Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Thomas Chartrand(Allen Institute for Brain Science), Rachel Dalley(Allen Institute for Brain Science), Jennie Close(Allen Institute for Brain Science), Natalia A. Goriounova(Vrije Universiteit Amsterdam), Brian Lee(Allen Institute for Brain Science), Rusty Mann(Allen Institute for Brain Science), Jeremy A. Miller(Allen Institute for Brain Science), Gábor Molnár(University of Szeged), Alice Mukora(Allen Institute for Brain Science), Lauren Alfiler(Allen Institute for Brain Science), Katherine Baker(Allen Institute for Brain Science), Trygve E. Bakken(Allen Institute for Brain Science), Jim Berg(Allen Institute for Brain Science), Darren Bertagnolli(Allen Institute for Brain Science), Thomas Braun, Krissy Brouner(Allen Institute for Brain Science), Tamara Casper(Allen Institute for Brain Science), Éva Csajbók(University of Szeged), Nick Dee(Allen Institute for Brain Science), Tom Egdorf(Allen Institute for Brain Science), Rachel Enstrom(Allen Institute for Brain Science), Anna A. Galakhova(Vrije Universiteit Amsterdam), 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(Vrije Universiteit Amsterdam), DiJon Hill(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), Mary McGraw(Allen Institute for Brain Science), Delissa McMillen(Allen Institute for Brain Science), Erica J. Melief(University of Washington), Norbert Mihut(University of Szeged), Lindsay Ng(Allen Institute for Brain Science), Julie Nyhus(Allen Institute for Brain Science), Gáspár Oláh(University of Szeged), Attila Ozsvár(University of Szeged), Victoria Omstead(Allen Institute for Brain Science), Zoltán Péterfi(University of Szeged), Christina Alice Pom(Allen Institute for Brain Science), Lydia Potekhina(Allen Institute for Brain Science), Ramkumar Rajanbabu(Allen Institute for Brain Science), Márton Rózsa(University of Szeged), Augustin Ruiz(Allen Institute for Brain Science), Joanna Sandle(University of Szeged), Susan M. Sunkin(Allen Institute for Brain Science), Ildikó Szöts(University of Szeged), Michael Tieu(Allen Institute for Brain Science), Martin Tóth(University of Szeged), Jessica Trinh(Allen Institute for Brain Science), Sara Vargas(Allen Institute for Brain Science), David Vumbaco(Allen Institute for Brain Science), Grace Williams(Allen Institute for Brain Science), Julia Wilson(Allen Institute for Brain Science), Zizhen Yao(Allen Institute for Brain Science), Pál Barzó(University of Szeged), Charles Cobbs(Swedish Medical Center), 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), Tim Jarsky(Allen Institute for Brain Science), C. Dirk Keene(University of Washington), Andrew L. Ko(University of Washington), Christof Koch(Allen Institute for Brain Science), 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), Staci A. Sorensen(Allen Institute for Brain Science), Bosiljka Tasic(Allen Institute for Brain Science), Jonathan T. Ting(Allen Institute for Brain Science), Jack Waters(Allen Institute for Brain Science), Christiaan P. J. de Kock(Vrije Universiteit Amsterdam), Huibert D. Mansvelder(Vrije Universiteit Amsterdam), Gábor Tamás(University of Szeged), Hongkui Zeng(Allen Institute for Brain Science), Brian Kalmbach(Allen Institute for Brain Science), Ed S. Lein(Allen Institute for Brain Science)
Cited by 81Open Access
Abstract
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.
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