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 R. Lee, Rusty Mann, Jeremy A. Miller, Gabor Molnar, Alice Mukora, Lauren Alfiler, Katherine Baker, Trygve E. Bakken, Jim Berg, Darren Bertagnolli, Thomas Braun, Krissy Brouner, Tamara Casper, Eva Adrienn Csajbok, Nick Dee, Tom EgdorfRachel Enstrom, Anna A. Galakhova, Amanda Gary, Emily Gelfand, Jeff Goldy, Kristen Hadley, Tim S. Heistek, Di Jon Hill, Nik Jorstad, Lisa Kim, Agnes Katalin Kocsis, Lauren Kruse, Michael Kunst, Gabriela Leon, Brian Long, Matthew Mallory, Medea McGraw, Delissa McMillen, Erica J. Melief, Norbert Mihut, Lindsay Ng, Julie Nyhus, Gáspár Oláh, Attila Ozsvár, Victoria Omstead, Zoltan Peterfi, Alice Pom, Lydia Potekhina, Ramkumar Rajanbabu, Marton Rozsa, Augustin Ruiz, Joanna Sandle, Susan M. Sunkin, Ildiko Szots, Michael Tieu, Martin Toth, Jessica Trinh, Sara Vargas, David Vumbaco, Grace Williams, Julia Wilson, Zizhen Yao, Pal Barzo, Charles Cobbs, Richard G. Ellenbogen, Luke Esposito, Manuel Ferreira, Nathan W. Gouwens, Benjamin Grannan, Ryder P. Gwinn, Jason S. Hauptman, Tim Jarsky, C. Dirk Keene, Andrew L. Ko, Christof Koch, Jeffrey G. Ojemann, Anoop Patel, Jacob Ruzevick, Daniel L. Silbergeld, Kimberly Smith, Staci A. Sorensen, Bosiljka Tasic, Jonathan T. Ting, Jack Waters, Christiaan P.J. de Kock, Huib D. Mansvelder, Gabor Tamas, Hongkui Zeng, Brian Kalmbach, Ed S. Lein

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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.

Original languageEnglish
Article numbereadf0805
Pages (from-to)1-19
Number of pages19
JournalScience (New York, N.Y.)
Volume382
Issue number6667
Early online dateOct 2023
DOIs
Publication statusPublished - 13 Oct 2023

Bibliographical note

Special Issue Research Article

Funding

We thank the Allen Institute founder, Paul G. Allen, for his vision, encouragement, and support. This publication was supported by and coordinated through the Brain Initiative Cell Census Network (BICCN). This publication is part of the Human Cell Atlas: www. humancellatlas.org/publications/. This work was funded in part by NIH award U01MH114812 (to E.S.L.) and 1RF1MH128778 (to S.A.S.) from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH and its subsidiary institutes. This work was also funded in part by KKP_20 Élvonal KKP133807, Ministry of Human Capacities Hungary (20391-3/2018/FEKUSTRAT) (to G.T.); Eötvös Loránd Research Network grants ELKH-SZTE (G.T.) Agykérgi Neuronhálózatok Kutatócsoport and KÖ-36/2021 (G.T.); National Research, Development and Innovation Office grants GINOP 2.3.2-15-2016-00018 (G.T.), ÚNKP-20-5-SZTE-681 (GT), 2019-2.1.7-ERA-NET-2022-00038 (G.T.), TKP-2021-EGA-09 (G.T.), TKP-2021-EGA-28 (G.T.), and ÚNKP-21-5-SZTE-580 New National Excellence Program of the Ministry for Innovation and Technology (to G.M.); János Bolyai Research Scholarship of the Hungarian Academy of Sciences (G.M.); the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation (to J.S.); the Dutch Research Council (NWO) Open Competition (ENW-M2) grant OCENW. M20.285 (to C.P.J.d.K.); grant 945539 (Human Brain Project SGA3) from the European Union’s Horizon 2020 Framework Programme for Research and Innovation (to H.D.M. and N.A.G.); the NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology grant 024.004.012 (H.D.M. and N.A.G.); NWO grant VI.Vidi.213.014 (H.D.M. and N.A.G.); European Research Council advanced grant “fasthumanneuron” 101093198 (to H.D.M.); and the Nancy and Buster Alvord Endowment (to C.D.K.).

FundersFunder number
ELKH-SZTEKÖ-36/2021
ENW-M2M20.285, 945539
European Union’s Horizon 2020 Framework Programme for Research and InnovationVI.Vidi.213.014, 024.004.012
Hungarian Ministry of Culture and Innovation
Ministry of Human Capacities Hungary20391-3/2018/FEKUSTRAT
National Academy of Scientist Education Program of the National Biomedical Foundation
National Institutes of HealthU01MH114812, 1RF1MH128778
National Institute of Mental HealthKKP133807
Nancy and Buster Alvord Endowment
Allen Institute
European Research Council101093198
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Magyar Tudományos Akadémia
Nemzeti Kutatási Fejlesztési és Innovációs HivatalÚNKP-21-5-SZTE-580, 2019-2.1.7-ERA-NET-2022-00038, TKP-2021-EGA-28, TKP-2021-EGA-09, ÚNKP-20-5-SZTE-681, GINOP 2.3.2-15-2016-00018
Innovációs és Technológiai Minisztérium

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