Dopamine is a light-adaptive signal that desensitizes the retina, while cannabinoids reportedly increase photosensitivity. The presynaptic membrane of goldfish retinal cones has dopamine D2 receptors and cannabinoid CB1 receptors. This work focused on whether dopamine D2 receptor agonist quinpirole and cannabinoid CB1 receptor agonist WIN 55212-2 (WIN) interacted to modulate voltage-dependent membrane currents of cones. A conventional patch-clamp method was used to record depolarization evoked whole-cell outward currents (Iout) and an inward calcium current (ICa) from the inner segment of cones in goldfish retinal slices. WIN had biphasic actions: low concentrations (<1 μM) increased the currents via Gs, while higher concentrations (>1 μM) decreased the currents via Gi/Go. Neither dopamine nor the D2 agonist quinpirole (1–20 μM) had a significant effect on either Iout or ICa. Quinpirole at 50 μM had a mild suppressive (∼20%) effect on Iout. However, quinpirole (<10 μM) completely blocked the enhancement of both currents seen with 0.7 μM WIN. The effect of quinpirole was blocked by sulpiride and by pertussis toxin, indicating that quinpirole was acting via a D2 receptor-Gi/o coupled mechanism. The suppressive action of 50 μM quinpirole (∼20%) was not additive with the suppressive effect of 3 μM WIN (∼40%). D2 agonists via Gi/o oppose the action of low concentrations of CB1 agonists acting via Gs to modulate cone membrane currents, suggesting a role in shaping the cone light response and/or sensitivity to changes in ambient light conditions. The nonadditive effect of high concentrations of WIN and quinpirole suggests that both decrease membrane currents via the same transduction pathway, Gi/Go protein kinase A (PKA).

Studies of color vision in marsupial mammals have been very limited. Two photoreceptor genes have been characterized from the tammar wallaby, but a third cone pigment was suggested by microspectrophotometric measurements on cone photoreceptors in two other species, including the fat-tailed dunnart, Sminthopsis crassicaudata. To determine the sequence and infer absorption maxima of the cone photoreceptor pigments of S. crassicaudata and the related stripe-faced dunnart (Sminthopsis macroura), we have used evolutionarily conserved sequences of the cone pigments of other species, including the tammar wallaby, to design primers to amplify the S. macroura and S. crassicaudata pigment sequences by the polymerase chain reaction (PCR) using genomic DNA or retinal cDNA as a template. These primers will be useful for amplifying cone opsin coding sequences from a variety of vertebrates. Amplified products were directly sequenced to determine gene structure and coding sequences. The inferred amino acid sequences of the cone visual pigments indicated that both species have middle-wave-sensitive (MWS) pigments with a predicted absorption maximum (λmax) at 530 nm, and ultraviolet-sensitive (UVS) pigments with a predicted λmax at 360 nm. The MWS pigments of the two species differ by two, and UVS by three amino acid positions. No evidence was obtained for a third cone pigment in either species.

Contrast encoding for sinusoidal modulations of luminance contrast was investigated by intracellular recording in the intact salamander retina. In what appears to be the first study of this kind for vertebrate bipolar cells, responses of the central receptive-field mechanism of cone-driven cells to modulation of 3 Hz were analyzed quantitatively via both signal averaging and a Fast Fourier Transform (FFT) while the retina was light adapted to 20 cd/m2. Depolarizing and hyperpolarizing bipolar cells showed very similar encoding. Both responded with sinusoidal waveforms whose amplitude varied linearly with modulation depths ranging up to 7–8%. The slope of the modulation/response curve was very steep in this range. Thus, the contrast gain was high, reaching values of 6–7, and the half-maximal response was achieved at modulations of 9% or less. At modulations above ∼15%, the responses typically showed strong compressive nonlinearity and the waveform was increasingly distorted. At maximum modulation, the higher harmonics of the FFT constituted about 30% of the amplitude of the fundamental. Measurements were also made for cones and horizontal cells. Both cell types showed predominantly linear responses and low contrast gain, in marked contrast to bipolar cells. These results suggest that the high contrast gain and strong nonlinearity of bipolar cells largely arise postsynaptic to cone transmitter release. Further experiments were performed to compare responses to contrast steps versus those to sinusoidal modulation. In the linear range, we show that the contrast gains of cones and horizontal cells are low and virtually identical for both steps and sinusoidal modulations. In bipolar cells, on the other hand, the contrast gain is about two times greater for steps than that for the 3-Hz sine waves. These results suggest that mechanisms intrinsic to bipolar cells act like a high-pass filter with a short time constant to selectively emphasize contrast transients over slower changes in contrast.

