In vivo studies of signaling in rod pathways of the mouse using the electroretinogram.

PURPOSE: (a) To examine the possibility that there is a threshold in the synaptic mechanism linking rods to rod bipolar cells that can reduce the transmission of continuous noise from the rods without blocking the transmission of any significant proportion of single-photon responses. (b) To estimate the level of this threshold and the amplitude of the continuous noise which it can serve to reduce. (c) To identify the location of the threshold mechanism in the rod to rod bipolar cell pathway. METHODS: Corneal electroretinogram recordings were made from dark-adapted mice anesthetized with ketamine/xylazine after inner-retinal components had been suppressed to isolate PII, the response of depolarizing bipolar cells. Suppression was achieved by intravitreal injections of GABA, TTX, or in Cx36 KO animals by crushing the optic nerve and waiting for ganglion cells to degenerate. RESULTS: All energy-scaled records of isolated PII obtained with ganzfeld stimuli that gave rise to much less than one photoisomerization (R*) per rod (0.01-0.2 R*/rod), had an essentially identical waveform. Stronger stimuli caused a reduction in the peak amplitude of energy-scaled records (saturation) and stimuli strong enough to produce multiple isomerizations in individual rods resulted in a shortening of the response latency and an increase of the energy-scaled amplitude at early times (supralinearity). The shape of the rising edge of isolated PII changed with flash energy in a way that was consistent with the existence of a synaptic threshold whose level was less than one tenth of the amplitude of single-photon signals and a continuous noise whose rms amplitude was even less than this. However, when measured at the time of the peak, the amplitude of PII increased linearly in proportion to stimulus energy from the very lowest levels up to the point where there was, on average, 0.2 R*/rod. CONCLUSIONS: There is a threshold nonlinearity operating at the output of the rod to rod bipolar cell synapse that can usefully reduce the transmission of continuous rod noise without significantly affecting the transmission of single-photon signals. This nonlinearity does not affect the overall linear function of the rod pathway at levels at which it is effectively operating in a photon-counting mode.

The optic nerve head component of the monkey's (Macaca mulatta) multifocal electroretinogram (mERG).

To search for an optic nerve head component (ONHC) in the monkey's (Macaca mulatta) multifocal electroretinogram (mERG), mERGs from three animals were recorded with different electrode configurations. A component with a latency that varied with distance from the optic nerve head was easily identified by eye in recordings from the speculum of a Burian-Allen electrode referenced to a DTL on the unstimulated eye. This component was reasonably well isolated by subtracting a weighted version of a Burian-Allen bipolar recording or by employing the extraction algorithm of Sutter and Bearse (1999, Vision Research, 39, 419-436). The waveform of this component resembles the ONHC reported for the human mERG.

The photopic negative response of the flash electroretinogram in primary open angle glaucoma.

PURPOSE: To determine whether the photopic negative response (PhNR) of the electroretinogram (ERG) is reduced in patients with primary open angle glaucoma (POAG). METHODS: ERGs were recorded with DTL electrodes from 62 normal subjects (16 to 82 years), 18 POAG patients (47 to 83 years) and 7 POAG suspects (46 to 73 years) to brief flashes (<6 ms), and also in a few subjects to long (200 ms) red, full-field ganzfeld flashes delivered on a rod-saturating blue background. At the time of ERG measurements, the intraocular pressures of most of the patients were controlled medically. Visual field sensitivities were measured with the Humphrey C24-2 threshold test and optic nerve head cup-to-disc ratio (C/D) was determined by binocular indirect ophthalmoscopy. RESULTS: ERGs of normal subjects contained a slow negative potential following the a- and b-waves, the PhNR, that increased slightly in latency with age. The a- and b-wave amplitudes and implicit times of POAG patients were similar to age-matched controls. In contrast, their PhNRs were small or virtually absent. PhNR amplitudes were reduced even when visual sensitivity losses were small, and were correlated significantly (P < 0.05) with mean deviation (MD), corrected pattern SD (CPSD), and C/D across the population of POAG patients whose MD losses ranged from 1 to 13 dB, CPSDs from 0 to 11 dB and C/Ds from 0.6 to 0.9. PhNRs of most POAG suspects also were small. CONCLUSIONS: PhNR amplitudes in POAG patients are smaller than those of normal subjects. PhNR amplitudes are reduced when visual field sensitivity losses are mild and become even smaller as sensitivity losses increase. There is a potential role for the PhNR in early detection and possibly in monitoring the progression of glaucomatous damage.

