Thus, new methods are needed to assess what kinds of nonlinear operations are at work. One approach has been to

use parameterized models of ganglion cell stimulus–response functions and find the nonlinear transformation from the set of parameters that maximizes how the model output fits to measured responses (Victor and Shapley, 1979, Victor, 1988, Baccus et al., 2008 and Gollisch DAPT order and Meister, 2008a). This approach works well when a good understanding of the basic model structure already exists and when sufficient data can be obtained to extract the potentially large number of parameters in the model. Yet, this approach can naturally only capture such nonlinear operations within the scope of the parameterization, and complex

models with many parameters may be difficult to handle computationally and prohibit reliable extraction of the optimal parameter sets. Thus, limitations in data availability and computational CB-839 clinical trial tools may restrict the nonlinear transformations to those that can be described with only one or few parameters, such as a threshold and an exponent. As discussed above, iso-response measurements represent an alternative, as they provide a way to assess nonlinear stimulus integration without the need of an a priori parameterization of the nonlinearities ( Bölinger and Gollisch, 2012). The strength of the method lies in the fact that the measured iso-response curves provide a characteristic signature of the type of stimulus integration and that this signature is independent of nonlinear transformations at the output stage of the system. Note, though, that the functional forms of the nonlinear transformations are not provided directly, but are inferred from analyzing the shape of the iso-response curves, for example by comparing or fitting to computational model predictions. Furthermore, in order to apply the technique efficiently, automated online analysis

and closed-loop experimental designs have to be set up, which may make the method more demanding than, for example, reverse correlation analyses with white-noise stimulation. Based on the iso-response method, it has been possible to distinguish between two Methisazone fundamentally different types of nonlinear spatial integration (Bölinger and Gollisch, 2012), thus showing that the complexity of nonlinear transformations within the receptive field goes beyond the often assumed threshold-linear half-wave rectification. These Libraries findings furthermore suggest that not all nonlinearly integrating ganglion cells should be classified under the single label of Y cells; instead, there may be important functional divisions between nonlinear ganglion cells, potentially corresponding to different types of ganglion cells as determined by anatomy or molecular markers.