Contribution of cone photoreceptors and post-receptoral mechanisms to the human photopic electroretinogram

We recorded the electroretinogram (ERG) from human subjects with normal vision, using ganzfeld stimulation in the presence of rod-suppressing blue background light. In families of responses to flashes of increasing intensity, we investigated features of both receptoral and post-receptoral origin. Firstly, we found that the oscillatorypotentials (OPs, that have long been known to be post-receptoral) exhibited a time course that was invariant over a range of bright flash intensities. Secondly, we found that the photopic b-wave (which probably originates in cone ON bipolar cells) was most pronounced after test flashes of around 20 Td s, and could be suppressed either by increasing the test flash intensity or by applying a second flash after the test flash. We obtained estimates of the time course of the cone photoreceptor response using the paired-flash technique, in which an intense 'probe' flash was delivered at different times after a test flash. The response to the probe flash was recorded and, its amplitude was measured at early times after the probe flash. Estimates obtained in this way were of normalized amplitude, but could be scaled to an absolute amplitude by making an assumption about the level of probe-flash response that corresponded to complete suppression of photoreceptor current. For moderately bright test flashes the estimated cone photoreceptor response at early times coincided closely with the a-wave of the test flash ERG. However, the maximal size of this estimated response accounted for only about 70% of the peak a-wave amplitude in the case of bright flashes, and for an even smaller proportion after flashes of lower intensity, and we take this to indicate the existence of a third substantial post-receptoral contribution to the a-wave. For dim flashes, the time-to-peak of the cone response was around 15-20 ms, and for saturating flashes the dominant time constant of recovery was about 18 ms. The intensity dependence of the estimated cone response amplitude at fixed times followed an exponential saturation relation. We provide a comparison between our estimates of photoreceptor responses from human cones, and recent estimates from monkey cones obtained using related ERG approaches, and earlier single-cell measurements from isolated primate cones.