-off waveforms decreases considerably while sensitivity to rapid-on waveforms is much less affected; in the totally dark-adapted eye, sensitivity to both waveforms is identical. These results confirm and extend recent physiological observations in amphibian retina (Frumkes & Wu, 1990) suggesting that SRCI specifically involves responses to transient decreases in illumination.

Influence of rod adaptation upon cone responses to light offset in humans: II. Results in an observer with exaggerated suppressive rod-cone interaction.

In normal observers, sensitivity of cones to rapid sinusoidal flicker decreases by about 0.7 log units as rods progressively dark adapt. However, Arden and Hogg (1985) described a night-vision disorder characterized by normal rod sensitivity but exaggerated suppressive rod-cone interaction (SRCI). We refer to this condition as the exaggerated SRCI syndrome (ESS). The present paper examines the influence of rod-adaptation upon cone-mediated responses to light onset and offset in an observer with ESS. Under all conditions of adaptation examined, sensitivity of cones to rapid-on waveforms is indistinguishable to that of a normal observer tested under identical circumstances; rod sensitivity is also normal. However, the sensitivity of cones to transient decreases in illumination is clearly subnormal under light-adapted conditions. This deficit in cone responsiveness to light offset becomes increasingly subnormal as rods dark adapt and, when completely dark adapted, the ESS observer is nearly blind to 1 Hz rapid-off sawtooth waveforms. These results strongly bolster previous results that suggest that suppressive rod-cone interaction is restricted to the response to transient decreases in illumination.

Tonic interocular suppression and binocular summation in human vision.

1. Spatial sensitivity of human foveal vision was examined using sinusoidally modulated gratings. Our primary concern was the influence of interocular light adaptation upon monocular visibility. 2. Interocular adapting influences depend upon spatial frequency and adapting luminance. Interocular adaptation has a negligible influence upon the sensitivity to 1 cycle/deg gratings. Any visible interocular adapting field improves the sensitivity to intermediate spatial frequencies (2-5 cycles/deg). 3. Brighter interocular backgrounds (greater than 0.1 cd/m2) improve sensitivity to higher spatial frequencies (10-20 cycles/deg). 4. The interocular adapting influences summarized in (2) and (3) above cannot be duplicated by monocular or binocular adaptation. Similarly, monocular or binocular adaptation have negligible influences upon binocular visibility. 5. The interocular adapting effect summarized in (3) above can be duplicated by pressure blinding the contralateral eye. We conclude that monocular spatial sensitivity is subject to a tonic interocular suppression (TIS) from the dark-adapted eye. 6. The spatial sensitivity resulting from binocular viewing is nearly identical to that observed by combining monocular viewing with interocular light adaptation. We suggest that the improvement in sensitivity resulting from two-eyed viewing may be attributable to the removal of TIS instead of to binocular physiological summation.

Nyctalopia with normal rod function: a suppression of cones by rods.

Twenty-nine patients with exaggerated rod-cone interaction are described. All were referred because they appeared to suffer from night blindness. ERG and EOGs were performed but were normal. However, investigation with a modified dark-adaptometry technique showed that in these patients cone flicker thresholds rise considerably more during dark adaptation than is normal, and this is sufficient to explain the symptoms. In one case, the condition appears familial. Many patients report their symptoms begin in early adult life and slowly get worse, but we have no objective evidence of progression.

Independent influences of rod adaptation on cone-mediated responses to light onset and offset in distal retinal neurons.

1. The influence of rod adaptation on cone-mediated intracellular responses of distal retinal neurons was examined in the larval tiger salamander. Rods were selectively stimulated by the use of 450-520 nm adapting stimuli too dim to appreciably influence cones. Cones were primarily stimulated with the use of deep-red stimuli (maximally sensitive to wavelengths greater than 650 nm). The qualitative properties of rod-cone interaction were assessed with the use of several different photic-stimulus paradigms. 2. Confirming results of prior studies, we showed that rod adaptation changed the time course of cone-mediated responses to the onset of square-wave light flashes in horizontal cells (HCs); rod adaptation had no similar influence in other distal retinal neurons. Rod adaptation also enhanced cone-mediated responses to rapid flicker in cones, hyperpolarizing (HPBCs) and depolarizing (DPBCs) bipolar cells, as well as HCs. 3. We also examined the influence of rod-stimulating background fields on cone-mediated responses to slow (approximately 1-Hz) flicker composed of sawteeth with a rapid onset (ramp offset) or with a rapid offset (ramp onset). Such stimulation maintained a constant state of long-term adaptation while providing cones with transient-ON or transient-OFF stimulation. 4. Rod adaptation speeds up the response of HCs to rapid onset and increases response amplitude. Rod adaptation had no reliable influence on response to rapid onset in cones or bipolar cells. 5. Rod adaptation enhanced the amplitude of responses of HCs to rapid offset without altering response time course. 6. Rod adaptation greatly enhanced the amplitude of DPBC responses to rapid offset having no reliable influence on the time course of the response. 7. Rod adaptation caused responses of HPBCs to rapid offset to become much more transient. Rod backgrounds had a similar but smaller and less reliable influence on the response of cones to rapid offset. 8. The foregoing results indicate that rod adaptation exerts a minimum of two separate influences on cone-mediated responses in distal amphibian retina. Changes at light onset must reflect the operation of a mechanism that alters response kinetics of the HC membrane. Changes at light offset reflect the operation of a separate mechanism or set of mechanisms that must act in part presynaptically to the HCs.

