Weber and noise adaptation in the retina of the toad Bufo marinus

Responses to flashes and steps of light were recorded intracellularly from rods and horizontal cells, and extracellularly from ganglion cells, in toad eyecups which were either dark adapted or exposed to various levels of background light. The average background intensities needed to depress the dark-adapted flash sensitivity by half in the three cell types, determined under identical conditions, were 0.9 Rh*s-1 (rods), 0.8 Rh*s-1 (horizontal cells), and 0.17 Rh*s-1 (ganglion cells), where Rh* denotes one isomerization per rod. Thus, there is a range (approximately 0.7 log units) of weak backgrounds where the sensitivity (response amplitude/Rh*) of rods is not significantly affected, but where that of ganglion cells (1/threshold) is substantially reduced, which implies that the gain of the transmission from rods to the ganglion cell output is decreased. In this range, the ganglion cell threshold rises approximately as the square root of background intensity (i.e. in proportion to the quantal noise from the background), while the maintained rate of discharge stays constant. The threshold response of the cell will then signal light deviations (from a mean level) of constant statistical significance. We propose that this type of ganglion cell desensitization under dim backgrounds is due to a post-receptoral gain control driven by quantal fluctuations, and term it noise adaptation in contrast to the Weber adaptation (desensitization proportional to the mean background intensity) of rods, horizontal cells, and ganglion cells at higher background intensities.     

The role of steady phosphodiesterase activity in the kinetics and sensitivity of the light-adapted salamander rod photoresponse

We investigated the kinetics and sensitivity of photocurrent responses of salamander rods, both in darkness and during adaptation to steady backgrounds producing 20-3,000 photoisomerizations per second, using suction pipet recordings. The most intense backgrounds suppressed 80% of the circulating dark current and decreased the flash sensitivity approximately 30-fold. To investigate the underlying transduction mechanism, we expressed the responses as a fraction of the steady level of cGMP-activated current recorded in the background. The fractional responses to flashes of any fixed intensity began rising along a common trajectory, regardless of background intensity. We interpret these invariant initial trajectories to indicate that, at these background intensities, light adaptation does not alter the gain of any of the amplifying steps of phototransduction. For subsaturating flashes of fixed intensity, the fractional responses obtained on backgrounds of different intensity were found to "peel off" from their common initial trajectory in a background-dependent manner: the more intense the background, the earlier the time of peeling off. This behavior is consistent with a background-induced reduction in the effective lifetime of at least one of the three major integrating steps in phototransduction; i.e., an acceleration of one or more of the following: (1) the inactivation of activated rhodopsin (R*); (2) the inactivation of activated phosphodiesterase (E*, representing the complex G(alpha)-PDE of phosphodiesterase with the transducin alpha-subunit); or (3) the hydrolysis of cGMP, with rate constant beta. Our measurements show that, over the range of background intensities we used, beta increased on average to approximately 20 times its dark-adapted value; and our theoretical analysis indicates that this increase in beta is the primary mechanism underlying the measured shortening of time-to-peak of the dim-flash response and the decrease in sensitivity of the fractional response.     

Action Spectra and Adaptation Properties of Carp Photoreceptors

The mass photoreceptor response of the isolated carp retina was studied after immersing the tissue in aspartate-Ringer solution. Two electro-retinogram components were isolated by differential depth recording: a fast cornea-negative wave, arising in the receptor layer, and a slow, cornea-negative wave arising at some level proximal to the photoreceptors. Only the fast component was investigated further. In complete dark adaptation, its action spectrum peaked near 540 nm and indicated input from both porphyropsin-containing rods (λ_max ≈ 525 nm) and cones with longer wavelength sensitivity. Under photopic conditions a broad action spectrum, λ_max ≈ 580 nm was seen. In the presence of chromatic backgrounds, the photopic curve could be fractionated into three components whose action spectra agreed reasonably well with the spectral characteristics of blue, green, and red cone pigments of the goldfish. In parallel studies, the carp rod pigment was studied in situ by transmission densitometry. The reduction in optical density after a full bleach averaged 0.28 at its λ_max 525 nm. In the isolated retina no regeneration of rod pigment occurred within 2 h after bleaching. The bleaching power of background fields used in adaptation experiments was determined directly. Both rods and cones generated increment threshold functions with slopes of +1 on log-log coordinates over a 3–4 log range of background intensities. Background fields which bleached less than 0.5% rod pigment nevertheless diminished photoreceptor sensitivity. The degree and rate of recovery of receptor sensitivity after exposure to a background field was a function of the total flux (I x t) of the field. Rod saturation, i.e. the abolition of rod voltages, occurred after ≈12% of rod pigment was bleached. In light-adapted retinas bathed in normal Ringer solution, a small test flash elicited a larger response in the presence of an annular background field than when it fell upon a dark retina. The enhancement was not observed in aspartate-treated retinas.     

Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells

A rare type of mammalian retinal ganglion cell (RGC) expresses the photopigment melanopsin and is a photoreceptor. These intrinsically photosensitive RGCs (ipRGCs) drive circadian-clock resetting, pupillary constriction, and other non-image-forming photic responses. Both the light responses of ipRGCs and the behaviors they drive are remarkably sustained, raising the possibility that, unlike rods and cones, ipRGCs do not adjust their sensitivity according to lighting conditions ("adaptation"). We found, to the contrary, that ipRGC sensitivity is plastic, strongly influenced by lighting history. When exposed to a constant, bright background, the background-evoked response decayed, and responses to superimposed flashes grew in amplitude, indicating light adaptation. After extinction of a light-adapting background, sensitivity recovered progressively in darkness, indicating dark adaptation. Because these adjustments in sensitivity persisted when synapses were blocked, they constitute "photoreceptor adaptation" rather than "network adaptation." Implications for the mechanisms generating various non-image-forming visual responses are discussed.     

Control of Retinal Sensitivity : II. Lateral Interactions at the Outer Plexiform Layer

Test stimuli, presented at the center of the bipolar cell receptive field, spanning less than 2 log units of intensity, elicit the full range of graded response. The intensity range of test stimuli that elicits the graded response depends upon the background conditions. A higher range of log test intensities is required to elicit the graded bipolar response in the presence of surround backgrounds. But surround backgrounds can also serve to unsaturate the bipolar response and thereby increase sensitivity under certain conditions. The results suggest that a second stage of sensitivity-control is mediated by the horizontal cell system at the outer plexiform layer, concatenated with the effects of adaptation in the photoreceptors.     

The Duplex Nature of the Retina of the Nocturnal Gecko as Reflected in the Electroretinogram

The effect of light and dark adaptation on the electrical activity in two species of nocturnal gecko, Hemidactylus turcicus and Tarentola mauritanica was studied. The electroretinogram of both species changes from the scotopic type in the dark-adapted state to the photopic type after strong light adaptation. For the scotopic response fusion frequencies up to 18 flashes per sec. are obtained in both species. For the photopic response fusion frequencies up to 50 flashes per sec. are seen in Tarentola, and up to 25 flashes per sec. in Hemidactylus. Proceeding from dark to light adaptation the increment threshold (dI) is measured at different levels of adaptive illumination (I). At low levels of illumination the dI/I ratio is found to be small and at high levels of illumination to be large. No difference in the dI/I ratio is obtained for test lights of 462 and 605 mµ. During dark adaptation the change of threshold after exposure to moderate and weak lights (up to 10³ times dark threshold) is rather fast. After light adaptation to strong light (10⁶ times dark threshold) duplex dark adaptation curves are seen with a break separating a fast and a slow phase of dark adaptation. The significance of these results from a retina which possesses sense cells of only one type is discussed.     

