Abstract

Retinal ganglion cells, the sole output neurons of the retina, exhibit surprising diversity. A recent study reported over 30 distinct types in the mouse retina, indicating that the processing of visual information is highly parallelised in the brain. The advent of high density multi-electrode arrays now enables recording from many hundreds to thousands of neurons from a single retina. Here we describe a method for the automatic classification of large-scale retinal recordings using a simple stimulus paradigm and a spike train distance measure as a clustering metric. We evaluate our approach using synthetic spike trains, and demonstrate that major known cell types are identified in high-density recording sessions from the mouse retina with around 1,000 retinal ganglion cells. A comparison across different retinas reveals substantial variability between preparations, suggesting pooling data across retinas should be approached with caution. As a parameter-free method, our approach is broadly applicable for cellular physiological classification in all sensory modalities.

Highlights

  • It is well established that the retina has multiple, functionally complementary populations of retinal ganglion cells (RGCs), which together transmit visual information to various central visual areas (Roska and Werblin, 2001)

  • Extending an idea first presented by Zeck and Masland (2007), here we present a method for clustering RGCs based on spike distance measures, which is suited for high density recordings

  • This requires a distance measure with the metric properties of non-negativity, zero distance for identity, symmetry and subadditivity. These conditions are fulfilled by a number of metrics (Victor, 2005; Kreuz et al, 2007, 2013), of which we evaluated the nonparametric inter-spike intervals (ISI) and SPIKE distance measures

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Summary

Introduction

It is well established that the retina has multiple, functionally complementary populations of retinal ganglion cells (RGCs), which together transmit visual information to various central visual areas (Roska and Werblin, 2001). The actual classification of RGCs typically requires a combination of measures of their cellular physiology, light responses, morphology and, more recently, their gene expression patterns and connectome (Helmstaedter et al, 2013; Macosko et al, 2015; Sanes and Masland, 2015; Krieger et al, 2017; Rheaume et al, 2018). Despite such well defined principles, in practice classification of RGC types has been challenging because it is difficult to implement all criteria in a single experiment. Features were extracted from responses to a set of stimuli designed to reveal the main spatial and temporal

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