The uniform field and pattern ERG in macaques with experimental glaucoma: removal of spiking activity.

PURPOSE: To determine whether the uniform field and pattern ERGs that are reduced in macaque eyes with experimental glaucoma have the same inner-retinal origins. METHODS: ERGs were recorded from 14 anesthetized adult macaques using DTL electrodes. Six monkeys had laser-induced experimental glaucoma, and two others received intravitreal injections of tetrodotoxin (TTX, 6 microM) to block spiking activity of inner-retinal neurons. The remaining 6 animals were normal. Uniform fields and grating patterns (0.1-3 cpd) were square-wave modulated at 1.7 Hz (transient) and 8 Hz (steady state). The test field (42 degrees x 32 degrees) had a mean luminance of 44 cd/m2 and a contrast of 10% to 82%. RESULTS: In normal eyes transient ERGs to uniform fields contained photopic negative responses (PhNR) after the b-wave and after the d-wave. Transient pattern electroretinograms (PERGs) at each contrast reversal showed positive (P50) potentials followed by negative (N95) potentials of time course similar to that of the PhNR. The PhNR and N95 were greatly reduced or eliminated by experimental glaucoma and by TTX. Summing responses to luminance increments and decrements of the uniform field could simulate the PERG to low spatial frequency stimuli. Further, the PERG responses to high spatial frequencies were similar to the simulation in shape but slightly delayed in time. Experimental glaucoma and TTX had similar effects on the N95 of the simulated PERG as to those on the actual PERG. However, P50 was more reduced by experimental glaucoma than by TTX, indicating a nonspiking contribution to P50. For the steady state condition, the uniform field ERG, the simulated PERG, and the actual PERG all were affected by experimental glaucoma and TTX, indicating that they contained contributions from the spiking activity of ganglion cells. CONCLUSIONS: The changes in the uniform field and PERG responses produced by experimental glaucoma are related and are largely a consequence of reduced spiking activity of ganglion cells and their axons. These findings raise the possibility that the uniform field ERG could serve as a useful alternative to the PERG in the assessment of clinical glaucomatous neuropathy.

Dynamic random noise shrinks the twinkling aftereffect induced by artificial scotomas.

Physiological alterations in cortical neurons are induced during adaptation to an artificial scotoma, a small homogeneous patch within a dynamic random noise or patterned background. When the dynamic noise is replaced by an equiluminant gray background, a twinkling aftereffect can be seen in the location of the artificial scotoma. Following binocular adaptation, we discovered that the perceived size of the twinkling aftereffect was dramatically smaller than the inducing artificial scotoma. Dichoptic adaptation induced shrinkage in the twinkling aftereffect that was similar to that found after binocular adaptation, suggesting that the twinkling aftereffect and its shrinkage both have cortical origins. We speculate that this perceptual shrinkage may reflect the interaction between two cortical mechanisms: a twinkling aftereffect mechanism that spreads throughout the artificial scotoma, and a filling-in mechanism that has a greater influence at the edges of the artificial scotoma and spreads inwards.

Effects of experimental glaucoma in macaques on the multifocal ERG. Multifocal ERG in laser-induced glaucoma.