Dynamics of skate horizontal cells

The all-rod retina of the skate (Raja erinacea or R. oscellata) is known to have the remarkable capability of responding to incremental flashes superimposed on background intensities that initially block all light-evoked responses and are well above the level at which rods saturate in mixed rod/cone retinas. To examine further the unusual properties of the skate visual system, we have analyzed responses of their horizontal cells to intensity-modulated step, sinusoidal, and white-noise stimuli. We found that during exposures to mean intensities bright enough to block responses to incremental stimuli, decremental stimuli were also initially blocked. Thereafter, the horizontal cells underwent a slow recovery phase during which there was marked nonlinearity in their response properties. The cell first (within 2-3 min) responded to decrements in intensity and later (after greater than 10 min) became responsive to incremental stimuli. After adaptation to a steady state, however, the responses to intensity modulation were nearly linear over a broad range of modulation depths even at the brightest mean levels of illumination. Indeed, examination of the steady-state responses over a 5-log-unit range of mean intensities revealed that the amplitude of the white noise-evoked responses depended solely on contrast, and was independent of the retinal irradiance as the latter was increased from 0.02 to 20 muW/cm2; i.e., contrast sensitivity remained unchanged over this 1,000-fold increase in mean irradiance. A decrement from the mean as brief as 2 s, however, disturbed the steady state. Another unexpected finding in this all-rod retina concerns surround-enhancement, a phenomenon observed previously for cone-mediated responses of horizontal cells in the retinas of turtle and catfish. While exposure to annular illumination induced response compression and a pronounced sensitivity loss in response to incremental light flashes delivered to the dark central region, the cell's sensitivity showed a significant increase when tested with a white noise or sinusoidally modulated central spot. Unlike horizontal cells in other retinas studied thus far, however, response dynamics remained unchanged. Responses evoked either by a small spot (0.25-mm diam) or by a large field light covering the entire retina were almost identical in time course. This is in contrast with past findings from cone-driven horizontal cells whose response waveform (dynamics) was dependent upon the size of the retinal area stimulated.     

INTERMITTENT STIMULATION BY LIGHT : III. THE RELATION BETWEEN INTENSITY AND CRITICAL FUSION FREQUENCY FOR DIFFERENT RETINAL LOCATIONS

When measurements of the critical fusion frequency for white light over a large range of intensities are made with the rod-free area of the fovea, the relation between critical frequency and log I is given by a single sigmoid curve, the middle portion of which approximates a straight line whose slope is 11.0. This single relation must be a function of the foveal cones. When the measurements are made with a retinal area placed 5° from the fovea, and therefore containing both rods and cones, the relation between critical frequency and log I shows two clearly separated sections. At the lower intensities the relation is sigmoid and reaches an upper level at about 10 cycles per second, which is maintained for 1.25 log units, and is followed by another sigmoid relationship at the higher intensities similar to the one given by the rod-free area alone. These two parts of the data are obviously separate functions of the rods at low intensities and of the cones at high intensities. This is further borne out by similar measurements made with retinal areas 15° and 20° from the fovea where the ratio of rods to cones is anatomically greater than at 5°. The two sections of the data come out farther apart on the intensity scale, the rod portion being at lower intensities and the cone portion at higher intensities than at 5°. The general form of the relation between critical frequency and intensity is therefore determined by the relative predominance of the cones and the rods in the retinal area used for the measurements.     

A possible model for the electrical responses of frog rods during light and dark adaptation

A theory is presented which predicts the electrical responses of frog rods during light and dark adaptation. It is based upon the recent physiological studies. The central points in the theory are that: blocking particles released from rod disks block sodium channels; blocking particles are inactivated by the active transport across the disk membrane; energy spent in the transport is supplied with a light-dependent rate. There was agreement between the properties of real and model rods: the responses to flashes and 47 s pulses; the rate of change of potential after a pulse; frequency response characteristics at different mean illuminances.     

THE INFLUENCE OF LIGHT ADAPTATION ON SUBSEQUENT DARK ADAPTATION OF THE EYE

The course of dark adaptation of the human eye varies with the intensity used for the light adaptation which precedes it. Preadaptation to intensities below 200 photons is followed only by rod adaptation, while preadaptation to intensities above 4000 photons is followed first by cone adaptation and then by rod adaptation. With increasing intensities of preadaptation, cone dark adaptation remains essentially the same in form, but covers an increasing range of threshold intensities. At the highest preadaptation the range of the subsequent cone dark adaptation covers more than 3 log units. Rod dark adaptation appears in two types—a rapid and a delayed. The rapid rod dark adaptation is evident after preadaptations to low intensities corresponding to those usually associated with rod function. The delayed rod dark adaptation shows up only after preadaptation to intensities which are hundreds of times higher than those which produce the maximal function of the rods in flicker, intensity discrimination, and visual acuity. The delayed form remains essentially constant in shape following different intensities of preadaptation. However, its time of appearance increases with the preadaptation intensity; after the highest preadaptation, it appears only after 12 or 13 minutes in the dark. These two modes of rod dark adaptation are probably the expression of two methods of formation of visual purple in the rods after its bleaching by the preadaptation lights.     

