The impact of a disease on phototransduction can be assessed by fitting the leading edge of the rod a-wave to high-energy flashes with a quantitative expression. Two parameters of rod receptor activity are obtained, S (sensitivity) and Rm (maximum response). In this study, the meaning of these parameters and examples of conditions that change them were examined. In addition, a new protocol was developed for obtaining these parameters. A set of three to five white flashes were first presented in the dark and then on an adapting field (30 cd/m2). Subtracting the light-adapted responses from the dark-adapted responses yielded isolated rod a-wave responses. A clinical protocol was developed based on a single white flash energy. It is possible to determine whether a disease is producing a change in S and/or Rm with this single flash energy without the use of any equations.

Electroretinography↗

PubMedDate not supplied

Human cone receptor activity: the leading edge of the a-wave and models of receptor activity.

The leading edge of the a-wave of the electroretinogram (ERG) was evaluated as a measure of human cone photoreceptor activity. The amplitude of the cone a-wave elicited by flashes of different energy was compared to the predictions of a class of models from in vitro studies of cone photoreceptors. These models successfully describe the leading edge of the a-wave. Thus, the human cone a-wave can be used to test hypotheses about normal and abnormal cone receptors. The ability of the human cone to adjust its sensitivity in the presence of steady adapting lights was assessed by recording cone a-waves to flashes on adapting fields up to 3.9 log td in intensity and by comparing these responses to quantitative models of adaptation. The first 10 ms of the cone's response is little affected by field intensities up to 2.9 log td. The 3.9 log td field reduced the response to weak flashes by about a factor of 2.5 (0.4 log unit). This relatively small reduction in sensitivity can be attributed to a combination of response compression, pigment bleaching, and an adaptation mechanism that changes the gain without changing the time course. We conclude that either the human cones show relatively little adaptation or that they have an adaptation mechanism that involves a time-course change. That is, as we are limited with the a-wave to the first 10 ms or so of the cone's response, we cannot rule out a gain mechanism linked to a time-course change.

Adaptation, Ocular↗

PubMedDate not supplied

Photoresponses of human rods in vivo derived from paired-flash electroretinograms.

In the human eye, domination of the electroretinogram (ERG) by the b-wave and other postreceptor components ordinarily obscures all but the first few milliseconds of the rod photoreceptor response to a stimulating flash. However, recovery of the rod response after a bright rest flash can be analyzed using a paired-flash paradigm in which the test flash, presented at time zero, is followed at time t by a bright probe flash that rapidly saturates the rods (Birch et al., 1995). In ERG experiments on normal subjects, the hypothesis that a similar method can be used to obtain the full time course of the rod response to test flashes of subsaturating intensity was tested. Rod-only responses to probe flashes presented at varying times t after the test flash were used to derive a family of amplitudes A(t) that represented the putative rod response to the test flash. These rod-only responses to the probe flash were obtained by computational subtraction of the cone-mediated component of each probe flash response. With relatively weak test flashes (11-15 scot-td-s), the time course of the rod response to the test flash derived in this manner was consistent with a four-stage impulse response function of time-to-peak approximately 170 ms. A(170), the amplitude of the derived response at 170 ms, increased with test flash intensity (Itest) to a maximum value Amv and exhibited a dependence on Itest given approximately by the relation, A(170)/Amo = 1 - exp(-kItest), where k = 0.092 (scot-td-s)-1. In steady background light, the falling (i.e. recovery) phase of the derived response began earlier, and the sensitivity parameter k was reduced several-fold from its dark-adapted value. As the sensitivity, sensitivity, kinetics, and light-adaptation properties of the derived response correspond closely with those of photocurrent flash responses previously obtained from isolated rods in vitro, it was concluded that the response derived here from the human ERG approximates the course of the massed in vivo rod response to a test flash.

Adaptation, Ocular↗

PubMedDate not supplied

A comparison of the components of the multifocal and full-field ERGs.

The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs. The purpose here was to compare the components of this multifocal ERG to the components of the standard, full-field ERG. To record multifocal ERGs, an array of 103 hexagons was displayed on a monitor. Full-field (Ganzfeld) ERGs were elicited by flashes presented upon steady background fields. The latencies of two prominent subcomponents of the full-field ERG were altered by varying the intensity of the incremental flash or the intensity of the background field. By showing that similar manipulations of the multi-input parameters produce similar changes in latency, we were able to relate the components of the multifocal ERG to the components of the full-field ERG. The biphasic responses of the multifocal ERG appear to be generated by the same cells generating the a-wave and positive peaks of the full-field cone ERG.

Adult↗

PubMedDate not supplied

Threshold fluctuations on temporally modulated backgrounds: a possible physiological explanation based upon a recent computational model.

When a temporally fluctuating background is rapidly modulated (e.g. 30 Hz), the threshold variation of a superimposed flash (the probe) is approximately sinusoidal and in phase with the stimulus. But, with low rates of sinusoidal modulation (e.g. 1 Hz), the threshold variation is distinctly nonsinusoidal in shape. The bases of these aspects of the data, as well as an unmodulated, dc, threshold elevation, are poorly understood. Here 30-Hz and 1-Hz conditions are simulated using a new model of light adaptation (Wilson, 1997). By assuming that the OFF pathway is twice as sensitive as the ON pathway, the model correctly captured the key aspects of both conditions. The results suggest that the 1-Hz data are mediated by a mixture of ON and OFF pathways while the 30-Hz data are largely mediated by the OFF pathway. The probe thresholds on the 30-Hz background appear approximately sinusoidal and approximately in phase with the background stimulus. A number of factors contribute to this deceptively simple observation.

Adaptation, Ocular↗

PubMedDate not supplied

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.

Action Potentials↗