Perisomatic ultrastructure efficiently classifies cells in mouse cortex

Leila Elabbady, Sharmishtaa Seshamani, Shang Mu, Gayathri Mahalingam, Casey M. Schneider-Mizell, Agnes L. Bodor, J. Alexander Bae, Derrick Brittain, JoAnn Buchanan, Daniel J. Bumbarger, Manuel A. Castro, Sven Dorkenwald, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Eric Mitchell, Shanka Subhra Mondal, Barak Nehoran, Sergiy Popovych, William Silversmith, Marc Takeno, Russel Torres, Nicholas L. Turner, William Wong, Jingpeng Wu, Wenjing Yin, Szi-chieh Yu, H. Sebastian Seung, R. Clay Reid, Nuno Maçarico Costa and Forrest Collman ()
Additional contact information
Leila Elabbady: Allen Institute for Brain Science
Sharmishtaa Seshamani: Allen Institute for Brain Science
Shang Mu: Princeton University
Gayathri Mahalingam: Allen Institute for Brain Science
Casey M. Schneider-Mizell: Allen Institute for Brain Science
Agnes L. Bodor: Allen Institute for Brain Science
J. Alexander Bae: Princeton University
Derrick Brittain: Allen Institute for Brain Science
JoAnn Buchanan: Allen Institute for Brain Science
Daniel J. Bumbarger: Allen Institute for Brain Science
Manuel A. Castro: Princeton University
Sven Dorkenwald: Allen Institute for Brain Science
Akhilesh Halageri: Princeton University
Zhen Jia: Princeton University
Chris Jordan: Princeton University
Dan Kapner: Allen Institute for Brain Science
Nico Kemnitz: Princeton University
Sam Kinn: Allen Institute for Brain Science
Kisuk Lee: Princeton University
Kai Li: Princeton University
Ran Lu: Princeton University
Thomas Macrina: Princeton University
Eric Mitchell: Princeton University
Shanka Subhra Mondal: Princeton University
Barak Nehoran: Princeton University
Sergiy Popovych: Princeton University
William Silversmith: Princeton University
Marc Takeno: Allen Institute for Brain Science
Russel Torres: Allen Institute for Brain Science
Nicholas L. Turner: Princeton University
William Wong: Princeton University
Jingpeng Wu: Princeton University
Wenjing Yin: Allen Institute for Brain Science
Szi-chieh Yu: Princeton University
H. Sebastian Seung: Princeton University
R. Clay Reid: Allen Institute for Brain Science
Nuno Maçarico Costa: Allen Institute for Brain Science
Forrest Collman: Allen Institute for Brain Science

Nature, 2025, vol. 640, issue 8058, 478-486

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41586-024-07765-7

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