Intracellular recordings from gecko photoreceptors during light and dark adaptation

Intracellular recordings were obtained from rods in the Gekko gekko retina and the adaptation characteristics of their responses studied during light and dark adaptation. Steady background illumination induced graded and sustained hyperpolarizing potentials and compressed the incremental voltage range of the receptor. Steady backgrounds also shifted the receptor's voltage-intensity curve along the intensity axis, and bright backgrounds lowered the saturation potential of the receptor. Increment thresholds of single receptors followed Weber's law over a range of about 3.5 log units and then saturated. Most of the receptor sensitivity change in light derived from the shift of the voltage-intensity curve, only little from the voltage compression. Treatment of the eyecup with sodium aspartate at concentrations sufficient to eliminate the beta-wave of the electroretinogram (ERG) abolished initial transients in the receptor response, possibly indicating the removal of horizontal cell feedback. Aspartate treatment, however, did not significantly alter the adaptation characteristics of receptor responses, indicating that they derive from processes intrinsic to the receptors. Dark adaptation after a strongly adapting stimulus was similarly associated with temporary elevation of membrane potential, initial lowering of the saturation potential, and shift of the voltage-intensity curve. Under all conditions of adaptation studied, small amplitude responses were linear with light intensity. Further, there was no unique relation between sensitivity and membrane potential suggesting that receptor sensitivity is controlled at least in part by a step of visual transduction preceding the generation of membrane voltage change.     

Adaptation in the Ventral Eye of Limulus is Functionally Independent of the Photochemical Cycle, Membrane Potential, and Membrane Resistance

The early receptor potential (ERP), membrane potential, membrane resistance, and sensitivity were measured during light and/or dark adaptation in the ventral eye of Limulus. After a bright flash, the ERP amplitude recovered with a time constant of 100 ms, whereas the sensitivity recovered with an initial time constant of 20 s. When a strong adapting light was turned off, the recovery of membrane potential and of membrane resistance had time-courses similar to each other, and both recovered more rapidly than the sensitivity. The receptor depolarization was compared during dark adaptation after strong illumination and during light adaptation with weaker illumination; at equal sensitivities the cell was more depolarized during light adaptation than during dark adaptation. Finally, the waveforms of responses to flashes were compared during dark adaptation after strong illumination and during light adaptation with weaker illumination. At equal sensitivities (equal amplitude responses for identical flashes), the responses during light adaptation had faster time-courses than the responses during dark adaptation. Thus neither the photochemical cycle nor the membrane potential nor the membrane resistance is related to sensitivity changes during dark adaptation in the photoreceptors of the ventral eye. By elimination, these results imply that there are (unknown) intermediate process(es) responsible for adaptation interposed between the photochemical cycle and the electrical properties of the photoreceptor.     

A THEORY OF VISUAL INTENSITY DISCRIMINATION

1. A theory of visual intensity discrimination is proposed in terms of the photochemical events which take place at the moment when a photosensory system already adapted to the intensity I is exposed to the just perceptibly higher intensity I+ΔI. Unlike previous formulations this theory predicts that the fraction ΔI/I, after rapidly decreasing as I increases, does not increase again at high intensities, but reaches a constant value which is maintained even at the highest intensities. 2. The theory describes quantitatively the intensity discrimination data of Drosophila, of the bee, and of Mya. 3. With some carefully considered exceptions the intensity discrimination data of the human eye fall into two classes: those with small test areas or with red light, which form a single continuous curve describing the function of the retinal cones alone, and those with larger areas, and with white, orange, and yellow light, which form a double curve showing a clear inflection point, and represent the separate function of the rods at intensities below the inflection point and of the cones at intensities above it. 4. The theory describes all these data quantitatively by treating the rods and cones as two independently functioning photosensory systems in accordance with the well established duplicity idea. 5. In terms of the theory the data of intensity discrimination give critical information about the order of both the photochemical and dark reactions in each photosensory system. The reactions turn out to be variously monomolecular and bimolecular for the different animals.     