Multifocal ERGs (MERGs) of 5 adult monkeys (Macaca mulatta) with inner retinal defects caused by laser-induced glaucoma were compared to MERGs from 3 monkeys with inner retinal activity suppressed pharmacologically. MERGs were recorded with DTL fiber electrodes from anesthetized monkeys. Stimuli consisted of 103 equal size hexagons within 17 degrees of the fovea. Stimuli at each location passed through a typical VERIS m-sequence of white (200 cd/m2) and black (12 cd/m2) presentations. In animals with laser-induced glaucoma, visual field sensitivity was assessed by static perimetry using the Humphrey C24-2 full-threshold program modified for animal behavior. Inner retinal (amacrine and ganglion cell) activity was suppressed by intravitreal injection of TTX (4.7-7.6 microM) and NMDA (1.6-5 mM). In normal eyes the first order response (1st order kernel) was larger and more complex, with more distinct oscillations (>60 Hz) in central than in peripheral locations. The 2nd order kernel also was dominated by oscillatory activity. There were naso-temporal variations in both kernels. Pharmacological suppression of inner retinal activity reduced or eliminated the oscillatory behavior, and naso-temporal variations. The 1st order kernel amplitude was increased most and was largest at the fovea. Removed inner retinal responses also were largest at the fovea. The 2nd order kernel was greatly reduced at all locations. In eyes with advanced glaucoma, the effects were similar to those produced by suppressing inner retinal activity, but the later portion of the 1st order kernel waveform was different, lacking a dip after the large positive wave. Visual sensitivity losses and MERG changes both increased over the timecourse of glaucoma, with changes in the MERG being more diffusely distributed across the visual field. We conclude that 1st and 2nd order responses of the primate MERG can be identified that originate from inner retina and are sensitive indicators of glaucomatous neuropathy.

Evidence for a ganglion cell contribution to the primate electroretinogram (ERG): effects of TTX on the multifocal ERG in macaque.

To assess the contribution of spiking inner retinal neurons to the multifocal electroretinogram (ERG), recordings were made from four monkeys (Macaca mulatta) before and after intravitreal injections of tetrodotoxin (TTX). TTX blocks all sodium-based action potentials and thus terminates spiking activity of amacrine and ganglion cells. TTX eliminated a large component from the control responses, and this TTX-sensitive component was present as early as 10 ms after the stimulus. Before injection with TTX, the 103 focal ERG responses varied in waveform across the retina. After TTX, the response waveforms were largely independent of retinal position, indicating that it was primarily the TTX-sensitive component of the control response that was dependent upon retinal location. Given that retinal ganglion cells compose a sizable proportion of the retinal elements that produce action potentials, it is likely that part of the TTX-sensitive component is due to the spiking activity of these cells. Further, the systematic change in waveform of the TTX-sensitive component with distance from the optic nerve head suggests that part of the TTX-sensitive component may originate from the activity of the ganglion cell axons. Based on these findings, there is reason to be optimistic that the multifocal technique can be employed to study the effects of glaucoma and other diseases that affect the inner retina.

The photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma.

PURPOSE: To investigate the photopic flash electroretinograms (ERGs) of macaque monkeys in which visual field defects developed as a consequence of experimental glaucoma. METHODS: Unilateral experimental glaucoma was induced in 10 monkeys by argon laser treatment of the trabecular meshwork. Visual field sensitivity was assessed behaviorally by static perimetry. Photopic ERGs were recorded to brief- (< or = 5 msec) and long-duration (200 msec) red ganzfeld flashes on a rod-suppressing blue-adapting background. Electroretinograms were recorded in four other monkeys, after intravitreal injection of tetrodotoxin (TTX; 3.8-8 p.M) to suppress action potentials of retinal ganglion and amacrine cells, and in six normal adult human subjects. RESULTS: Experimental glaucoma removed a cornea-negative response, the photopic-negative response (PhNR), from the ERG. The PhNR in control eyes was maximal approximately 60 msec after a brief flash, 100 msec after onset, and 115 msec after offset of the long-duration stimulus. The PhNR in experimental eyes was greatly reduced when the mean deviation of the visual field sensitivity was as little as -6 dB. As visual sensitivity declined further, the PhNR was reduced only slightly more. The a- and b-waves were unchanged, even when sensitivity decreased by more than 16 dB. Tetrodotoxin also selectively reduced the PhNR. The PhNR was observed in normal human ERGs. CONCLUSIONS: The cornea-negative PhNR of the photopic ERG depends on spiking activity and is reduced in experimental glaucoma when visual sensitivity losses are still mild. The PhNR most likely arises from retinal ganglion cells and their axons, but its slow timing raises the possibility that it could be mediated by glia. Regardless of the mechanism of its generation, the PhNR holds promise as an indicator of retinal function in early glaucomatous optic neuropathy.

The precision of velocity discrimination across spatial frequency.