Physiological and pharmacological analysis of suppressive rod-cone interaction in Necturus retina [corrected].

1. Intracellular recordings were obtained from retinal neurons of the mudpuppy, Necturus, while superfusing the eyecup with various pharmacologic agents. In most experiments, the retina was continuously stimulated with a small spot of red light that was centered over the recording electrode and flickering at rates too fast for amphibian rods to follow. The retina was additionally stimulated intermittently with a dim, spatially diffuse background field of 520 nm wavelength. 2. In general, the dim background greatly enhanced flicker responsiveness. We (16) previously called this effect suppressive rod-cone interaction (SRCI) and showed it reflects a tonic suppressive influence on cone pathways that is removed by selective rod-light adaptation. 3. Lead chloride has been claimed to selectively block rod-related retinal responses (13, 35). While recording from horizontal cells lead chloride decreases responses to the dim, diffuse light flashes, enhances the frequency entrained response attributable to cones, and eliminates a background influence on flicker responses. 4. O-phospho-D-serine (DOP), kynurenic acid (KyA), and piperidine dicarboxylic acid are known to act on horizontal cells as antagonists of the photoreceptor neurotransmitter (26, 32, 33). In both depolarizing and hyperpolarizing bipolar cells, these agents enhance flicker responsiveness with no background present and prevent background enhancement of flicker. 5. Mudpuppy cones were found to have a receptive-field surround, which under our stimulus conditions is attributable to rod input. KyA, which is unknown to have any direct influence on photoreceptors, totally blocks this surround mechanism. This indicates that the cone-surround mechanism is attributable to horizontal cell feedback. The influence of KyA on SRCI in cones is similar to that observed in recordings from depolarizing bipolar cells. 6. Most sustained third-order neurons demonstrate SRCI. In these cells, SRCI is blocked by DOP or KyA. Most ON-OFF neurons fail to demonstrate SRCI under control circumstances. The ON-response of these cells is blocked by 2-amino-4-phosphonobutyric acid (31) which leaves the OFF-response intact. While their ON-response is blocked, ON-OFF neurons demonstrate SRCI. 7. The foregoing results indicate that SRCI reflects a tonic, inhibitory influence of horizontal cells on cone pathways that is removed by light-adapting rods. In part, SRCI must involve horizontal cell feedback onto cones. SRCI in third-order neurons appears to largely reflect distal retinal processing.

Rod light and dark adaptation influence cone-mediated spatial acuity.

The influence of rod light and dark adaptation upon cone mediated spatial acuity was studied in the near parafoveal retina of normal human observers. The luminance just necessary to detect squarewave test gratings of variable frequency provided an index of spatial acuity. Such thresholds were determined in the presence of background fields which were varied in luminance, shape, and size, or throughout the time period of dark adaptation. Spectral controls determined the type of photoreceptors influenced by all stimuli. Cone mediated spatial acuity is improved by presenting background fields too dim to directly affect cones, and is increasingly suppressed during the rod recovery stage of dark adaptation. These effects are small with spatial frequencies less than 4 c/deg but increase with spatial frequency to greater than 1 log10 unit with the highest spatial frequency examined, 21 c/deg. These influences upon cone mediated spatial vision reflect the state of long-term adaptation of rods in a large annular area surrounding the locus to which the test grating is presented. Our results emphasize the differing influences of long-term dark adaptation and prevailing luminance level upon visual acuity. Ironically, spatial acuity is optimized under dim light conditions by selectively light adapting the receptors most sensitive to feeble stimuli, the rods.

The cellular basis for suppressive rod-cone interaction.

