bioRxiv (Cold Spring Harbor Laboratory)·202222 cites
20222026
22
Lee, Brian 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 Dee, Nick 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 Johansen, Nelson and Jorstad, Nik and Kim, Lisa and Kocsis, Agnes Katalin and Kruse, Lauren and Kunst, Michael and Leon, 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 Pham, Trangthanh and Pom, Alice and Potekhina, Lydia and Rajanbabu, Ram and Ruiz, Augustin and Sunkin, Susan M and Szots, Ildiko and Taskin, Naz and Thyagarajan, Bargavi and Tieu, Michael and Trinh, Jessica and Vargas, Sara and Vumbaco, David and Waleboer, Femke and Weed, Natalie and Williams, Grace and Wilson, Julia and Yao, Shenqin and Zhou, Thomas and Barzo, Pal and Bakken, Trygve and Cobbs, Charles 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 Levi, Boaz and Ojemann, Jeffrey G. and Patel, Anoop and Ruzevick, Jacob and Silbergeld, Daniel L. and Smith, Kim and Waters, Jack and Zeng, Hongkui and Berg, Jim 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 cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in brain slices to define the signature morpho-electric properties of GABAergic neurons in the human neocortex. Viral targeting greatly facilitated sampling of the SST subclass, including primate specialized double bouquet cells which mapped to two SST transcriptomic types. Multimodal analysis uncovered an SST neuron type with properties inconsistent with original subclass assignment; we instead propose reclassification into PVALB subclass. Our findings provide novel insights about functional properties of human cortical GABAergic neuron subclasses and types and highlight the essential role of multimodal annotation for refinement of emerging transcriptomic cell type taxonomies. One Sentence Summary Viral genetic labeling of GABAergic neurons in human ex vivo brain slices paired with Patch-seq recording yields an in-depth functional annotation of human cortical interneuron subclasses and types and highlights the essential role of multimodal functional annotation for refinement of emerging transcriptomic cell type taxonomies.
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