The precision of velocity coding for moving stimuli of different spatial frequencies was assessed by measuring velocity discrimination thresholds for a 1-c/deg grating paired with a grating whose spatial frequency ranged from 0.25 to 4 c/deg and for grating pairs of the same spatial frequency (0.25, 1, and 4 c/deg). The gratings always moved upward, with velocities ranging from 0.5 to 16 deg/sec. Velocity discrimination was as precise for stimuli that varied in spatial frequency by +/- 2 octaves (0.25 vs. 1 c/deg and 4 vs. 1 c/deg) as for stimuli of the same spatial frequency, for specific ranges of velocity that depended on the spatial and, therefore, the temporal frequencies of the stimuli. Compared with a 1-c/deg grating, the perceived velocity of 4-c/deg gratings was about 1.3 times faster and that of 0.25-c/deg gratings was about 1.3 times slower. Although these perceived velocity biases imply variation of velocity-signal processing among spatial frequency channels, the discrimination results indicate that the motion-sensing system can compare signals across different spatial frequency channels to make fine velocity discrimination within appropriate temporal frequency limits.

Stimulus uncertainty affects velocity discrimination.

Velocity discrimination thresholds were determined for 1 c/deg drifting gratings when uncertainty about the reference velocity was introduced by interleaving stimuli with different reference velocities from trial to trial. When drifting gratings with reference velocities spanning 4 octaves (1-16 deg/sec) were mixed randomly within a series of trials, the velocity discrimination threshold for a 4 deg/sec stimulus increased by more than a factor of 3. The threshold elevation decreased as the range of interleaved velocities was reduced from 4 to approx. 0.75 octaves, below which velocity interleaving had little effect. In contrast, when gratings that spanned a 4-octave range in spatial frequency were interleaved on successive trials, velocity discrimination for 4 deg/sec was essentially unaffected. Our results indicate that the psychophysical mechanisms underlying velocity discrimination are not spatial-frequency specific, but are turned to the velocity or speed of the stimulus.

Dissecting the dark-adapted electroretinogram.

Although gross recordings of the ganzfeld flash-evoked electroretinogram (ERG) can potentially provide information about the activity of many, if not all, retinal cell types, it is necessary to dissect the ERG into its components to realize this potential fully. Here we describe various procedures that have been used in intact mammalian eyes to identify and characterize the contributions to the dark-adapted ERG of different cells in the retinal rod pathway. These include (1) examination of the very early part of the response to a flash (believed to reflect directly the photocurrent of rods), (2) application of high-energy probe flashes to provide information about the underlying rod photoreceptor response even when this component is obscured by the responses of other cells, (3) pharmacological suppression of responses of amacrine and ganglion cells to identify the contribution of these cells and to reveal the weaker responses of bipolar cells, (4) use of pharmacological agents that block transmission of signals from rods to more proximal neurons to separate responses of rods from those of later neurons, (5) examination of the ERG changes produced by ganglion-cell degeneration or pharmacological block of nerve-spike generation to identify the contribution of spiking neurons, (6) modeling measured amplitude-energy functions and timecourse of flash responses and (7) using steady backgrounds to obtain differential reductions in sensitivity of different cell types. While some of these procedures can be applied to humans, the results described here have all been obtained in studies of the ERG of anaesthetized cats, or macaque monkeys whose retinas are very similar to those of humans.

Effects of background light on the human dark-adapted electroretinogram and psychophysical threshold.

We compared the effects of background light on the sensitivities of two components of the human electroretinogram, the cornea-negative scotopic threshold response (STR) and the cornea-positive PII (beta wave), as well as on the psychophysical sensitivity in a ganzfeld. The background illuminance necessary to reduce the STR (an inner retinal signal) measurably was approximately five times greater than that needed to raise the psychophysical threshold. A background illuminance at least 1 log unit greater still was needed to reduce PII (a signal-reflecting activity of bipolar cells). These findings suggest (1) that the weakest backgrounds that reduce retinal sensitivity have their effect at a site that is proximal to the bipolar cells, a site that involves amacrine or ganglion cells, and (2) that very weak backgrounds have their effect on visual sensitivity at a site more proximal than the scotopic threshold response generator and perhaps more central than the retina.

Photoreceptor and bipolar cell contributions to the cat electroretinogram: a kinetic model for the early part of the flash response.