Conditioning human observers with an “artificial scotoma”—a small retinal area deprived of patterned stimulation within a larger area of dynamically textured noise—results in contractions and expansions of perceived space that are thought to reflect receptive-field changes among cells in the primary visual cortex (Kapadia et al., 1994). Here we show that one-dimensional counter-phase flickering grating patterns are also potent stimuli for producing artificial scotomata capable of altering three-element bisection ability analogous to those results reported earlier. Moreover, we found that the magnitude of the induced spatial distortions depends critically on the relative orientations of peri-scotomatous and test-stimulus spatial contrast. In addition, the perceptual distortions are found to be relatively short lived, decaying within 660 ms. The results support the hypothesis that artificial scotoma-induced perceptual distortions are generated by dynamic alteration of connection efficacy within a network linking cortical areas of similar orientation specificity, consistent with established anatomical and physiological results.

The mdxCv3 mouse is a model for Duchenne muscular dystrophy (DMD). DMD is an X-linked disorder with defective expression of the protein dystrophin, and which is associated with a reduced b-wave and has other electro- retinogram (ERG) abnormalities. To assess potential causes for the abnormalities, we recorded ERGs from pieces of isolated C57BL/6J and mdxCv3 mouse retinas, including measurements of transretinal and intraretinal potentials. The ERGs from the isolated mdxCv3 retina differ from those of control retinas in that they show reduced b-wave amplitudes and increased b-wave implicit times. Photovoltages obtained by recording across the photoreceptor outer segments of the retinas did not differ from normal, suggesting that the likely causes of the reduced b-wave are localized to the photoreceptor to ON-bipolar synapse. At a concentration of 50 μM, the glutamate analog DL-2-amino-4-phosphonobutyric acid (APB) blocks the b-wave component of the ERG, by binding to sites on the postsynaptic membrane. The On-bipolar cell contribution to the ERG was inferred by extracting the component that was blocked by APB. We found that this component was smaller in amplitude and had longer response latencies in the mdxCv3 mice, but was of similar overall time course. To assess the sensitivity of sites on the postsynaptic membrane to glutamate, the concentration of APB in the media was systematically varied, and the magnitude of blockage of the light response was quantified. We found that the mdxCv3 retina was 5-fold more sensitive to APB than control retinas. The ability of lower concentrations of APB to block the b-wave in mdxCv3 suggests that the ERG abnormalities may reflect alterations in either glutamate release, the glutamate postsynaptic binding sites, or in other proteins that modulate glutamate function in ON-bipolar cells.

We studied the cervico-ocular reflex (COR) alone and in combination with the optokinetic (OKN) reflex in head-fixed pigeons. We analyzed these responses in two behavioral conditions: (1) animals were hung in a harness (“resting” condition); and (2) animals were additionally submitted to a frontal airflow that provoked a flight posture (“flying” condition). In both conditions, cervical stimulation provoked a slow phase of very low gain (around 0.05) in the opposite direction to that of the stimulation and fast phases triggered near the head–body alignment in the same direction as the stimulation. The slow phase showed a phase lag of 20 deg at 0.5 Hz. The gain of the slow phase was not modified by the velocity, amplitude, or frequency of the stimuli. This gain was not changed by the presence of a fixed visual surround.

When cervical stimuli (0.05–0.5 Hz) were added to an optokinetic stimulation (30 deg/s) in the “resting” condition, the slow phase velocity (SPV) of the optokinetic reflex was modulated with a time course close to that produced by the cervico-ocular reflex alone. The SPV was alternately increased and decreased round the SPV level corresponding to the steady-state OKN. In the “flying” condition, optokinetic-cervical stimulation provoked an eye beating field and a strong SPV modulation synchronized with the position of the cervical stimulation. The number of nystagmic beats (OKN) and the amplitude and velocity of the fast phases were modulated in correlation with the SPV. Consequently, the optokinetic response was increased or decreased according to whether the cervical stimuli were in the reverse direction or in the same direction as the optokinetic stimulation, respectively.

