An unsupervised map of excitatory neuron dendritic morphology in the mouse visual cortex.

TitleAn unsupervised map of excitatory neuron dendritic morphology in the mouse visual cortex.
Publication TypeJournal Article
Year of Publication2025
AuthorsWeis MA, Papadopoulos S, Hansel L, Lüddecke T, Celii B, Fahey PG, Wang EY, J Bae A, Bodor AL, Brittain D, Buchanan JA, Bumbarger DJ, Castro MA, Collman F, da Costa NMaçarico, Dorkenwald S, Elabbady L, Halageri A, Jia Z, Jordan C, Kapner D, Kemnitz N, Kinn S, Lee K, Li K, Lu R, Macrina T, Mahalingam G, Mitchell E, Mondal SSubhra, Mu S, Nehoran B, Popovych S, R Reid C, Schneider-Mizell CM, H Seung S, Silversmith W, Takeno M, Torres R, Turner NL, Wong W, Wu J, Yin W, Yu S-C, Reimer J, Berens P, Tolias AS, Ecker AS
JournalNat Commun
Volume16
Issue1
Pagination3361
Date Published2025 Apr 09
ISSN2041-1723
KeywordsAnimals, Dendrites, Female, Male, Mice, Mice, Inbred C57BL, Neurons, Visual Cortex
Abstract

Neurons in the neocortex exhibit astonishing morphological diversity, which is critical for properly wiring neural circuits and giving neurons their functional properties. However, the organizational principles underlying this morphological diversity remain an open question. Here, we took a data-driven approach using graph-based machine learning methods to obtain a low-dimensional morphological "bar code" describing more than 30,000 excitatory neurons in mouse visual areas V1, AL, and RL that were reconstructed from the millimeter scale MICrONS serial-section electron microscopy volume. Contrary to previous classifications into discrete morphological types (m-types), our data-driven approach suggests that the morphological landscape of cortical excitatory neurons is better described as a continuum, with a few notable exceptions in layers 5 and 6. Dendritic morphologies in layers 2-3 exhibited a trend towards a decreasing width of the dendritic arbor and a smaller tuft with increasing cortical depth. Inter-area differences were most evident in layer 4, where V1 contained more atufted neurons than higher visual areas. Moreover, we discovered neurons in V1 on the border to layer 5, which avoided deeper layers with their dendrites. In summary, we suggest that excitatory neurons' morphological diversity is better understood by considering axes of variation than using distinct m-types.

DOI10.1038/s41467-025-58763-w
Alternate JournalNat Commun
PubMed ID40204760
PubMed Central IDPMC11982532
Grant List390727645 / / Deutsche Forschungsgemeinschaft (German Research Foundation) /
D16PC00003 / / ODNI | Intelligence Advanced Research Projects Activity (IARPA) /
RF1 MH130416 / MH / NIMH NIH HHS / United States
T32-EY-002520-37 / / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) /
P30 EY002520 / EY / NEI NIH HHS / United States
101039115 / / EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) /
R01 MH109556 / MH / NIMH NIH HHS / United States
D16PC00005 / / ODNI | Intelligence Advanced Research Projects Activity (IARPA) /
U19 MH114830 / MH / NIMH NIH HHS / United States
R01 EY026927 / EY / NEI NIH HHS / United States
U19MH114830 / / U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) /
D16PC00004 / / ODNI | Intelligence Advanced Research Projects Activity (IARPA) /
101041669 / / EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) /