Abstract

BackgroundThe challenge of classifying cortical interneurons is yet to be solved. Data-driven classification into established morphological types may provide insight and practical value.ResultsWe trained models using 217 high-quality morphologies of rat somatosensory neocortex interneurons reconstructed by a single laboratory and pre-classified into eight types. We quantified 103 axonal and dendritic morphometrics, including novel ones that capture features such as arbor orientation, extent in layer one, and dendritic polarity. We trained a one-versus-rest classifier for each type, combining well-known supervised classification algorithms with feature selection and over- and under-sampling. We accurately classified the nest basket, Martinotti, and basket cell types with the Martinotti model outperforming 39 out of 42 leading neuroscientists. We had moderate accuracy for the double bouquet, small and large basket types, and limited accuracy for the chandelier and bitufted types. We characterized the types with interpretable models or with up to ten morphometrics.ConclusionExcept for large basket, 50 high-quality reconstructions sufficed to learn an accurate model of a type. Improving these models may require quantifying complex arborization patterns and finding correlates of bouton-related features. Our study brings attention to practical aspects important for neuron classification and is readily reproducible, with all code and data available online.

Highlights

  • The challenge of classifying cortical interneurons is yet to be solved

  • We describe the BA, Nest basket (NBC), Double bouquet (DBC), Small basket (SBC), and SBC types in terms of the morphometrics selected with random forest (RF) random forest balanced variable importance (BVI), and the MC type in terms of those selected with KW followed by classification and regression trees (CART) and Lasso regularized logistic regression (RMLR) embedded feature selection

  • We applied well-known classification algorithms and learned accurate (F-measure values above 0.80), competitive with neuroscientists, models for the BA, MC, and NBC types, and moderately accurate (F-measure above 0.70) models for the DBC and SBC types, we had less than 30 cells of the latter two types

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Summary

Methods

We provide an overview of the applied methodology Details, such as the definitions of morphometrics, are provided in Additional file 1. Data We used 228 hind-limb somatosensory cortex interneuron morphologies from two-week-old male Wistar (Han) rats. These cells were previously reconstructed by the Laboratory for Neural Microcircuitry and used by [13] for simulating a cortical microcircuit. These cells were previously reconstructed by the Laboratory for Neural Microcircuitry and used by [13] for simulating a cortical microcircuit8 They corrected shrinkage along the Z-axis, while shrinkage along the X and Y axes was of approximately 10%. Α = 0.05 adjust = FDR bvi > 0.01. Learner parameters are the RF parameters used internally for RF BVI count

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