These data are interpreted as an improvement of gaze stabilization by the COR. This mechanism is context dependent, since it is strongly reinforced during the flight.

It is implicit in many cone-specific ERG studies that the amplitude is proportional to the numbers of cones stimulated. The objective of these experiments was to test this idea by comparing ERGs obtained from different areas of the retina with histological data on cone-density distributions. The histology (Curcio et al., 1990) shows that the cumulative number of cones in the human retina increases exponentially with stimulus diameter between 0- and 40-deg eccentricity. L-, M-, and (L+M) cone-driven 30-Hz ERGs were obtained from a series of stimuli with one of the following configurations: (1) Circular stimuli of different angular subtense up to 70-deg diameter. (2) Annuli with 70-deg outer diameter but variable inner diameter. (3) Annuli of constant area but increasing eccentricity. Cone contrasts were equalized for each stimulus condition. The modulated and nonmodulated regions of the screen had the same mean hue and luminance. The data suggest that the L+M cone ERG amplitude increases with stimulus diameter in direct proportion to the estimated number of cones stimulated. Furthermore, the total L+M responses appear to be predicted from individual L and M responses by simple linear summation for both the disc and annular stimuli.

Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.

Glutamate receptor currents were examined in horizontal cells from cultured human retina using whole-cell recording procedures. Horizontal cells possess both AMPA and kainate receptors and both produce significant sustained currents. The kainate-induced current did not show significant desensitization and was not enhanced by concanavalin A. The sustained AMPA current was smaller than the kainate current, but the difference was almost entirely due to pronounced desensitization. The horizontal cell AMPA current was enhanced by cyclothiazide but not by PEPA, indicating the presence of the flip receptor variant. GYKI-52466 blocked the AMPA response (IC50 = 5 μM against 100 μM AMPA) but also blocked the kainate response (IC50 = 45 μM against 100 μM kainate). The diversity of glutamate receptors in human horizontal cells suggests that synaptic input to these neurons may be multiplexed through both kainate and AMPA channels.

Why photoreceptors turn over a portion of their photoreceptive membrane daily is not clear; however, failure to do so properly leads to retinal degeneration in vertebrates and invertebrates. Little is known about the molecular mechanisms that regulate shedding and renewal of photoreceptive membrane. Photoreceptor cells in the lateral eye of the horseshoe crab Limulus turn over their photoreceptive membrane (rhabdom) in a brief, synchronous burst in response to dawn each morning. Transient rhabdom shedding (TRS), the first phase of rhabdom turnover in Limulus, is triggered by dawn, but requires a minimum of 3–5 h of overnight priming from the central circadian clock (Chamberlain & Barlow, 1984). We determined previously that the clock primes the lateral eye for TRS using the neurotransmitter octopamine (OA) (Khadilkar et al., 2002), and report here that OA primes the eye for TRS through a Gs-coupled, adenylate cyclase (AC)/cyclic adenosine 3′,5′-monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) signaling cascade. Long-term intraretinal injections (6–7 h @ 1.4 μl/min) of the AC activator forskolin, or the cAMP analogs Sp-cAMP[S] and 8-Br-cAMP primed the retina for TRS in eyes disconnected from the circadian clock, and/or in intact eyes during the day when the clock is quiescent. This suggests that OA primes the eye for TRS by stimulating an AC-mediated rise in intracellular cAMP concentration ([cAMP]i). Co-injection of SQ 22,536, an AC inhibitor, or the PKA inhibitors H-89 and PKI (14-22) with OA effectively antagonized octopaminergic priming by reducing the number of photoreceptors primed for TRS and the amount of rhabdom shed by those photoreceptors compared with eyes treated with OA alone. Our data suggest that OA primes the lateral eye for TRS in part through long-term phosphorylation of a PKA substrate.