The time course of the initial negative wave of the flash electroretinogram of the dark-adapted cat has been found to be critically dependent of contributions from cells of the inner retina, not only for very low-intensity flashes for which the negative scotopic threshold response is dominant but also when the stimulus is sufficiently intense for the rods themselves to contribute directly to the electroretinogram. However, if the inner-retinal responses are blocked pharmacologically or are suppressed by a steady adapting background, the initial negative wave of the remaining electroretinogram (the alpha wave) can be explained as the sum of photoreceptor and bipolar-cell components that can be modeled as described by Lamb and Pugh [J. Physiol. (London) 449, 717 (1992)] and Robson and Frishman [Vis. Neurosci. 12, 837 (1995)], respectively.

Temporal-contrast discrimination and its neural correlates.

Reported differences in neuronal contrast processing between the parallel magnocellular (M) and parvocellular (P) visual pathways invite the hypothesis that contrast discrimination in the human visual system is more sensitive at low contrasts and less sensitive at high contrasts, for stimuli modulated at high compared with low temporal frequencies. In the present study, an edgeless temporally modulated uniform field was selected as the stimulus for psychophysical contrast discrimination, and contrast-increment thresholds for pedestal contrasts ranging from 5.5% to 78.2% were determined with a temporal two-alternative forced-choice staircase procedure. The increment thresholds for five normal subjects were adequately fit by power functions with exponents that shifted continuously from about 0.5 (square-root-law behavior) to about 1.0 (Weber's-law behavior) as stimulus temporal frequency increased from 1 to 30 Hz. A neural simulation, with the use of published contrast-response functions of magnocellular and parvocellular neurons, adjusted with an estimate of response variance, produced two distinct 'neural increment-threshold functions' that were similar to the psychophysical results obtained at the highest and the lowest temporal frequencies, respectively. A shift from a relatively more noise-limited neural mechanism to one whose response is predominantly determined by gain is suggested to account for the change of the contrast-increment-threshold function with increasing temporal frequency.

The scotopic electroretinogram of macaque after retinal ganglion cell loss from experimental glaucoma.

PURPOSE: This study describes the dark-adapted electroretinograms (ERGs) of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension. METHODS: Monocular experimental glaucoma was produced by argon laser trabeculoplasty, and visual fields were assessed with behavioral static perimetry. Electroretinographic responses to brief ganzfeld flashes under fully dark-adapted conditions were recorded using DTL fiber electrodes in anesthetized animals. The authors quantified retinal layer thickness and cell loss in 1-micron radial sections and inspected optic nervous under the light microscope. RESULTS: At the lowest intensities, a sensitive negative component of the scotopic ERG, which normally peaks approximately 200 msec after stimulus onset, was present in the control eyes but was reduced greatly or was virtually absent in the experimental eyes of monkeys with severe visual field loss. A previously unreported sensitive positive component of the scotopic ERG remained in both eyes. In the control eyes, the positive component gave rise to a sharp peak approximately 120 msec after stimulus onset, but in the experimental eyes, because of the absence of the more delayed sensitive negative potential, it was sustained, lasting as long as 700 msec. Scotopic a- and b-waves and oscillatory potentials in the experimental eyes were not consistently different from control eyes. Ganglion cell and optic nerve loss in the experimental eyes was substantial, and there was little other obvious retinal damage. CONCLUSIONS: A sensitive negative component is reduced or absent from the dark-adapted ERGs of macaque monkeys with severe visual field defects and substantial retinal ganglion cell loss as a consequence of long-standing ocular hypertension.

Response linearity and kinetics of the cat retina: the bipolar cell component of the dark-adapted electroretinogram.

