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Cited by 125Neuroscience and Neuropharmacology ResearchSingle-cell and spatial transcriptomicsNeural dynamics and brain function

Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex

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Lee, Brian R., Dalley, Rachel, Miller, Jeremy A., Chartrand, Thomas, Close, Jennie, Mann, Rusty, Mukora, Alice, Ng, Lindsay +93 more·2023·Science
DOI 10.1126/science.adf6484PMC PMC12229143

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Abstract

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid–producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

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  • BICCN and BICAN reference classifications provide a foundational reference to understand the cellular, molecular and epigenomic underpinnings of AD.

    “These reference classifications provide an extremely powerful foundational reference to understand the cellular, molecular and epigenomic underpinnings of AD.”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [21]

    The Discussion describes transcriptomic cell-type taxonomies as a “starting foundation” for understanding human brain cell types, and the Abstract says further characterization is needed for insights into disease. Neither passage identifies BICCN or BICAN classifications or connects them specifically to the cellular, molecular, and epigenomic underpinnings of Alzheimer’s disease. (LLM, conf=0.84)

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  • The typical morphoelectrical properties of MGE supertypes were recently characterized using patch-seq profiling in neurosurgically resected tissues from human donors without AD, and the supragranular localization of vulnerable Sst and Pvalb interneurons was qualitatively confirmed.

    “The typical morphoelectrical properties (that is, before disease onset) of the MGE supertypes were recently characterized using patch-seq profiling in neurosurgically resected tissues from human donors without AD21,22; the supragranular localization of vulnerable Sst and Pvalb interneurons was qualitatively confirmed.”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [21]

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Cited by

Sorted by citations

  • Integrated multimodal cell atlas of Alzheimer’s disease

    Gabitto, M. I., Travaglini, K. J., Rachleff, V. M., Kaplan, E. S., Long, B., Ariza, J., Ding, Y., Mahoney, J. T., Dee, N., Goldy, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01774-5 · Cited by 397 · see citing works

    “…properties (that is, before disease onset) of the MGE supertypes were recently characterized using patch-seq profiling in neurosurgically resected tissues from human donors without AD 21,22 ; the supragranular localization of vulnerable Sst and Pvalb interneurons was qualitatively confirmed.”
    InfluentialSelf-citation

Authors
Lee, B. R., Dalley, R., Miller, J. A., Chartrand, T., Close, J., Mann, R., Mukora, A., Ng, L., Alfiler, L., Baker, K., Bertagnolli, D., Brouner, K., Casper, T., Csajbok, E., Donadio, N., Driessens, S. L. W., Egdorf, T., Enstrom, R., Galakhova, A. A., Gary, A., Gelfand, E., Goldy, J., Hadley, K., Heistek, T. S., Hill, D., Hou, W.-H., Johansen, N., Jorstad, N., Kim, L., Kocsis, A. K., Kruse, L., Kunst, M., León, G., Long, B., Mallory, M., Maxwell, M., McGraw, M., McMillen, D., Melief, E. J., Molnar, G., Mortrud, M. T., Newman, D., Nyhus, J., Opitz-Araya, X., Ozsvár, A., Pham, T., Pom, A., Potekhina, L., Rajanbabu, R., Ruiz, A., Sunkin, S. M., Szöts, I., Taskin, N., Thyagarajan, B., Tieu, M., Trinh, J., Vargas, S., Vumbaco, D., Waleboer, F., Walling-Bell, S., Weed, N., Williams, G., Wilson, J., Yao, S., Zhou, T., Barzó, P., Bakken, T., Cobbs, C., Dee, N., Ellenbogen, R. G., Esposito, L., Ferreira, M., Gouwens, N. W., Grannan, B., Gwinn, R. P., Hauptman, J. S., Hodge, R., Jarsky, T., Keene, C. D., Ko, A. L., Korshoej, A. R., Levi, B. P., Meier, K., Ojemann, J. G., Patel, A., Ruzevick, J., Silbergeld, D. L., Smith, K., Sørensen, J. C., Waters, J., Zeng, H., Berg, J., Capogna, M., Goriounova, N. A., Kalmbach, B., de Kock, C. P. J., Mansvelder, H. D., Sorensen, S. A., Tamas, G., Lein, E. S., & Ting, J. T.
Affiliations
  • Allen Institute for Brain Science (US)
  • MTA-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy, and Neuroscience, University of Szeged, 6726 Szeged, Hungary.
  • Vrije Universiteit Amsterdam (NL)
  • Aarhus University (DK)
  • Allen Institute for Brain Science, Seattle, WA 98109, USA.
  • University of Szeged (HU)
  • University of Washington (US)
  • Swedish Medical Center (US)
  • Aarhus University Hospital (DK)
  • Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), Vrije Universiteit, Amsterdam, 1081 HV, Netherlands.
Corresponding author
  • Lee, Brian R.
  • Dalley, Rachel
  • Lein, Ed S.
  • Ting, Jonathan T.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2023-10-13
Volume
382
Issue
6667
Pages
eadf6484-eadf6484
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.adf6484
PMC
PMC12229143
OpenAlex
W4387568442
Cited by
125
References
24
Citations by year
2026: 27 · 2025: 43 · 2024: 44 · 2023: 11
FWCI
15.16
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Science (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
  • PubMed (publishedVersion)
  • VU Research Portal (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (acceptedVersion, other-oa)
  • PubMed Central (acceptedVersion)
  • SZTE Publicatio Repozitórium (University of Szeged) (submittedVersion, other-oa)
Funders
  • Nancy and Buster Alvord Endowment
  • European Commission (ÚNKP-20-5, 20391-3/2018/FEKUSTRAT, HORIZON2020, 945539)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (024.004.012, OCENW.M20.285, VI.Vidi.213.014, OCENW.M20)
  • Hungarian Scientific Research Fund
  • Lundbeckfonden (R325-2019-1490)
  • Nemzeti Kutatási Fejlesztési és Innovációs Hivatal (OTKA K128863, 20391-3/2018/FEKUSTRAT)
  • H. Lundbeck A/S
  • Szegedi Tudományegyetem
  • National Institutes of Health (5u01mh114812-03, 1rf1mh128778-01, 945539, 20391-3, U01MH114812)
  • Horizon 2020 Framework Programme (#945539)
  • National Institute of Mental Health (945539, R01MH116247, U01MH114812, RF1MH114126, UG3MH120095, RF1 MH128778)
  • HORIZON EUROPE European Research Council (101093198)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
GABAergic interneurons, human neocortex, somatostatin interneurons, Patch-seq, human-mouse comparison, neuronal morphology, electrophysiology
MeSH terms
Animals, gamma-Aminobutyric Acid, Humans, Interneurons, Patch-Clamp Techniques, Neocortex, Mice, Electrophysiological Phenomena, GABAergic Neurons

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