Dissecting cellular diversity of cortical GABAergic cells across multiple modalities: A turning point in neuronal taxonomy

Abstract

Decoding the complexity of the brain requires an understanding of the architecture, function, and development of its neuronal circuits. Neuronal classifications that group neurons based on specific features/behaviors have become essential to further analyze the different subtypes in a systematic and reproducible way. A comprehensive taxonomic framework, accounting for multiple defining and quantitative features, will provide the reference to infer generalized rules for cells ascribed to the same neuronal type, and eventually predict cellular behaviors, even in the absence of experimental measures. Technologies that enable cell-type classification in the nervous system are rapidly evolving in scalability and resolution. While these approaches depict astonishing diversity in neuronal morphology, electrophysiology, and gene expression, a robust metric of the coherence between different profiling modalities leading to a unified classification is still largely missing. Focusing on GABAergic neurons of the cerebral cortex, Gouwens et al.¹ pioneered the first integrated cell-type classification based on the simultaneous analysis of the transcriptional networks, the recording of intrinsic electrophysiological properties, and the reconstruction of 3D morphologies of the same cell. Their comprehensive and high-quality data provide a new framework to shed light on what may be considered a "neuronal cell type."

Keywords: GABAergic cells; cellular diversity; classification; neuronal taxonomy.

Figure 1. Illustration by Santiago Ramon y Cajal depicting short axon neurons

This image, originally published in 1899 (reproduced under public domain – for the English translation see 2), nicely conveys the complexity/diversity of cortical interneurons, mainly depicted by their distinct morphology and the wide range of radial and tangential expansion of their axons. It clearly shows a Martinotti cell (G) as it could be described today. English translation of figure legend: "Cells with short axons of the plexiform and small- and medium-sized pyramidal cell layers from motor cortex of infant aged one month and few days. A, B, C, horizontal cells of the plexiform layer; D, cell with horizontal axon; E, large cell with very short diffusely subdivided axons; F, G, spider-shaped cells whose axons form dense plexus (G) up to plexiform layer; and H, J, bipanicled cells.".