Activity of long-wavelength cones under scotopic conditions in the cyprinid fish Danio aequipinnatus

In carp (Cyprinus) and goldfish (Carassius), long-wavelength cones are reported to be active under scotopic conditions. Using the electroretinogram (ERG), we tested another cyprinid fish, Danio aequipinnatus, which contains A₁-based visual pigments and for which we had previously measured the spectral sensitivities of individual cones. Dark adaptation curves show a rod/cone break at about 45 min. When thoroughly dark-adapted, the spectral sensitivity function is broader than can be accounted for by self-screening of rhodopsin, but it can be modeled by an additive combination of rods and the 560-nm cones. Dim, red background light causes adaptation of rods and a broadening of the spectral sensitivity function, which can be simulated by increasing the proportion of cones in the model. Brighter red backgrounds adapt the 560-nm cones. Because of the effect of red adapting lights, the ERG evidence for the participation of long-wavelength cones close to visual threshold appears to be different in Danio than in the goldfish Carassius. Accepted: 14 June 1997     

Cyclic GMP levels and membrane current during onset, recovery, and light adaptation of the photoresponse of detached frog photoreceptors

We have used a preparation of isolated, intact rod photoreceptors to correlate the effects of flash illumination on the intracellular cyclic GMP content and the membrane current. We find that the recovery of cyclic GMP levels after brief flash illumination requires approximately twice as much time as the recovery of the membrane current. In contrast, the subsecond kinetics of the cyclic GMP response to light are faster than the kinetics of membrane current suppression. Both cyclic GMP and the membrane current show graded responses to a wide range of flash intensities; however, in a low Ca2+-Ringer's solution, dim flashes can trigger a decrease in cyclic GMP concentration with no corresponding decrease in membrane current. These results suggest that either other factors can regulate the membrane current, or that measurements of total cellular cyclic GMP do not accurately reflect dynamic changes in cyclic GMP concentration in the vicinity of the light-regulated channel. Changes in cyclic GMP concentration in the presence of background illumination exhibit adaptational behavior similar to that observed in a light-adapted photoresponse: acceleration in the response kinetics and a decrease in response amplitude. That this result is observed in rods depleted of internal Ca2+ suggests a Ca2+-independent mechanism by which background illumination can accelerate the cyclic GMP response.     

Control of Retinal Sensitivity : III. Lateral Interactions at the Inner Plexiform Layer

Both the "on" and the "on-off" ganglion cells in the mudpuppy retina generate graded responses over a narrow range of log test intensities. Sustained full field or surround backgrounds change the range of center log test intensities that elicits the graded response for both cell types. The on-off, but not the on ganglion cells are further affected by moving or flashing surround backgrounds. These cells are hyperpolarized, threshold is elevated, and the entire graded range of response is elicited by a higher range of log center test intensities. Depolarizing activity is elicited in amacrine cells by moving backgrounds that affect the on-off ganglion cells, but bipolar activity is unaffected. These results suggest that the amacrine cells at the inner plexiform layer mediate a third stage of sensitivity control in the retina, increasing threshold for response to change specifically in the on-off ganglion cells.     

Light adaptation in turtle cones. Testing and analysis of a model for phototransduction.

Light adaptation in cones was characterized by measuring the changes in temporal frequency responses to sinusoidal modulation of light around various mean levels spanning a range of four log units. We have shown previously that some aspects of cone adaptation behavior can be accounted for by a biochemical kinetic model for phototransduction in which adaptation is mediated largely by a sigmoidal dependence of guanylate cyclase activity on the concentration of free cytoplasmic Ca2+, ([Ca2+]i) (Sneyd and Tranchina, 1989). Here we extend the model by incorporating electrogenic Na+/K+ exchange, and the model is put to further tests by simulating experiments in the literature. It accounts for (a) speeding up of the impulse response, transition from monophasic to biphasic waveform, and improvement in contrast sensitivity with increasing background light level, I0; (b) linearity of the response to moderate modulations around I0; (c) shift of the intensity-response function (linear vs. log coordinates) with change in I0 (Normann and Perlman, 1979); the dark-adapted curve adheres closely to the Naka-Rushton equation; (d) steepening of the sensitivity vs. I0 function with [Ca2+]i fixed at its dark level, [Ca2+]i dark; (Matthews et al., 1988, 1990); (e) steepening of the steady-state intensity-response function when [Ca2+]i is held fixed at its dark level (Matthews et al., 1988; 1990); (f) shifting of a steep template saturation curve for normalized photocurrent vs. light-step intensity when the response is measured at fixed times and [Ca2+]i is held fixed at [Ca2+]i dark (Nakatani and Yau, 1988). Furthermore, the predicted dependence of guanylate cyclase activity on [Ca2+] closely matches a cooperative inhibition equation suggested by the experimental results of Koch and Stryer (1988) on cyclase activity in bovine rods. Finally, the model predicts that some changes in response kinetics with background light will still be present, even when [Ca2+]i is held fixed at [Ca2]i dark.     

