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1. Toward an Integrated Classification of Cell Types: Morphoelectric and Transcriptomic Characterization of Individual GABAergic Cortical Neurons

Author

Kimberly A. Smith, Matthew Kroll, Sara Kebede, Susan M. Sunkin, David Reid, Nadezhda Dotson, Rusty Mann, DiJon Hill, Kara Ronellenfitch, Shea Ransford, Hongkui Zeng, David Feng, Jasmine Bomben, Bosiljka Tasic, Rachel Enstrom, Jessica Trinh, Matthew Mallory, Aaron Szafer, Rachel A. Dalley, Aaron Oldre, Amanda Gary, Eliza Barkan, Nick Dee, Lydia Ng, Tae Kyung Kim, Ed S. Lein, Colin Farrell, Tamara Casper, Tom Egdorf, Kirsten Crichton, Josef Sulc, Fahimeh Baftizadeh, Katelyn Ward, Kirsten Hadley, Alex M. Henry, Alice Pom, Brian Lee, Uygar Sümbül, Lisa Kim, Tim Jarsky, Madie Happ, Wayne Wakeman, Lauren Ellingwood, Luke Esposito, Daniel Park, Tanya L. Daigle, Darren Bertagnolli, Lucas T. Graybuck, Olivia Fong, Philip R. Nicovich, Gabe J. Murphy, Michelle Maxwell, Lindsay Ng, Rebeeca de Frates, Rohan Gala, Alice Mukora, Delissa McMillen, Miranda Robertson, Thanh Pham, Samuel Dingman Lee, Kris Bickley, Anton Arkhipov, Osnat Penn, Staci A. Sorensen, Alexandra Glandon, Zizhen Yao, Amy Torkelson, Jonathan T. Ting, Lauren Alfiler, Ramkumar Rajanbabu, Kiet Ngo, Kirssy Brouner, David Sandman, Michael Tieu, Michael Hawrylycz, Nathan W. Gouwens, Hanchuan Peng, Zhi Zhou, Jeff Goldy, Hong Gu, Herman Tung, Medea McGraw, Lyida Potekhina, Katherine Baker, Tsega Desta, Christof Koch, Changkyu Lee, Melissa Gorham, Clare Gamlin, Augustin Ruiz, Grace Williams, Jim Berg, Kyla Berry, Katherine E. Link, Agata Budzillo, Christine Rimorin, and Thomas Braun

Subjects
Cell type, genetic structures, Interneuron, Cortical neurons, Biology, Transcriptome, Electrophysiology, medicine.anatomical_structure, Visual cortex, nervous system, medicine, biology.protein, GABAergic, Neuroscience, Parvalbumin
Abstract

Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, or genetic attributes. To better constrain the definition of neuronal cell types, we characterized the transcriptomes and intrinsic physiological properties of over 3,700 GABAergic mouse visual cortical neurons and reconstructed the local morphologies of 350 of those neurons. We found that most transcriptomic types (t-types) occupy specific laminar positions within mouse visual cortex, and many of those t-types exhibit consistent electrophysiological and morphological features. We observed that these properties could vary continuously between t- types, which limited the ability to predict specific t-types from other data modalities. Despite that, the data support the presence of at least 20 interneuron met-types that have congruent morphological, electrophysiological, and transcriptomic properties.

Published
2020

2. A Taxonomy of Transcriptomic Cell Types Across the Isocortex and Hippocampal Formation

Author

James Gray, Adriana E. Sedeno-Cortes, Michael Tieu, Songlin Ding, Michael Hawrylycz, Herman Tung, Olivia Fong, Matthew Kroll, Stephanie Mok, Zizhen Yao, Darren Bertagnolli, Fahimeh Baftizadeh, Thanh Pham, Delissa McMillen, Thuc Nghi Nguyen, Hongkui Zeng, Tamara Casper, Katelyn Ward, Emma Garren, Kimberly A. Smith, Qingzhong Ren, Christine Rimorin, Jeff Goldy, Alexandra Glandon, Kanan Lathia, Lucas T. Graybuck, Amy Torkelson, Nick Dee, Nadiya V. Shapovalova, Susan M. Sunkin, Daniel Hirschstein, Bosiljka Tasic, Kirsten Crichton, Josef Sulc, Boaz P. Levi, and Cindy T. J. van Velthoven

Subjects
Transcriptome, Cell type, Glutamatergic, Neocortex, medicine.anatomical_structure, Taxonomy (general), medicine, Hippocampus, Hippocampal formation, Biology, Neuroscience, Function (biology)
Abstract

The isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles in perception, cognition, emotion and learning. Using single-cell RNA-sequencing approaches, we profiled ~1.2 million cells covering all regions in the adult mouse isocortex and hippocampal formation. The cell types are organized hierarchically and exhibit varying degrees of discrete or continuous variations. Such molecular relationships correlate strongly with the spatial distribution patterns of the cell types, which can be region-specific, shared across multiple regions, or part of one or more gradients. Glutamatergic neuron types display much greater diversity than GABAergic neuron types, both molecularly and spatially, and define regional identities as well as inter-region relationships. Our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation for the first time, and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these two brain structures.

Published
2020

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