Perisomatic ultrastructure efficiently classifies cells in mouse cortex.

TitlePerisomatic ultrastructure efficiently classifies cells in mouse cortex.
Publication TypeJournal Article
Year of Publication2025
AuthorsElabbady L, Seshamani S, Mu S, Mahalingam G, Schneider-Mizell CM, Bodor AL, J Bae A, Brittain D, Buchanan JA, Bumbarger DJ, Castro MA, Dorkenwald S, Halageri A, Jia Z, Jordan C, Kapner D, Kemnitz N, Kinn S, Lee K, Li K, Lu R, Macrina T, Mitchell E, Mondal SSubhra, Nehoran B, Popovych S, Silversmith W, Takeno M, Torres R, Turner NL, Wong W, Wu J, Yin W, Yu S-C, H Seung S, R Reid C, da Costa NMaçarico, Collman F
JournalNature
Volume640
Issue8058
Pagination478-486
Date Published2025 Apr
ISSN1476-4687
KeywordsAnimals, Autoencoder, Cell Nucleus, Classification Algorithms, Datasets as Topic, DNA Primase, Male, Mice, Mice, Knockout, Microscopy, Electron, Neocortex, Neurons, Synapses
Abstract

Mammalian neocortex contains a highly diverse set of cell types. These cell types have been mapped systematically using a variety of molecular, electrophysiological and morphological approaches1-4. Each modality offers new perspectives on the variation of biological processes underlying cell-type specialization. Cellular-scale electron microscopy provides dense ultrastructural examination and an unbiased perspective on the subcellular organization of brain cells, including their synaptic connectivity and nanometre-scale morphology. In data that contain tens of thousands of neurons, most of which have incomplete reconstructions, identifying cell types becomes a clear challenge for analysis5. Here, to address this challenge, we present a systematic survey of the somatic region of all cells in a cubic millimetre of cortex using quantitative features obtained from electron microscopy. This analysis demonstrates that the perisomatic region is sufficient to identify cell types, including types defined primarily on the basis of their connectivity patterns. We then describe how this classification facilitates cell-type-specific connectivity characterization and locating cells with rare connectivity patterns in the dataset.

DOI10.1038/s41586-024-07765-7
Alternate JournalNature
PubMed ID40205216
PubMed Central IDPMC11981918
Grant ListRF1 MH123400 / MH / NIMH NIH HHS / United States
RF1 MH125932 / MH / NIMH NIH HHS / United States
RF1 MH117808 / MH / NIMH NIH HHS / United States
U24 NS126935 / NS / NINDS NIH HHS / United States
RF1 MH129268 / MH / NIMH NIH HHS / United States