Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex

Science 2023 116 cites
2023:122024:272025:372026:40
2023 2026
116

Lee, Brian R. and Dalley, Rachel and Miller, Jeremy A. and Chartrand, Thomas and Close, Jennie and Mann, Rusty and Mukora, Alice and Ng, Lindsay and Alfiler, Lauren and Baker, Katherine and Bertagnolli, Darren and Brouner, Krissy and Casper, Tamara and Csajbok, Eva and Donadio, Nicholas and Driessens, Stan L.W. and Egdorf, Tom and Enstrom, Rachel and Galakhova, Anna A. and Gary, Amanda and Gelfand, Emily and Goldy, Jeff and Hadley, Kristen and Heistek, Tim S. and Hill, Dijon and Hou, Wen-Hsien and Johansen, Nelson and Jorstad, Nik and Kim, Lisa and Kocsis, Agnes Katalin and Kruse, Lauren and Kunst, Michael and Le\'{o}n, Gabriela and Long, Brian and Mallory, Matthew and Maxwell, Michelle and McGraw, Medea and McMillen, Delissa and Melief, Erica J. and Molnar, Gabor and Mortrud, Marty T. and Newman, Dakota and Nyhus, Julie and Opitz-Araya, Ximena and Ozsv\'{a}r, Attila and Pham, Trangthanh and Pom, Alice and Potekhina, Lydia and Rajanbabu, Ram and Ruiz, Augustin and Sunkin, Susan M. and Sz\"{o}ts, Ildik\'{o} and Taskin, Naz and Thyagarajan, Bargavi and Tieu, Michael and Trinh, Jessica and Vargas, Sara and Vumbaco, David and Waleboer, Femke and Walling-Bell, Sarah and Weed, Natalie and Williams, Grace and Wilson, Julia and Yao, Shenqin and Zhou, Thomas and Barz\'{o}, P\'{a}l and Bakken, Trygve and Cobbs, Charles and Dee, Nick and Ellenbogen, Richard G. and Esposito, Luke and Ferreira, Manuel and Gouwens, Nathan W. and Grannan, Benjamin and Gwinn, Ryder P. and Hauptman, Jason S. and Hodge, Rebecca and Jarsky, Tim and Keene, C. Dirk and Ko, Andrew L. and Korshoej, Anders Rosendal and Levi, Boaz P. and Meier, Kaare and Ojemann, Jeffrey G. and Patel, Anoop and Ruzevick, Jacob and Silbergeld, Daniel L. and Smith, Kimberly and S\o{}rensen, Jens Christian and Waters, Jack and Zeng, Hongkui and Berg, Jim and Capogna, Marco and Goriounova, Natalia A. and Kalmbach, Brian and de Kock, Christiaan P.J. and Mansvelder, Huib D. and Sorensen, Staci A. and Tamas, Gabor and Lein, Ed S. and Ting, Jonathan T.

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.

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