Physiological properties of ligand-activated currents were characterized for morphologically identified AII amacrine cells in the rabbit retina by using whole-cell recordings in a superfused retina slice preparation. The AII amacrine cells were identified based on their distinct narrow-field, bistratified morphology. In the present study, the whole-cell recordings from AII amacrine cells synaptically isolated from presynaptic influences demonstrated the presence of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptors, but no kainate receptors. The presence of only AMPA receptors on rabbit AII amacrine cells is in contrast to an earlier study on rabbit AII amacrine cells by Bloomfield and Xin (2000), but consistent with previous studies on rat AII amacrine cells. In addition, NMDA (N-methyl-D-aspartate) -activated currents blocked by the NMDA antagonist D-AP7 (D-2-amino-7-phosphonoheptanoic acid) were found on the AII amacrine cells. These most likely extrasynaptic NMDA-activated currents were attenuated by the presence of Co2+ interacting with Mg2+ and Ca2+ as they competed for divalent cation-binding sites within the NMDA channel. AII amacrine cells also possessed GABA (γ-aminobutyric acid) -activated currents that were unaffected by the GABAC receptor antagonist TPMPA (1,2,5,6-tetrahydropyridine-4-yl methylphosphinic), but were completely blocked by the GABAA antagonist bicuculline. This indicates that the major inhibitory inputs were mediated by only GABAA receptors located directly on the AII amacrine cells. Furthermore, although the AII amacrine cells were glycinergic amacrine cells, they also possessed glycine-activated currents that may be mediated by autoreceptors.

We used suction-pipette recording and fluo-4 fluorescence to study light-induced Ca2+ release from the visible double cones of zebrafish. In Ringer, light produces a slow decrease in fluorescence which can be fitted by the sum of two decaying exponentials with time constants of 0.5 and 3.8 s. In 0Ca2+–0Na+ solution, for which fluxes of Ca2+ across the outer segment plasma membrane are greatly reduced, light produces a slow increase in fluorescence. Both the decrease and increase are delayed after incorporation of the Ca2+ chelator BAPTA, indicating that both are produced by a change in Ca2+. If the Ca2+ pool is first released by bright light in 0Ca2+–0Na+ solution and the cone returned to Ringer, the time course of Ca2+ decline is much faster than in Ringer without previous light exposure. This indicates that the time constants of 0.5 and 3.8 s actually reflect a sum of Na+/Ca2+-K+ exchange and light-induced release of Ca2+. The Ca2+ released by light appears to come from at least two sites, the first comprising 66% of the total pool and half-released by bleaching 4.8% of the pigment. Release of the remaining Ca2+ from the second site requires the bleaching of nearly all of the pigment. If, after release, the cone is maintained in darkness, a substantial fraction of the Ca2+ returns to the release pool even in the absence of pigment regeneration. The light-induced release of Ca2+ can produce a modulation of the dark current as large as 0.75 pA independently of the normal transduction cascade, though the rise time of the current is considerably slower than the normal light response. These experiments show that Ca2+ can be released within the cone outer segment by light intensities within the physiological range of photopic vision. The role this Ca2+ release plays remains unresolved.

Using a novel suite of computer-generated visual stimuli that mimicked components of optic flow, the visual responses of the tropical land crab, Cardisoma guanhumi, were investigated. We show that crabs are normally successful in distinguishing the rotational and translational components of the optic flow field, showing strong optokinetic responses to the former but not the latter. This ability was not dependant on the orientation of the crab, occurring both in “forwards-walking” and “sideways-walking” configurations. However, under conditions of low overall light intensity and/or low object/background contrast, the separation mechanism shows partial failure causing the crab to generate compensatory eye movements to translation, particularly in response to low-frequency (low-velocity) stimuli. Using this discovery, we then tested the ability of crabs to separate rotational and translational components in a combined rotation/translation flow field under different conditions. We demonstrate that, while crabs can successfully separate such a combined flow field under normal circumstances, showing compensatory eye movements only to the rotational component, they are unable to make this separation under conditions of low overall light intensity and low object/background contrast. Here, the responses to both flow-field components show summation when they are in phase, but, surprisingly, there is little reduction in the amplitude of responses to rotation when the translational component is in antiphase. Our results demonstrate that the crab's visual system finds separation of flow-field components a harder task than detection of movement, since the former shows partial failure at light intensities and/or object/background contrasts at which movement of the world around the crab is still generating high-gain optokinetic responses.