The electroretinogram (ERG) of the dark-adapted cat eye in response to brief ganzfeld flashes of a wide range of intensities was recorded after intravitreal injection of n-methyl DL aspartate (NMDLA, cumulative intravitreal concentration of 1.3-3.9 mM) to suppress inner-retinal components, and after intravitreal DL or L-2-amino-4-phosphonobutyric acid (DL-APB, 1-3 mM; L-APB, 1.2 mM) and 6-cyano-7-nitroquinoxaline-2,3 dione (CNQX, 40-60 microM), to suppress all post-receptoral neuronal responses. Rod PII, the ERG component arising from rod bipolar cells, was derived by subtracting records obtained after APB and CNQX from post-NMDLA records. When we measured the derived response at fixed times after the stimulus, we found that PII initially increased in proportion to stimulus intensity without any sign of a threshold. The leading edge of PII at early times after the stimulus, when the response was still small, was well described by V(t) = kI(t-td)5 where k is a constant, I is the intensity of the stimulus, and td is a brief delay of about 3 ms. Correspondingly, the time for the response to rise to an arbitrary small criterion voltage Vcrit was adequately fitted by tcrit = td + (Vcrit/kI)1/5. The time course of the leading edge of the PII response can be interpreted to indicate that the mechanism generating PII introduces three stages of temporal integration in addition to the three stages that are provided by the mechanism of the rod photoreceptors. This finding is consistent with the operation within the rod bipolar cell of a G-protein cascade similar to that in the rods.

Evidence for two sites of adaptation affecting the dark-adapted ERG of cats and primates.

The present study compared the effects of full-field steady adapting backgrounds on the sensitivity of the scotopic threshold response (STR) of the dark-adapted ERG and scotopic PII (b-wave and d.c.-component) to Ganzfeld flashes in cats (n = 4), macaque monkeys (n = 2), and one human subject. In cats, the sensitivity of the STR was reduced by a factor of 2 by backgrounds that were 500 times weaker than backgrounds reducing PII; and for the primates, the STR was reduced by backgrounds almost 100 times weaker than those reducing PII. Since the STR is generated more proximally in the retina than PII, these results provide evidence for proximal and more distal retinal sites of postreceptoral light adaptation. A practical implication is that dim scattered room light can remove the STR from the ERG while hardly affecting PII.

Light-evoked changes in [K+]o in proximal portion of light-adapted cat retina.

1. The M-wave is a light-adapted response of proximal retina consisting of phasic negative field potentials at light onset and offset that are spatially tuned for small stimuli. We measured light-dependent changes in extracellular K+ concentration ([K+]o) in proximal retina to investigate the hypothesis that the M-wave originates from Müller cell responses to changes in [K+]o. 2. Extracellular field potentials, and changes in [K+]o evoked in response to circular spots of light flashed on steady backgrounds, were recorded with double-barreled K(+)-sensitive electrodes placed in the retina at different depths. 3. Increases in [K+]o during illumination and at light offset were maximal in proximal retina, with the On [K+]o increase located more proximally than the Off increase. The [K+]o increase during illumination consisted of a phasic and sustained response, whereas the Off [K+]o increase was predominantly phasic. The spatial tuning of the [K+]o increases was similar to the tuning of the field potentials. 4. The Off-field potential was larger than the On potential; it tended to be maximal more distally and was more sharply localized in retinal depth. Stimulus-response characteristics of the field potentials were not altered by intravitreal tetrodotoxin (TTX; 3.8 microM) sufficient to block retinal ganglion cell action potentials. 5. There were no rod contributions to the proximal [K+]o increases and field potentials recorded at the background illuminations used in this study (9.5-11.5 log q.deg-2.s-1). 6. An intravitreal injection of L- or DL-2-amino-4-phosphonobutyric acid (APB; 1 mM) was used to block On-system neuronal responses in proximal retina and isolate Off-system responses. After APB the [K+]o response consisted of a sustained decrease in [K+]o during illumination followed by an overshoot at light offset, while the field potential was a sustained positive response at light onset followed by an initially phasic negative response at light onset followed by an initially phasic negative response at light offset. These responses retained spatial tuning. To isolate the On-system components, the APB-isolated responses were subtracted from the controls. The [K+]o response now consisted of a sustained increase during illumination followed by an undershoot at light offset. The field potential was a sustained negative potential with an initial phasic peak that decayed at Off. Results with kynurenate (KYN; 5 mM) and (+/-)cis-2,3-piperidine (PDA; 5 mM) confirmed the sustained nature of the On component.(ABSTRACT TRUNCATED AT 400 WORDS)

Origin of negative potentials in the light-adapted ERG of cat retina.

