Activation of metabotropic glutamate receptors modulates the voltage-gated sustained calcium current in a teleost horizontal cell.
(1/1671)
In the teleost retina, cone horizontal cells contain a voltage-activated sustained calcium current, which has been proposed to be involved in visual processing. Recently, several studies have demonstrated that modulation of voltage-gated channels can occur through activation of metabotropic glutamate receptors (mGluRs). Because glutamate is the excitatory neurotransmitter in the vertebrate retina, we have used whole cell electrophysiological techniques to examine the effect of mGluR activation on the sustained voltage-gated calcium current found in isolated cone horizontal cells in the catfish retina. In pharmacological conditions that blocked voltage-gated sodium and potassium channels, as well as N-methyl-D-aspartate (NMDA) and non-NMDA channels, application of L-glutamate or 1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) to voltage-clamped cone horizontal cells acted to increase the amplitude of the calcium current, expand the activation range of the calcium current by 10 mV into the cell's physiological operating range, and shift the peak calcium current by -5 mV. To identify and characterize the mGluR subtypes found on catfish cone horizontal cells, agonists of group I, group II, or group III mGluRs were applied via perfusion. Group I and group III mGluR agonists mimicked the effect of L-glutamate or 1S,3R-ACPD, whereas group II mGluR agonists had no effect on L-type calcium current activity. Inhibition studies demonstrated that group I mGluR antagonists significantly blocked the modulatory effect of the group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine. Similar results were obtained when the group III mGluR agonist, L-2-amino-4-phosphonobutyric acid, was applied in the presence of a group III mGluR antagonist. These results provide evidence for two groups of mGluR subtypes on catfish cone horizontal cells. Activation of these mGluRs is linked to modulation of the voltage-gated sustained calcium current. (+info)
Formate-induced inhibition of photoreceptor function in methanol intoxication.
(2/1671)
Formic acid is the toxic metabolite responsible for the retinal and optic nerve toxicity produced in methanol intoxication. Previous studies in our laboratory have documented formate-induced retinal dysfunction and histopathology in a rodent model of methanol intoxication. The present studies define the time and concentration dependence of formate-induced retinal toxicity in methanol-intoxicated rats. Retinal function was assessed 24, 48, and 72 h after the initial dose of methanol by flicker electroretinographic measurements. Retinal histopathology was assessed at the same time intervals. Rod- and cone-mediated electroretinogram (ERG) responses were attenuated in a formate concentration- and time-dependent manner, and both retinal sensitivity and maximal responsiveness to light were diminished. Attenuation of UV-cone-mediated responses was temporally delayed in comparison to the functional deficits observed in the 15 Hz/510 nm responses, which have a rod-mediated component and occurred at significantly higher formate concentrations. Both 15 Hz/510 nm and UV-cone-mediated ERG responses were undetectable by 72 h; however, if light intensity was increased, a retinal ERG response could be recorded, indicating that photoreceptor function was profoundly attenuated, but not abolished, under these intoxication conditions. Functional changes preceded structural alterations. Histopathological changes were most pronounced in the outer retina with evidence of inner segment swelling, photoreceptor mitochondrial disruption, and the appearance of fragmented photoreceptor nuclei in the outer nuclear layer. The nature of both the functional and structural alterations observed are consistent with formate-induced inhibition of mitochondrial energy production, resulting in photoreceptor dysfunction and pathology. (+info)
Cone signal contributions to electroretinograms [correction of electrograms] in dichromats and trichromats.
(3/1671)
PURPOSE: To find out how the different cone types contribute to the electroretinogram (ERG) by quantifying the contribution of the signal pathways originating in the long (L-) and the middle (M-) wavelength-sensitive cones to the total ERG response amplitude and phase. METHODS: ERG response amplitudes and phases were measured to cone-isolating stimuli and to different combinations of L- and M-cone modulation. Conditions were chosen to exclude any contribution of the short wavelength-sensitive (S-) cones. The sensitivity of the ERG to the L and the M cones was defined as the cone contrast gain. RESULTS: In the present paper, a model is provided that describes the ERG contrast gains and ERG thresholds in dichromats and color normal trichromats. For the X-chromosome-linked dichromats, the contrast gains of only one cone type (either the L or the M cones) sufficed to describe the ERG thresholds for all stimulus conditions. Data suggest that the M-cone contrast gains of protanopes are larger than the L-cone contrast gains of deuteranopes. The response thresholds of the trichromats are modeled by assuming a vector summation of signals originating in the L and the M cones. Their L- and M-cone contrast gains are close to a linear interpolation of the data obtained from the dichromats. Nearly all trichromats had larger L- than M-cone contrast gains. Data from a large population of trichromats were examined to study the individual variations in cone weightings and in the phases of the cone pathway responses. CONCLUSIONS: The data strongly suggest that the missing cone type in dichromats is replaced by the remaining cone type. The mean L-cone to M-cone weighting ratio in trichromats was found to be approximately 4:1. But there is a substantial interindividual variability between trichromats. The response phases of the L- and the M-cone pathways can be reliably quantified using the response phases to the cone-isolating stimuli or using a vector addition of L- and M-cone signals. (+info)
Human cone pigment expressed in transgenic mice yields altered vision.