To investigate the effect of foveal inhomogeneities on sensitivity to chromatic stimuli, we measured simple reaction times (RTs) and detection thresholds to temporally and spatially blurred isoluminant stimuli at retinal eccentricities from 0 deg to 8 deg. Three color-normal subjects participated. Contrast gain was derived from the slope of the RT versus contrast function. With a Gaussian spatial distribution (S.D. = 0.5 deg) and modulation between white (CIE x,y,L = 0.31, 0.316, 12.5 cd.m−2) and blue (MBDKL 90 deg), gain was maximal at about 2-deg eccentricity and declined by approximately 1 log unit towards the center and the periphery. The red (0 deg) and green (180 deg) cardinal axes showed maximum gain in the center, whilst the yellow (270 deg) data were intermediate. Although the spatial extent of the Gaussian spot was much larger than the S-cone free zone, we wished to determine whether foveal tritanopia was responsible for the marked drop in sensitivity to the 90-deg stimulus. To align the color vector along a tritan line, we used a smaller disk (0.3 deg) with a blurred edge and measured detection threshold, rotating the vector until minimum central sensitivity was obtained. Other workers have used transient tritanopia or minimally distinct border to similar effect. By repeating this at different locations in color space, a group of vectors were obtained. These converged near to the S-cone co-punctal point, evidence that they lay along tritan confusion lines. These threshold findings were then confirmed using the RT-derived contrast gain function. The tritan vectors were less pronounced as stimulus size increased. With the vector optimized to produce foveal tritanopia, the RT gain versus eccentricity functions for the 90-deg and 270-deg stimuli both fell markedly in the center and periphery, and sensitivity peaked at about 3-deg eccentricity. There are some similarities between these findings and the underlying photoreceptor distributions. As a result, there is a greater difference in gain between red–green and blue–yellow systems in the center than in the near periphery. We conclude that the RT versus contrast function is a sensitive index of foveal opponency.

The starburst amacrine cell (SBAC), found in all mammalian retinas, is thought to provide the directional inhibitory input recorded in On–Off direction-selective ganglion cells (DSGCs). While voltage recordings from the somas of SBACs have not shown robust direction selectivity (DS), the dendritic tips of these cells display direction-selective calcium signals, even when γ-aminobutyric acid (GABAa,c) channels are blocked, implying that inhibition is not necessary to generate DS. This suggested that the distinctive morphology of the SBAC could generate a DS signal at the dendritic tips, where most of its synaptic output is located. To explore this possibility, we constructed a compartmental model incorporating realistic morphological structure, passive membrane properties, and excitatory inputs. We found robust DS at the dendritic tips but not at the soma. Two-spot apparent motion and annulus radial motion produced weak DS, but thin bars produced robust DS. For these stimuli, DS was caused by the interaction of a local synaptic input signal with a temporally delayed “global” signal, that is, an excitatory postsynaptic potential (EPSP) that spread from the activated inputs into the soma and throughout the dendritic tree. In the preferred direction the signals in the dendritic tips coincided, allowing summation, whereas in the null direction the local signal preceded the global signal, preventing summation. Sine-wave grating stimuli produced the greatest amount of DS, especially at high velocities and low spatial frequencies. The sine-wave DS responses could be accounted for by a simple mathematical model, which summed phase-shifted signals from soma and dendritic tip. By testing different artificial morphologies, we discovered DS was relatively independent of the morphological details, but depended on having a sufficient number of inputs at the distal tips and a limited electrotonic isolation. Adding voltage-gated calcium channels to the model showed that their threshold effect can amplify DS in the intracellular calcium signal.

Although a number of global mechanisms have been proposed over the years that explain how crabs might separate the rotational and translational components of their optic flow field, there has been no evidence to date that local mechanisms such as motion parallax are used in this separation. We describe here a study that takes advantage of a recently developed suite of computer-generated visual stimuli that creates a three-dimensional world surrounding the crab in which we can simulate translational and rotational optic flow. We show that, while motion parallax is not the only mechanism used in flow-field separation, it does play a role in the recognition of translational optic flow fields in that, under conditions of low overall light intensity and low contrast ratio when crabs find the distinction between rotation and translation harder, smaller eye movements occur in response to translation when motion parallax cues are present than when they are absent. Thus, motion parallax is one of many cues that crabs use to separate rotational and translational optic flow by showing compensatory eye movements to only the former.