Receptive fields of visual cortical neurons during changes in parameters of photic stimulation in cats

Spatial excitability contours in receptive fields of visual cortical neurons during changes in the physical and physiological parameters of photic stimulation were investigated in acute experiments on immobilized cats under conditions of dark, mesopic, and low photopic adaptation. With the change from dark to low mesopic adaptation the shape and size of the receptive fields detected by testing with flashes of constant intensity are unchanged, but with the transition to low photopic adaptation the receptive field becomes long and very narrow in 72% of cases, and the acuity of its orientational and directional tuning becomes much sharper. Against an unchanged background illumination, loss of brightness of the test light slit leads to narrowing of the measurable receptive field. Excitability contours of the receptive field estimated on the basis of absolute threshold of the cell response and level of intensity necessary to obtain the same number of spikes in the response become much narrower as the threshold criterion rises and during dark adaptation. Reactivity contours of the receptive field in response to stimulation of physiologically equal intensities (equal to the increase in threshold) under conditions of photopic adaptation also are much narrower than reactivity contours under conditions of dark adaptation. Evaluation of receptive fields with allowance for the possible contribution of effects of light scatter on the screen and in the ocular media showed that in most cases their size cannot be explained by these phenomena.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 12, No. 2, pp. 115–123, March–April, 1980.     

The contribution of single and double cones to spectral sensitivity in budgerigars during changing light conditions

Bird colour vision is mediated by single cones, while double cones and rods mediate luminance vision in bright and dim light, respectively. In daylight conditions, birds use colour vision to discriminate large objects such as fruit and plumage patches, and luminance vision to detect fine spatial detail and motion. However, decreasing light intensity favours achromatic mechanisms and eventually, in dim light, luminance vision outperforms colour vision in all visual tasks. We have used behavioural tests in budgerigars (Melopsittacus undulatus) to investigate how single cones, double cones and rods contribute to spectral sensitivity for large (3.4°) static monochromatic stimuli at light intensities ranging from 0.08 to 63.5 cd/m². We found no influences of rods at any intensity level. Single cones dominate the spectral sensitivity function at intensities above 1.1 cd/m², as predicted by a receptor noise-limited colour discrimination model. Below 1.1 cd/m², spectral sensitivity is lower than expected at all wavelengths except 575 nm, which corresponds to double cone function. We suggest that luminance vision mediated by double cones restores visual sensitivity when single cone sensitivity quickly decreases at light intensities close to the absolute threshold of colour vision.     

The Frequency-Response Electroretinogram Distinguishes Cone and Abnormal Rod Function in rd12 Mice

Early studies on Rpe65 knockout mice reported that remaining visual function was attributable to cone function. However, this finding has been challenged more and more as time has passed. Electroretinograms (ERGs) showed that rd12 mice, a spontaneous animal model of RPE65 Leber’s congenital amaurosis, had sizeable photopic responses. Unfortunately, the recorded ERG waveform was difficult to interpret because of a remarkably delayed peak-time, which resembles a rod response more than a cone response. Here, we compare flicker ERGs in animals with normal rod and cone function (C57BL/6J mice), pure rod function (cpfl5 mice), and pure cone function (Rho^-/- mice) under different adaptation levels and stimulus intensities. These responses were then compared with those obtained from rd12 mice. Our results showed that normal rods respond to low frequency flicker (5 and 15 Hz) and that normal cones respond to both low and high frequency flicker (5–35 Hz). As was seen in cpfl5 mice, rd12 mice had recordable responses to low frequency flicker (5 and 15Hz), but not to high frequency flicker (25 and 35 Hz). We hypothesize that abnormal rods may be the source of residual vision in rd12 mice, which is proved correct here with double mutant rd12mice. In this study, we show, for the first time, that frequency-response ERGs can effectively distinguish cone- and rod-driven responses in the rd12 mouse. It is another simple and valid method for evaluating the respective contributions of retinal rods and cones.