Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex

Brian Lee(Allen Institute for Brain Science), Rachel Dalley(Allen Institute for Brain Science), Jeremy A. Miller(Allen Institute for Brain Science), Thomas Chartrand(Allen Institute for Brain Science), Jennie Close(Allen Institute for Brain Science), Rusty Mann(Allen Institute for Brain Science), Alice Mukora(Allen Institute for Brain Science), Lindsay Ng(Allen Institute for Brain Science), Lauren Alfiler(Allen Institute for Brain Science), Katherine Baker(Allen Institute for Brain Science), Darren Bertagnolli(Allen Institute for Brain Science), Krissy Brouner(Allen Institute for Brain Science), Tamara Casper(Allen Institute for Brain Science), Éva Csajbók(University of Szeged), Nicholas Donadio(Allen Institute for Brain Science), Stan L.W. Driessens(Cognitive Research (United States)), Tom Egdorf(Allen Institute for Brain Science), Rachel Enstrom(Allen Institute for Brain Science), Anna A. Galakhova(Cognitive Research (United States)), Amanda Gary(Allen Institute for Brain Science), Emily Gelfand(Allen Institute for Brain Science), Jeff Goldy(Allen Institute for Brain Science), Kristen Hadley(Allen Institute for Brain Science), Tim S. Heistek(Cognitive Research (United States)), DiJon Hill(Allen Institute for Brain Science), Wen‐Hsien Hou(Aarhus University), Nelson Johansen(Allen Institute for Brain Science), Nik Jorstad(Allen Institute for Brain Science), Lisa Kim(Allen Institute for Brain Science), Agnes Katalin Kocsis(University of Szeged), Lauren Kruse(Allen Institute for Brain Science), Michael Kunst(Allen Institute for Brain Science), Gabriela León(Allen Institute for Brain Science), Brian Long(Allen Institute for Brain Science), Matthew Mallory(Allen Institute for Brain Science), Michelle Maxwell(Allen Institute for Brain Science), Mary McGraw(Allen Institute for Brain Science), Delissa McMillen(Allen Institute for Brain Science), Erica J. Melief(University of Washington), Gábor Molnár(University of Szeged), Marty Mortrud(Allen Institute for Brain Science), Dakota Newman(Allen Institute for Brain Science), Julie Nyhus(Allen Institute for Brain Science), Ximena Opitz-Araya(Allen Institute for Brain Science), Attila Ozsvár(Aarhus University), Trangthanh Pham(Allen Institute for Brain Science), Christina Alice Pom(Allen Institute for Brain Science), Lydia Potekhina(Allen Institute for Brain Science), Ram Rajanbabu(Allen Institute for Brain Science), Augustin Ruiz(Allen Institute for Brain Science), Susan M. Sunkin(Allen Institute for Brain Science), Ildikó Szöts(University of Szeged), Naz Taskin(Allen Institute for Brain Science), Bargavi Thyagarajan(Allen Institute for Brain Science), Michael Tieu(Allen Institute for Brain Science), Jessica Trinh(Allen Institute for Brain Science), Sara Vargas(Allen Institute for Brain Science), David Vumbaco(Allen Institute for Brain Science), Femke Waleboer(Cognitive Research (United States)), Sarah Walling-Bell(Allen Institute for Brain Science), Natalie Weed(Allen Institute for Brain Science), Grace Williams(Allen Institute for Brain Science), Julia Wilson(Allen Institute for Brain Science), Shenqin Yao(Allen Institute for Brain Science), Tingfa Zhou(Allen Institute for Brain Science), Pál Barzó(University of Szeged), Trygve E. Bakken(Allen Institute for Brain Science), Charles Cobbs(Swedish Medical Center), Nick Dee(Allen Institute for Brain Science), Richard G. Ellenbogen(University of Washington), Luke Esposito(Allen Institute for Brain Science), Manuel Ferreira(University of Washington), Nathan W. Gouwens(Allen Institute for Brain Science), Benjamin L. Grannan(University of Washington), Ryder P. Gwinn(Swedish Medical Center), Jason S. Hauptman(University of Washington), Rebecca D. Hodge(Allen Institute for Brain Science), Tim Jarsky(Allen Institute for Brain Science), C. Dirk Keene(University of Washington), Andrew L. Ko(University of Washington), Anders Rosendal Korshoej(Aarhus University Hospital), Boaz P. Levi(Allen Institute for Brain Science), Kaare Meier(Aarhus University Hospital), Jeffrey G. Ojemann(University of Washington), Anoop P. Patel(University of Washington), Jacob Ruzevick(University of Washington), Daniel L. Silbergeld(University of Washington), Kimberly A. Smith(Allen Institute for Brain Science), Jens Christian Hedemann Sørensen(Aarhus University Hospital), Jack Waters(Allen Institute for Brain Science), Hongkui Zeng(Allen Institute for Brain Science), Jim Berg(Allen Institute for Brain Science), Marco Capogna(Aarhus University), Natalia A. Goriounova(Cognitive Research (United States)), Brian Kalmbach(Allen Institute for Brain Science), Christiaan P. J. de Kock(Cognitive Research (United States)), Huibert D. Mansvelder(Cognitive Research (United States)), Staci A. Sorensen(Allen Institute for Brain Science), Gábor Tamás(University of Szeged), Ed S. Lein(Allen Institute for Brain Science), Jonathan T. Ting(Allen Institute for Brain Science)
Science
October 12, 2023
Cited by 118Open Access
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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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