Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex
Brian R. Lee, Rachel Dalley, Jeremy A. Miller, Thomas Chartrand, Jennie Close, Rusty Mann, Alice Mukora, Lindsay Ng, Lauren Alfiler, Katherine Baker, Darren Bertagnolli, Krissy Brouner, Tamara Casper, Eva Csajbok, Nicholas Donadio, Stan L.W. Driessens, Tom Egdorf, Rachel Enstrom, Anna A. Galakhova, Amanda Gary, Emily Gelfand, Jeff Goldy, Kristen Hadley, Tim S. Heistek, Dijon Hill, Wen-Hsien Hou, Nelson Johansen, Nik Jorstad, Lisa Kim, Agnes Katalin Kocsis, Lauren, Kruse, Michael Kunst, Gabriela León, Brian Long, Matthew Mallory, Michelle Maxwell, Medea McGraw, Delissa McMillen, Erica J. Melief, Gabor Molnar, Marty T. Mortrud, Dakota Newman, Julie Nyhus, Ximena Opitz-Araya, Attila Ozsvár, Trangthanh Pham, Alice Pom, Lydia Potekhina, Ram Rajanbabu, Augustin Ruiz, Susan M. Sunkin, Ildikó Szöts, Naz Taskin, Bargavi Thyagarajan, Michael Tieu, Jessica Trinh, Sara Vargas, David Vumbaco, Femke Waleboer, Sarah Walling-Bell, Natalie Weed, Grace Williams, Julia Wilson, Shenqin Yao, Thomas Zhou, Pál Barzó, Trygve Bakken, Charles Cobbs, Nick Dee, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Nathan W. Gouwens, Benjamin Grannan, Ryder P. Gwinn, Jason S. Hauptman, Rebecca Hodge, Tim Jarsky, C. Dirk Keene, Andrew L. Ko, Anders Rosendal Korshoej, Boaz P. Levi, Kaare Meier, Jeffrey G. Ojemann, Anoop Patel, Jacob Ruzevick, Daniel L. Silbergeld, Kimberly Smith, Jens Christian Sørensen, Jack Waters, Hongkui Zeng, Jim Berg, Marco Capogna, Natalia A. Goriounova, Brian Kalmbach, Christiaan P.J. de Kock, Huib D. Mansvelder, Staci A. Sorensen, Gabor Tamas, Ed S. Lein, and Jonathan T. Ting
Science (2023)
Abstract
Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid–producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.