The response to spatially focal flicker is enhanced by dim, spatially diffuse, rod-stimulating backgrounds. This effect is called suppressive rod-cone interaction (SRCI) as it reflects a tonic, suppressive influence of dark-adapted rods upon cone pathways which is removed by selective rod-light adaptation. SRCI is observed in amphibian retina with intracellular recordings from most cone-driven cells including the cones themselves, and is most obvious using stimuli flickering at frequencies too rapid for rods to follow. SRCI is blocked by glutamate analogs which selectively block the photic response of horizontal cells (HCs). In the presence of these agents, flicker responses from bipolar cells and cones are enhanced to levels normally seen only with selective rod-light adaptation. In the HCs themselves, SRCI is similarly blocked by lead chloride which blocks rod-, but not cone-related activity. In amphibian and cat HCs and in human observers, SRCI is limited by a space constant of very similar value (between 100 and 150 microns). We suggest that SRCI in all three species is mediated by HCs: in amphibians, SRCI must at least partially reflect rod-modulation of HC feedback onto cones.

Suppressive rod-cone interaction in distal vertebrate retina: intracellular records from Xenopus and Necturus.

The influence of dim diffuse adapting fields upon the sensitivity to focal photic stimulation was studied by means of intracellular recording in retinal neurons of the south african clawed frog, Xenopus and the mudpuppy, Necturus. In cones and in most horizontal and bipolar cells lacking color opponency, dim diffuse backgrounds have little influence upon the response to diffuse flicker of low (less than 2 Hz) temporal frequencies; however, with small diameter test probes of higher temporal frequencies, presentation of dim backgrounds enhance the peak-to-peak amplitude of responses to sinusoidal flicker by as much as 800%. This background enhancement effect adheres to the spectral sensitivity of the green-absorbing rod photopigment, and appears to be largely independent of the influence of the adapting field upon cone photopigment or ambient membrane potential in the recorded neuron. This effect cannot be obtained with rod-driven flicker responses. We designate this background influence on flicker, suppressive rod-cone interaction (SRCI) and attribute it to a tonic suppressive (probably inhibitory) influence of rods upon cone pathways that is removed by rod light adaptation. SRCI is also observed in the response of most sustained ON and OFF ganglion cells. However, no corresponding effect occurs in rods, color-opponent second-order neurons, ON-OFF amacrine cells, or most ON-OFF ganglion cells. The spatial and temporal limitations of SRCI observed by means of intracellular recording in amphibians are very similar to those documented by means of psychophysical or electroretinogram (ERG) procedures in a wide variety of species including humans (2, 4, 11, 22, 23, 29). SRCI most probably reflects a process that is mediated by horizontal cells. The specifics of the underlying mechanism remain unclear.

Stimulation of rods can increase cone flicker ERGs in man.

Recent psychophysical studies in man and electrophysiological studies in lower vertebrates show that dark adapted, unstimulated rods inhibit cone mediated flicker. This investigation uses comparable psychophysical and ERG procedures in man to demonstrate rod-cone interaction of this type. With either procedure the rod cone interaction cannot be demonstrated with Ganzfeld stimulation. A single small, red, flickering test field, which is a common psychophysical stimulus for testing rod-cone interaction, elicits an immeasurably small cone ERG. But an array of many such targets, flickering synchronously, is an effective psychophysical stimulus and produces an ERG with larger cone than rod components. With such an array, it can be shown that a steady, rod-stimulating background selectively enhances cone ERG components.

The influence of cone adaptation upon rod mediated flicker.

The influence of annular fields on sensitivity to sinusoidal flicker was assessed in the dark adapted parafoveal retina. Test stimuli were 2 degrees 20' in diameter; annuli had a 2 degrees 20' inner and 7 degrees 30' outer diameter. Rod flicker was studied with a "green" stimulus too dim to influence cones. Selective cone flicker was obtained using red and green flicker in counterphase and yoked together in modulation depth and scotopic illuminance. Results showed the following. (1) Annular stimulation of rods slightly facilitated rod-mediated flicker sensitivity to frequencies less than 10 Hz. In contrast, annular stimulation of cones greatly facilitated rod-mediated sensitivity, particularly for flicker frequencies greater than 7 Hz. We designate this effect, cone-rod interaction. (2) Annular stimulation of cones has a negligible influence upon sensitivity to cone-mediated flicker frequencies less than 15 Hz. In contrast, annular stimulation of rods has a large influence upon sensitivity to cone-mediated flicker, an effect we designate rod-cone interaction. (3) Within limits, both rod-cone and cone-rod interaction increase as the annular illuminance increases and as flicker frequency increases; the limiting frequency and illuminance values, however, are different for the two forms of interaction. Results are compared with prior evidence that rod and cone signals summate to produce an absolute threshold or flicker sensation. We suggest that there are at least three mechanisms for interaction between rod- and cone-related signals.

