Multimodal cortical neuronal cell type classification

Pflugers Arch. 2024 May;476(5):721-733. doi: 10.1007/s00424-024-02923-2. Epub 2024 Feb 20.

Abstract

Since more than a century, neuroscientists have distinguished excitatory (glutamatergic) neurons with long-distance projections from inhibitory (GABAergic) neurons with local projections and established layer-dependent schemes for the ~ 80% excitatory (principal) cells as well as the ~ 20% inhibitory neurons. Whereas, in the early days, mainly morphological criteria were used to define cell types, later supplemented by electrophysiological and neurochemical properties, nowadays. single-cell transcriptomics is the method of choice for cell type classification. Bringing recent insight together, we conclude that despite all established layer- and area-dependent differences, there is a set of reliably identifiable cortical cell types that were named (among others) intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) for the excitatory cells, which altogether comprise ~ 56 transcriptomic cell types (t-types). By the same means, inhibitory neurons were subdivided into parvalbumin (PV), somatostatin (SST), vasoactive intestinal polypeptide (VIP), and "other (i.e. Lamp5/Sncg)" subpopulations, which altogether comprise ~ 60 t-types. The coming years will show which t-types actually translate into "real" cell types that show a common set of multimodal features, including not only transcriptome but also physiology and morphology as well as connectivity and ultimately function. Only with the better knowledge of clear-cut cell types and experimental access to them, we will be able to reveal their specific functions, a task which turned out to be difficult in a part of the brain being so much specialized for cognition as the cerebral cortex.

Keywords: Cerebral cortex; Excitatory neurons; Inhibitory neurons; Multimodal classification; Neuronal cell types; Transcriptomics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex* / cytology
  • Cerebral Cortex* / metabolism
  • Cerebral Cortex* / physiology
  • Humans
  • Neurons* / classification
  • Neurons* / metabolism
  • Neurons* / physiology
  • Transcriptome