Indeed, simulating

this model circuit reproduces the characteristics of the iso-latency curve as well as of the iso-rate curves with and without inhibition block (Figure 7D). The simulation also shows that the nonconvex shape of the iso-rate curves becomes more pronounced for larger target spike counts (Figure 7E), similar to experimental observations (Figure 3E). This follows because the higher required visual contrast for reaching a higher spike count activates disproportionally more inhibition and thus leads to a stronger gain control effect. Individual neurons typically integrate multiple input components. How they perform this integration is a major factor in determining their computational function. Here, we C59 wnt solubility dmso have suggested to study neuronal integration by measuring iso-response stimuli (Figure 1) and applied this concept to the question how retinal ganglion cells integrate visual stimuli over their receptive field centers. The dominant RO4929097 nonlinearity that was extracted from these measurements was a threshold-quadratic transformation, which was apparent in all measured iso-latency

curves and many iso-rate curves (Figure 3). This nonlinearity occurred on a spatial scale that is consistent with bipolar cell receptive fields (Figure 4). Furthermore, a specific subclass of cells displayed iso-rate curves that fundamentally differed in shape from the iso-latency curves and were characterized by a particular sensitivity of the spike count for homogeneous stimulation DNA ligase (Figure 3C). For these homogeneity detectors, the difference between iso-latency and iso-rate curves appeared to result from a partial suppression of activity when strong local stimulation in a subregion of the receptive field was involved (Figure 5). This pointed toward a dynamic local gain control mechanism, which

was found to be mediated by a local inhibitory circuit (Figure 7), whereas a scenario based on synaptic depression was not consistent with data (Figure 6). The critical role of inhibition for homogeneity detectors further supports the hypothesis of a suppressive mechanism that acts on the spike burst for strong local stimulation. Alternative schemes in which responses might be actively boosted under homogeneous stimulation seem less congruent with a mechanism based on inhibition. The measurements of iso-response stimuli proved very suited to identify the details of these nonlinearities in ganglion cell receptive fields. First, it required only measurements of spike times from the ganglion cells. These can be obtained in long and stable extracellular recordings, which allowed for detailed characterizations. Second, these measurements could be performed quite efficiently by using automated online analysis and closed-loop control of the stimulation.