Frequency dependence in scotopic flicker sensitivity.

Sensitivity to rod-mediated (scotopic) flicker was parametrically studied in the parafoveal retina of human observers. Confirming prior studies, the present results show that sensitivity to scotopic flicker has many similarities to that at photopic levels. Specifically, our results show that the frequency response function for scotopic flicker is characterized by both low- and high-frequency cutoffs and that sensitivity to low frequencies is described by Weber's law. Overall, however, scotopic flicker sensitivity is characterized by higher increment thresholds and lower frequency tuning than photopic flicker. The influences of spatial factors and the prevailing level of illuminance on sensitivity is sufficiently different for relatively low (less than 3 Hz) and relatively high (greater than 5 Hz) temporal frequencies to suggest that they may be mediated by different channels. This possibility is also suggested by selective adaptation experiments. These show that adaptation to flicker frequencies of 3, 5, and 7 Hz have a similar influence on sensitivity to subsequent flicker which is different from the influence on 1 Hz flicker adaptation. Results are compared with prior evidence for channeling within both the scotopic and photopic visual systems.

Inhibitory influence of unstimulated rods in the human retina: evidence provided by examining cone flicker.

In the parafoveal retina of human observers, cone-mediated sensitivity to flicker decreases as rods become progressively more dark-adapted. This effect is greatest when a rod response to flicker is precluded. These results indicate that rods tonically inhibit cone pathways in the dark.

The signal-to-noise characteristics of rod-cone interaction.

1. The influence of rods on cone-mediated vision was assessed in eight human observers. To this end, increment threshold functions were obtained by determining thresholds of a cone-detected test flash (25 ms duration, 655 nm wave-length, 13' diameter) as a function of the illuminance of larger, 500 ms duration, rod-detected masking flashes. The type of photoreceptor influenced by each stimulus was carefully checked by means of a series of control procedures involving action spectra and selective rod adaptation.2. When the rod mask was 512 nm in wave-length, 40' in diameter, and less than one scotopic td in illuminance, increment threshold functions show that [Formula: see text], where I(Cth) is cone test threshold, I(R) is rod mask illuminance, and D is a dark noise term similar to that used by Barlow (1956). Further increases in I(R) have no additional influences on cone test threshold until threshold is influenced by the combined action of the mask on both rods and cones. If I(R) is expressed in terms of scotopic flux rather than illuminance, the functional relationship obtained with all rod masks 2 degrees have negligible influence on cone test threshold. We propose that I (inhibitory spatial summator), a neural locus which responds to scotopic flux provided over a very large area, attenuates the activity of E. The combined action of E and I is designated a rod channel. The response of cones and the rod channel summate at a detector. Within the detector, cone signals are distinguished from rod-related activity and intrinsic dark noise on the basis of signal-to-noise discriminations.5. The neural substrate for this rod channel most probably involves the combined action of several neurones which synapse within the inner plexiform layer of the retina. The relationship of this rod channel to other perceptual phenomena is discussed.

The influence of rod light and dark adaptation upon rod-cone interaction.

The influence of a rod-detected mask of illuminance IR on the threshold illuminance of a cone-detected test flash (ICth) was assessed while rods were recovering from the effects of a bleach, and when rods were selectively light adapted. Providing that IR was restricted to within 2 log10 units of rod mask threshold (IRth), results show that ICth/IC0 = K (square root (IR/IRth) + D), where IC0 is cone absolute threshold, D is a dark noise term and K is a proportionality constant. These data were used to obtain 'equivalent background functions' or 'Crawford (1947) transforms' (illuminance of a background field plotted against time in the dark). The same Crawford transform was obtained when either IRth or ICth (in the presence of a fixed illuminance IR) were used as equating variables. All of the foregoing results could be predicted by considering both the influence of light adaptation on rods (see Fain, 1976) and the model developed by Bauer, Frumkes & Nygaard (1982). Under dark-adapted conditions, 40' and 60' diameter rod masks of equal illuminance have very similar influences on ICth. When rods are selectively light adapted 60' masks have smaller influences on ICth. The foregoing results were used to extend the model developed in the previous paper. We suggest that rod adaptation has a distinct influence on neural loci designated E (the excitatory spatial summator) and I (the inhibitory spatial summator), and that E represents a site for both adaptation and spatial summation.