Dataset Information

Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina.

ABSTRACT: Light adaptation changes both the sensitivity and maximum amplitude (Rmax) of the mouse photopic electroretinogram (ERG) b-wave. Using the ERG, we examined how modulation of gap junctional coupling between rod and cones alters the light-adapted ERG. To measure changes, a b-wave light adaptation enhancement factor (LAEF), was defined as the ratio of Rmax after 15 min light adaptation to Rmax recorded at the onset of an adapting light. For wild-type mice (WT), the LAEF averaged 2.64 ± 0.29, however, it was significantly reduced (1.06 ± 0.04) for connexin 36 knock out (Cx36KO) mice, which lack electrical coupling between photoreceptors. Wild type mice intraocularly injected with meclofenamic acid (MFA), a gap junction blocker, also showed a significantly reduced LAEF. Degeneration of rod photoreceptors significantly alters the effects of light adaptation on the photopic ERG response. Rd10 mice at P21, with large portions of their rod photoreceptors present in the retina, exhibited a similar b-wave enhancement as wildtype controls, with a LAEF of 2.55 ± 0.19. However, by P31 with most of their rod photoreceptors degenerated, rd10 mice had a much reduced b-wave enhancement during light-adaptation (LAEF of 1.54 ± 0.12). Flicker ERG responses showed a higher temporal amplitude in mesopic conditions for WT than those of Cx36KO mice, suggesting rod-cone coupling help high-frequency signals to pass from rods to cone pathways in the retina. In conclusion, our study provides a novel method to noninvasively measure the dynamics and modulation by the light adaptation for rod-cone gap junctional coupling in intact eyes.

SUBMITTER: Li Y

PROVIDER: S-EPMC7546330 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina.

Li Yichao Y Cohen Ethan D ED Qian Haohua H

Frontiers in cellular neuroscience 20200925

Light adaptation changes both the sensitivity and maximum amplitude (Rmax) of the mouse photopic electroretinogram (ERG) b-wave. Using the ERG, we examined how modulation of gap junctional coupling between rod and cones alters the light-adapted ERG. To measure changes, a b-wave light adaptation enhancement factor (LAEF), was defined as the ratio of Rmax after 15 min light adaptation to Rmax recorded at the onset of an adapting light. For wild-type mice (WT), the ...[more]

PMID: 33100974

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Project description:Key pointsMost vertebrate eyes have rods for dim-light vision and cones for brighter light and higher temporal sensitivity. Rods evolved from cone-like precursors through expression of different transduction genes or the same genes at different expression levels, but we do not know which molecular differences were most important. We approached this problem by analysing rod and cone responses with the same model but with different values for model parameters. We showed that, in addition to outer-segment volume, the most important differences between rods and cones are: (1) decreased transduction gain, reflecting smaller amplification in the G-protein cascade; (2) a faster rate of turnover of the second messenger cGMP in darkness; and (3) an accelerated rate of decay of the effector enzyme phosphodiesterase and perhaps also of activated visual pigment. We believe our analysis has identified the principal alterations during evolution responsible for the duplex retina.AbstractMost vertebrates have rod and cone photoreceptors, which differ in their sensitivity and response kinetics. We know that rods evolved from cone-like precursors through the expression of different transduction genes or the same genes at different levels, but we do not know which molecular differences were most important. We have approached this problem in mouse retina by analysing the kinetic differences between rod flash responses and recent voltage-clamp recordings of cone flash responses, using a model incorporating the principal features of photoreceptor transduction. We apply a novel method of analysis using the log-transform of the current, and we ask which of the model's dynamic parameters need be changed to transform the flash response of a rod into that of a cone. The most important changes are a decrease in the gain of the response, reflecting a reduction in amplification of the transduction cascade; an increase in the rate of turnover of cGMP in darkness; and an increase in the rate of decay of activated phosphodiesterase, with perhaps also an increase in the rate of decay of light-activated visual pigment. Although we cannot exclude other differences, and in particular alterations in the Ca2+ economy of the photoreceptors, we believe that we have identified the kinetic parameters principally responsible for the differences in the flash responses of the two kinds of photoreceptors, which were likely during evolution to have resulted in the duplex retina.

Project description:Key pointsMost vertebrate eyes have rod and cone photoreceptors, which use a signal transduction pathway consisting of many biological processes to transform light into an electrical response. We dissect and quantify the contribution of each of these processes to the photoreceptor light response by using a novel method of analysis that provides an analytical solution for the entire time course of the dim-flash light response. We find that the shape of the light response is exclusively controlled by deactivation parameters. Activation parameters scale this shape and alter the response amplitude. We show that the rising phase of the response depends on Ca2+ feedback, and we identify the deactivation parameters that control the recovery phase of the response. We devise new methods to extract values for deactivation and activation parameters from a separate analysis of response shape and response amplitude.AbstractVertebrate eyes have rod and cone photoreceptors, which use a complex transduction pathway comprising many biological processes to transform the absorption of light into an electrical response. A fundamental question in sensory transduction is how these processes contribute to the response. To study this question, we use a well-accepted phototransduction model, which we analyse with a novel method based on the log transform of the current. We derive an analytical solution that describes the entire time course of the photoreceptor response to dim flashes of light. We use this solution to dissect and quantify the contribution of each process to the response. We find that the entire dim-flash response is proportional to the flash intensity. By normalizing responses to unit amplitude, we define a waveform that is independent of the light intensity and characterizes the invariant shape of dim-flash responses. We show that this waveform is exclusively determined by deactivation rates; activation rates only scale the waveform and affect the amplitude. This analysis corrects a previous assumption that the rising phase is determined entirely by activation rates. We further show that the rising phase depends on Ca2+ feedback to the cyclase, contrary to current belief. We identify the deactivation rates that control the recovery phase of the response, and we devise new methods to extract activation and deactivation rates from an analysis of response shape and response amplitude. In summary, we provide a comprehensive understanding of how the various transduction processes produce the cellular response.

Dataset Information

Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina.

Publications

Rod and Cone Coupling Modulates Photopic ERG Responses in the Mouse Retina.

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