Current source density analysis of linear and non-linear components of the primate electroretinogram.

1. We have used the method of current source density analysis to locate the generators of harmonic electroretinogram (ERG) responses to contrast-modulated pattern and uniform-field stimuli in the primate retina. 2. Sinusoidal steady-state analysis was used, with a stimulus temporal frequency of 8 Hz. Fundamental and second-harmonic response components were measured for the uniform-field response. The second harmonic of the average of contrast-reversal pattern responses obtained at a series of spatial phases was also determined in the same experiments. In addition, retinal tissue resistance was measured. All of these measurements were obtained at a series of equally spaced depths in the retina. 3. Retinal resistivity was not observed to vary systematically with depth. In addition, any plausible undetected inhomogeneities of resistivity with depth were found to slightly affect the relative magnitudes of estimated current sources and sinks, but to have little effect on their localization. 4. In a given penetration, the phase lag of each harmonic component was relatively constant with depth in most cases; however the magnitude of this phase lag sometimes varied in different penetrations. To compare data from different penetrations, the constant phase lag for each harmonic was estimated, and the response data phase-shifted so as to bring all data into a standard (cosine) phase. 5. The resulting current source density analyses were found to be quite consistent in overall form for different penetrations and in different animals. These data were averaged to obtain a final estimate of the depth profiles for generators of different ERG components. 6. The uniform-field fundamental response was found to have a predominant source-sink pair in the distal half of the retina (receptor layer to outer plexiform layer). The pattern (second-harmonic) response generators had a quite different depth profile, consisting mainly of a source-sink pair in the proximal 20% of the retina (encompassing the nerve fibre layer to the middle of the inner plexiform layer). The uniform-field second-harmonic response showed a current source density (CSD) depth profile with multiple sources/sinks, as if it contained contributions from the other two.