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 language | English |
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Article number | eadf0805 |
Pages (from-to) | 1-19 |
Number of pages | 19 |
Journal | Science (New York, N.Y.) |
Volume | 382 |
Issue number | 6667 |
Early online date | Oct 2023 |
DOIs | |
Publication status | Published - 13 Oct 2023 |
Bibliographical note
Special Issue Research ArticleFunding
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.).
Funders | Funder number |
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ELKH-SZTE | KÖ-36/2021 |
ENW-M2 | M20.285, 945539 |
European Union’s Horizon 2020 Framework Programme for Research and Innovation | VI.Vidi.213.014, 024.004.012 |
Hungarian Ministry of Culture and Innovation | |
Ministry of Human Capacities Hungary | 20391-3/2018/FEKUSTRAT |
National Academy of Scientist Education Program of the National Biomedical Foundation | |
National Institutes of Health | U01MH114812, 1RF1MH128778 |
National Institute of Mental Health | KKP133807 |
Nancy and Buster Alvord Endowment | |
Allen Institute | |
European Research Council | 101093198 |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Magyar Tudományos Akadémia | |
Nemzeti Kutatási Fejlesztési és Innovációs Hivatal | ÚNKP-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 |