Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex

Author:

Chartrand Thomas1ORCID,Dalley Rachel1ORCID,Close Jennie1ORCID,Goriounova Natalia A.2ORCID,Lee Brian R.1ORCID,Mann Rusty1ORCID,Miller Jeremy A.1ORCID,Molnar Gabor3ORCID,Mukora Alice1ORCID,Alfiler Lauren1ORCID,Baker Katherine1ORCID,Bakken Trygve E.1ORCID,Berg Jim1ORCID,Bertagnolli Darren1ORCID,Braun Thomas4ORCID,Brouner Krissy1ORCID,Casper Tamara1ORCID,Csajbok Eva Adrienn3ORCID,Dee Nick1ORCID,Egdorf Tom1ORCID,Enstrom Rachel1ORCID,Galakhova Anna A.2ORCID,Gary Amanda1ORCID,Gelfand Emily1ORCID,Goldy Jeff1ORCID,Hadley Kristen1ORCID,Heistek Tim S.2,Hill DiJon1ORCID,Jorstad Nik1ORCID,Kim Lisa1ORCID,Kocsis Agnes Katalin3ORCID,Kruse Lauren1ORCID,Kunst Michael1ORCID,Leon Gabriela1,Long Brian1ORCID,Mallory Matthew1ORCID,McGraw Medea1ORCID,McMillen Delissa1ORCID,Melief Erica J.5ORCID,Mihut Norbert3,Ng Lindsay1ORCID,Nyhus Julie1ORCID,Oláh Gáspár3ORCID,Ozsvár Attila3,Omstead Victoria1ORCID,Peterfi Zoltan3,Pom Alice1ORCID,Potekhina Lydia1ORCID,Rajanbabu Ramkumar1ORCID,Rozsa Marton3ORCID,Ruiz Augustin1ORCID,Sandle Joanna3,Sunkin Susan M.1ORCID,Szots Ildiko3ORCID,Tieu Michael1ORCID,Toth Martin3ORCID,Trinh Jessica1ORCID,Vargas Sara1,Vumbaco David1ORCID,Williams Grace1ORCID,Wilson Julia1,Yao Zizhen1ORCID,Barzo Pal6ORCID,Cobbs Charles7ORCID,Ellenbogen Richard G.8ORCID,Esposito Luke1ORCID,Ferreira Manuel8,Gouwens Nathan W.1,Grannan Benjamin8ORCID,Gwinn Ryder P.7ORCID,Hauptman Jason S.8,Jarsky Tim1ORCID,Keene C. Dirk5ORCID,Ko Andrew L.8ORCID,Koch Christof1ORCID,Ojemann Jeffrey G.8ORCID,Patel Anoop8,Ruzevick Jacob8,Silbergeld Daniel L.8,Smith Kimberly1ORCID,Sorensen Staci A.1,Tasic Bosiljka1ORCID,Ting Jonathan T.1910ORCID,Waters Jack1ORCID,de Kock Christiaan P.J.2ORCID,Mansvelder Huib D.2ORCID,Tamas Gabor3ORCID,Zeng Hongkui1ORCID,Kalmbach Brian19ORCID,Lein Ed S.18ORCID

Affiliation:

1. Allen Institute for Brain Science, Seattle, WA, USA.

2. Center for Neurogenomics and Cognitive Research, Vrije Universiteit, Amsterdam, Netherlands.

3. Research Group for Cortical Microcircuits of the Hungarian Academy of Science, University of Szeged, Szeged, Hungary.

4. byte physics, Berlin, Germany.

5. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.

6. Department of Neurosurgery, University of Szeged, Szeged, Hungary.

7. Swedish Neuroscience Institute, Seattle, WA, USA.

8. Department of Neurological Surgery, University of Washington, Seattle, WA, USA.

9. Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.

10. Washington National Primate Research Center, University of Washington, Seattle, WA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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