Smaller model subunits of 20 μm diameter, CP-868596 in vivo which are still larger than typical salamander photoreceptors (Mariani, 1986 and Sherry et al., 1998), are not consistent with the experimental data (Figure 4C), indicating that the nonlinearities do not occur on the level of photoreceptor signals. Although static nonlinear signaling of bipolar cells may underlie the threshold-quadratic

nonlinearity, it cannot explain the striking difference between the shapes of iso-rate and iso-latency curves for homogeneity detectors. To build an intuition for the processes that give rise to this surprising discrepancy, we analyzed the temporal response profiles for different stimuli along the iso-response curves (Figure 5). To do so, we measured iso-response curves and then chose three characteristic points on the curves for repeated measurements of the corresponding stimuli in randomized

fashion. For cells with similar iso-rate and iso-latency curves, we found, as expected, that response patterns had virtually identical temporal structure along iso-rate curves (Figure 5A). For homogeneity detectors, we first consider stimuli that lie along an iso-latency curve (Figure 5B). As a stronger stimulus MK-2206 nmr typically leads to shorter latency (Figure 2D) (Sestokas et al., 1987), the iso-latency condition means that the different stimulus layouts initially were equally effective. Subsequently, however, the activity under stimulation of half the receptive field (Figure 5B, green and orange lines) did not rise as strongly and last as long as for homogeneous stimulation (Figure 5B, black line). Why did the activity not continue in the same way for the two layouts even though the latency suggested them to be equally strong? A plausible interpretation is that spike bursts for stimulation of half the receptive field were affected by a suppression mechanism Thymidine kinase that became effective shortly after the initial phase of the spike burst. This view is consistent with the spike patterns along the iso-rate curves (Figure 5C).

Here, the stimulation of half the receptive field has to occur at considerably higher contrast to enforce the same spike count. During the initial response part, this higher contrast provides a much more potent stimulus, thus leading to shorter response latencies (Sestokas et al., 1987). The response to homogeneous stimulation, on the other hand, starts later and reaches a smaller peak firing rate, corresponding to the much smaller applied contrast. But it compensates by the slightly longer response duration, presumably due to less suppression, to reach the same average spike count. We thus hypothesize that a suppression mechanism acts on homogeneity detectors for strong local stimulation. Note that local stimulation refers to activation of half the receptive field center in our standard stimulus layout, but strong stimulation in smaller regions also triggers the suppression (Figure 3F).