(4/1671)
Genetically driven alterations in the complement of retinal photopigments are fundamental steps in the evolution of vision. We sought to determine how a newly added photopigment might impact vision by studying a transgenic mouse that expresses a human cone photopigment. Electroretinogram (ERG) measurements indicate that the added pigment works well, significantly changing spectral sensitivity without deleteriously affecting the operation of the native cone pigments. Visual capacities of the transgenic mice were established in behavioral tests. The new pigment was found to provide a significant expansion of the spectral range over which mice can perceive light, thus underlining the immediate utility of acquiring a new photopigment. The transgenic mouse also has the receptor basis for a novel color vision capacity, but tests show that potential was not realized. This failure likely reflects limitations in the organizational arrangement of the mouse retina. (+info)
Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors.
(5/1671)
Circadian rhythms of mammals are entrained by light to follow the daily solar cycle (photoentrainment). To determine whether retinal rods and cones are required for this response, the effects of light on the regulation of circadian wheel-running behavior were examined in mice lacking these photoreceptors. Mice without cones (cl) or without both rods and cones (rdta/cl) showed unattenuated phase-shifting responses to light. Removal of the eyes abolishes this behavior. Thus, neither rods nor cones are required for photoentrainment, and the murine eye contains additional photoreceptors that regulate the circadian clock. (+info)
Optical, receptoral, and retinal constraints on foveal and peripheral vision in the human neonate.
(6/1671)
We examined the properties of the foveal, parafoveal, and near peripheral cone lattice in human neonates. To estimate the ability of these lattices to transmit the information used in contrast sensitivity and visual acuity tasks, we constructed ideal-observer models with the optics and photoreceptors of the neonatal eye at retinal eccentricities of 0, 5, and 10 degrees. For ideal-observer models limited by photon noise, the eye's optics, and cone properties, contrast sensitivity was higher in the parafovea and near periphery than in the fovea. However, receptor pooling probably occurs in the neonate's parafovea and near periphery as it does in mature eyes. When we add a receptor-pooling stage to the models of the parafovea and near periphery, ideal acuity is similar in the fovea, parafovea, and near periphery. Comparisons of ideal and real sensitivity indicate that optical and receptoral immaturities impose a significant constraint on neonatal contrast sensitivity and acuity, but that immaturities in later processing stages must also limit visual performance. (+info)
Chromatic masking in the (delta L/L, delta M/M) plane of cone-contrast space reveals only two detection mechanisms.
(7/1671)
The post-receptoral mechanisms that mediate detection of stimuli in the (delta L/L, delta M/M) plane of color space were characterized using noise masking. Chromatic masking noises of different chromaticities and spatial configurations were used, and threshold contours for the detection of Gaussian and Gabor tests were measured. The results do not show masking that is narrowly-selective for the chromaticity of the noise. On the contrary, our findings suggest that detection of these tests is mediated only by an opponent chromatic mechanism (a red-green mechanism) and a non-opponent luminance mechanism. These results are not consistent with the hypothesis of multiple chromatic mechanisms mediating detection in this color plane [1]. (+info)
S-cone signals to temporal OFF-channels: asymmetrical connections to postreceptoral chromatic mechanisms.
(8/1671)
Psychophysical tests of S-cone contributions to temporal ON- and OFF-channels were conducted. Detection thresholds for S-cone modulation were measured with two kinds of test stimuli presented on a CRT: a rapid-on sawtooth test and a rapid-off sawtooth test, assumed to be detected differentially by temporal ON- and OFF-channels, respectively. S-cone related ON- and OFF-temporal responses were separated by adapting for 5 min to 1 Hz monochromatic (420, 440, 450, 540, or 650 nm in separate sessions) sawtooth flicker presented in Maxwellian view. Circular test stimuli, with a sawtooth temporal profile and a Gaussian spatial taper, were presented for 1 s in one of four quadrants 1.0 degree from a central fixation point. A four-alternative forced-choice method combined with a double-staircase procedure was used to determine ON- and OFF-thresholds in the same session. Following adaptation, the threshold elevation was greater if the polarity of the test stimulus was the same as the polarity of the sawtooth adaptation flicker, consistent with separate ON- and OFF-responses from S-cones. This asymmetrical pattern was obtained, however, only when the adaptation stimuli appeared blue with a little redness. When the adaptation flicker had a clear reddish hue component, the threshold elevation did not depend on the polarity of the sawtooth test stimuli. These results are consistent with a model in which OFF-signals originating from S cones are maintained by a postreceptoral mechanism signaling redness, but not by a postreceptoral chromatic mechanism signaling blueness. (+info)