RT Journal Article SR Electronic T1 Large-scale unsupervised discovery of excitatory morphological cell types in mouse visual cortex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.12.22.521541 DO 10.1101/2022.12.22.521541 A1 Marissa A. Weis A1 Stelios Papadopoulos A1 Laura Hansel A1 Timo Lüddecke A1 Brendan Celii A1 Paul G. Fahey A1 J. Alexander Bae A1 Agnes L. Bodor A1 Derrick Brittain A1 JoAnn Buchanan A1 Daniel J. Bumbarger A1 Manuel A. Castro A1 Erick Cobos A1 Forrest Collman A1 Nuno Maçarico da Costa A1 Sven Dorkenwald A1 Leila Elabbady A1 Emmanouil Froudarakis A1 Akhilesh Halageri A1 Zhen Jia A1 Chris Jordan A1 Dan Kapner A1 Nico Kemnitz A1 Sam Kinn A1 Kisuk Lee A1 Kai Li A1 Ran Lu A1 Thomas Macrina A1 Gayathri Mahalingam A1 Eric Mitchell A1 Shanka Subhra Mondal A1 Shang Mu A1 Barak Nehoran A1 Saumil Patel A1 Xaq Pitkow A1 Sergiy Popovych A1 R. Clay Reid A1 Casey M. Schneider-Mizell A1 H. Sebastian Seung A1 William Silversmith A1 Fabian H. Sinz A1 Marc Takeno A1 Russel Torres A1 Nicholas L. Turner A1 William Wong A1 Jingpeng Wu A1 Wenjing Yin A1 Szi-chieh Yu A1 Jacob Reimer A1 Andreas S. Tolias A1 Alexander S. Ecker YR 2022 UL http://biorxiv.org/content/early/2022/12/22/2022.12.22.521541.abstract AB Neurons in the neocortex exhibit astonishing morphological diversity which is critical for properly wiring neural circuits and giving neurons their functional properties. The extent to which the morphological diversity of excitatory neurons forms a continuum or is built from distinct clusters of cell types remains 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 a millimeter scale serial-section electron microscopy volume. We found a set of principles that captured the morphological diversity of the dendrites of excitatory neurons. First, their morphologies varied with respect to three major axes: soma depth, total apical and basal skeletal length. Second, neurons in layer 2/3 showed a strong trend of a decreasing width of their dendritic arbor and a smaller tuft with increasing cortical depth. Third, in layer 4, atufted neurons were primarily located in the primary visual cortex, while tufted neurons were more abundant in higher visual areas. Fourth, we discovered layer 4 neurons in V1 on the border to layer 5 which showed a tendency towards avoiding deeper layers with their dendrites. In summary, excitatory neurons exhibited a substantial degree of dendritic morphological variation, both within and across cortical layers, but this variation mostly formed a continuum, with only a few notable exceptions in deeper layers.Competing Interest StatementThe authors have declared no competing interest.