1. The light-adapted diffuse-flash electroretinogram (ERG) in the cat exhibits two prominent negative components: a sustained negative potential during illumination and a negative-going OFF response. We investigated their intraretinal origins and found that the sustained component originates from the rod photoreceptors, whereas the OFF response represents a combination of the return to base line of the rod-receptor potential, the offset of PII (rod and cone), and a cone-dependent OFF response originating proximal to the photoreceptors at very high background levels. 2. The ERG, evoked in response to diffuse illumination of the light- and dark-adapted cat retina, was recorded between a chlorided silver wire in the vitreous and a plate behind the eye. Extracellular field potentials were recorded simultaneously with a microelectrode placed intraretinally at different retinal depths. 3. The sustained negative potential and the negative OFF response were not the M-wave ON and OFF responses of proximal retina, despite an overall resemblance in form and time course: 1) the M-wave was spatially tuned, whereas the ERG components were not; 2) tetrodotoxin (TTX) (3.8-microM vitreal concentration) did not alter the M-wave, but it reduced the ERG OFF response; 3) picrotoxin (0.14 mM, after TTX) enhanced the M-wave but did not affect the negative ERG; and 4) 2-amino-4-phosphonobutyric acid (APB; 0.95 mM) removed the M-wave ON response, and aspartate (43 mM) removed the M-wave OFF response, in addition, while the sustained negative potential persisted. 4. The sustained negative potential was not slow PIII, the neural retinal component of the c-wave, a Müller cell response to the photoreceptor-dependent light-evoked decrease in subretinal extracellular K+ concentration [( K+]o). Although Ba2+ (repeated injections of 4-5 mM), a K+ conductance blocker, eliminated slow PIII, it did not remove the sustained negative potential. We concluded that the sustained negative potential was a photoreceptor potential, and the spectral sensitivity of the response indicated that it arose from rods. 5. The contribution of the rod-receptor potential to the ERG depended on background illumination. It was a sustained potential for a range of backgrounds near and 1 or 2 log units above the illumination that saturates rod-driven responses in cat (8.2 log quanta.deg-2.s-1). At lower background intensities, it appeared only as a dip between the b- and c-waves, the b-wave trough, which also was present in fully dark-adapted responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Light-evoked increases in [K+]o in proximal portion of the dark-adapted cat retina.

1. The scotopic threshold response (STR) and slow negative response are negative-going potentials in the dark-adapted electroretinogram (ERG) of the cat eye that originate proximal to the photoreceptors and are present at threshold and with dim illuminations. The present paper examines the hypothesis that these events are associated with Müller cell responses to potassium released by proximal retinal neurons by measuring light-dependent changes in extracellular K+ concentration [( K+]o, in proximal retina. 2. Extracellular field potentials and changes in [K+]o, evoked in response to diffuse illumination of the dark-adapted retina, were recorded with a double-barreled K+-sensitive microelectrode placed in the retina at different depths. The vitreal ERG was recorded at the same time. 3. The dynamic range of the light-evoked increases in [K+]o, recorded in proximal retina from threshold to saturation, was strikingly similar to that of the STR and slow negative response. The threshold for the [K+]o increase was near that of the most sensitive ganglion cells, and the response saturated approximately 2.4 log units below rod saturation. Also, onset latencies and rates of rise for the increases in [K+]o and the field potentials in proximal retina followed similar functions of intensity. 4. The depth distribution of the light-evoked [K+]o increases resembled that of the STR. The increases in [K+]o were largest and fastest in proximal retina where the STR was largest. This was true both for very low intensity stimuli, below the threshold for PII (DC-component and b-wave) in distal retina, and for stimulus intensities near STR saturation, where PII (DC-component) was present. For stimuli of intensities near rod saturation, when the b-wave was present in distal retina, there was a small fast increase in [K+]o at light onset in distal retina and a slower increase in proximal retina. Both increases were truncated by spread of the large light-evoked decrease in [K+]o in subretinal space that is known to cause the c-wave in the ERG and slow PIII in neural retina. 5. The duration of the increases in [K+]o in proximal retina was more sustained than the proximal field potentials. In response to stimuli of 2-4 s, the field potential began to recover toward base line after about 300 ms, whereas the increases in [K+]o remained at maximal levels until stimulus offset.(ABSTRACT TRUNCATED AT 400 WORDS)