Shapiro et al. (2004) introduced a new visual effect (the induced contrast asynchrony) that demonstrates a perceptual separation between the response to a modulated light and the response to contrast of the light relative to background. The effect is composed of two physically identical disks, one surrounded by a dark annulus and the other by a light annulus. The luminance levels of both central disks were modulated in time, producing a stimulus with in-phase luminance modulation and antiphase contrast modulation. Observers primarily perceived the disks to be modulating asynchronously (i.e. they perceived the contrast), but at low temporal frequencies could also track the luminance level. Here we document that the induced contrast asynchrony disappears when the surrounds are achromatic and the center lights are modulated near the equiluminant axis. Observers viewed 1-deg-diameter disks embedded 2-deg-diameter achromatic surrounds. The chromaticity of the disks was modulated in time (1 Hz) along lines in an S versus Luminance cardinal color plane and an L-M versus Luminance cardinal color plane; observers responded as to whether the modulation appeared in phase. For all observers and both color planes, the lights appeared in phase most frequently at angles near the standard observer's equiluminant line and out of phase at angles further away from that line. Observers differed in the range of angles that produce the appearance of in-phase modulation. The results suggest that induced contrast asynchronies may be useful as a technique for equating luminance of disparate lights.

The dorso-laterally located eyes of the southern hemisphere lamprey Mordacia mordax (Agnatha) contain a single morphological type of retinal photoreceptor, which possesses ultrastructural characteristics of both rods and cones. This photoreceptor has a large refractile ellipsosome in the inner segment and a long cylindrical outer segment surrounded by a retinal pigment epithelium that contains two types of tapetal reflectors. The photoreceptors form a hexagonal array and attain their peak density (33,200 receptors/mm2) in the ventro-temporal retina. Using the size and spacing of the photoreceptors and direct measures of aperture size and eye dimensions, the peak spatial resolving power and optical sensitivity are estimated to be 1.7 cycles deg−1 (minimum separable angle of 34′7′′) and 0.64 μm2 steradian (white light) and 1.38 μm2 steradian (preferred wavelength or λmax), respectively. Microspectrophotometry reveals that the visual pigment located within the outer segment is a rhodopsin with a wavelength of maximum absorbance (λmax) at 514 nm. The ellipsosome has very low absorptance (<0.05) across the measured spectrum (350–750 nm) and probably does not act as a spectral filter. In contrast to all other lampreys studied, the optimized receptor packing, the large width of the ellipsosome-bearing inner segment, together with the presence of a retinal tapetum in the photophobic Mordacia, all represent adaptations for low light vision and optimizing photon capture.

Light-evoked currents were recorded from rod bipolar cells in a dark-adapted mouse retinal slice preparation. Low-intensity light steps evoked a sustained inward current. Saturating light steps evoked an inward current with an initial peak that inactivated, with a time constant of about 60–70 ms, to a steady plateau level that was maintained for the duration of the step. The inactivation was strongest at hyperpolarized potentials, and absent at positive potentials. Inactivation was mediated by an increase in the intracellular calcium concentration, as it was abolished in cells dialyzed with 10 mM BAPTA, but was present in cells dialyzed with 1 mM EGTA. Moreover, responses to brief flashes of light were broader in the presence of intracellular BAPTA indicating that the calcium feedback actively shapes the time course of the light responses. Recovery from inactivation observed for paired-pulse stimuli occurred with a time constant of about 375 ms. Calcium feedback could act to increase the dynamic range of the bipolar cells, and to reduce variability in the amplitude and duration of the single-photon signal. This may be important for nonlinear processing at downstream sites of convergence from rod bipolar cells to AII amacrine cells. A model in which intracellular calcium rapidly binds to the light-gated channel and reduces the conductance can account for the results.

The aim of this study was to obtain information about single cone class driven activity in the inner and outer retina in humans. We examined outer retinal activity with the multifocal electroretinogram (mfERG) and inner retinal activity using multifocal oscillatory potentials (mfOPs). A standard (black-white) stimulus was used, as well as stimuli aimed at isolating a single photoreceptor class. The results of 10 trichromats were compared to those of 2 protanopes and 2 deuteranopes. At both retinal layers we find that trichromats show cone isolating response amplitudes that reflect the expected number of cones and that single- gene dichromats have a similar total number of functioning cones as trichromats. The ratio of the responses of the L- and M-cones is slightly smaller for the mfOPs than for the mfERGs. The results indicate that there are major changes in the gain of retinal signals after the inner plexiform layer.