Classification of retinal ganglion cells: a statistical approach

Numerous studies have shown that retinal ganglion cells exhibit an array of responses to visual stimuli. This has led to the idea that these cells can be sorted into distinct physiological classes, such as linear versus nonlinear or on versus off. Although many classification schemes are widely accepted, few studies have provided statistical support to favor one scheme over another. Here we test whether some of the most widely used classification schemes can be statistically verified, using the mouse retina as the model system. We used a cluster analysis approach and focused on 4 standard response parameters: 1) response latency, 2) response duration, 3) relative amplitude of the on and off responses, and 4) degree of nonlinearity in the stimulus-to-response transformation. For each parameter, we plotted its distribution and tested quantitatively, using a bootstrap method, whether it divided into distinct clusters. Our analysis showed that mouse ganglion cells clustered into several groups based on response latency, duration, and relative amplitude of the on and off responses, but did not cluster into more than one group based on degree of nonlinearity-the latter formed a single, large, continuous group. Thus while some well-known schemes for classifying ganglion cells could be statistically verified, others could not. Knowledge of which schemes can be confirmed is important for building models of how retinal output is processed and how retinal circuits are built. Finally, this cluster analysis approach is general and can be used to test other classification proposals as well, both physiological and anatomical.