Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex
Thomas Chartrand, Rachel Dalley, Jennie Close, Natalia A. Goriounova, Brian Lee, Rusty Mann, Jeremy A. Miller, Gábor Molnár, Alice Mukora, Lauren Alfiler, Katherine Baker, Trygve E. Bakken, Jim Berg, Darren Bertagnolli, Thomas Braun, Krissy Brouner, Tamara Casper, Éva Csajbók, Nick Dee, Tom Egdorf, Rachel Enstrom, Anna A. Galakhova, Amanda Gary, Emily Gelfand, Jeff Goldy, Kristen Hadley, Tim S. Heistek, DiJon Hill, Nik Jorstad, Lisa Kim, Agnes Katalin Kocsis, Lauren Kruse, Michael Kunst, Gabriela León, Brian Long, Matthew Mallory, Mary McGraw, Delissa McMillen, Erica J. Melief, Norbert Mihut, Lindsay Ng, Julie Nyhus, Gáspár Oláh, Attila Ozsvár, Victoria Omstead, Zoltán Péterfi, Christina Alice Pom, Lydia Potekhina, Ramkumar Rajanbabu, Márton Rózsa, Augustin Ruiz, Joanna Sandle, Susan M. Sunkin, Ildikó Szöts, Michael Tieu, Martin Tóth, Jessica Trinh, Sara Vargas, David Vumbaco, Grace Williams, Julia Wilson, Zizhen Yao, Pál Barzó, Charles Cobbs, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Nathan W. Gouwens, Benjamin L. Grannan, Ryder P. Gwinn, Jason S. Hauptman, Tim Jarsky, C. Dirk Keene, Andrew L. Ko, Christof Koch, Jeffrey G. Ojemann, Anoop P. Patel, Jacob Ruzevick, Daniel L. Silbergeld, Kimberly A. Smith, Staci A. Sorensen, Bosiljka Tasic, Jonathan T. Ting, Jack Waters, Christiaan P. J. de Kock, Huibert D. Mansvelder, Gábor Tamás, Hongkui Zeng, Brian Kalmbach, Ed S. Lein
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.