Human neocortical expansion involves glutamatergic neuron diversification.


Jim Berg
Staci A Sorensen
Jonathan T Ting
Jeremy A Miller
Thomas Chartrand
Anatoly Buchin
Trygve E Bakken
Agata Budzillo
Nick Dee
Song-Lin Ding
Nathan W Gouwens
Rebecca D Hodge
Brian Kalmbach
Changkyu Lee
Brian R Lee
Lauren Alfiler
Katherine Baker
Eliza Barkan
Allison Beller
Kyla Berry
Darren Bertagnolli
Kris Bickley
Jasmine Bomben
Thomas Braun
Krissy Brouner
Tamara Casper
Peter Chong
Kirsten Crichton
Rachel Dalley
Rebecca de Frates
Tsega Desta
Samuel Dingman Lee
Florence D'Orazi
Nadezhda Dotson
Tom Egdorf
Rachel Enstrom
Colin Farrell
David Feng
Olivia Fong
Szabina Furdan
Anna A Galakhova
Clare Gamlin
Amanda Gary
Alexandra Glandon
Jeff Goldy
Melissa Gorham
Natalia A Goriounova
Sergey Gratiy
Lucas Graybuck
Hong Gu
Kristen Hadley
Nathan Hansen, Swedish Neuroscience Institute, Seattle, WA, USAFollow
Tim S Heistek
Alex M Henry
Djai B Heyer
DiJon Hill
Chris Hill
Madie Hupp
Tim Jarsky
Sara Kebede
Lisa Keene
Lisa Kim
Mean-Hwan Kim
Matthew Kroll
Caitlin Latimer
Boaz P Levi
Katherine E Link
Matthew Mallory
Rusty Mann
Desiree Marshall
Michelle Maxwell
Medea McGraw
Delissa McMillen
Erica Melief
Eline J Mertens
Leona Mezei
Norbert Mihut
Stephanie Mok
Gabor Molnar
Alice Mukora
Lindsay Ng
Kiet Ngo
Philip R Nicovich
Julie Nyhus
Gaspar Olah
Aaron Oldre
Victoria Omstead
Attila Ozsvar
Daniel Park
Hanchuan Peng
Trangthanh Pham
Christina A Pom
Lydia Potekhina
Ramkumar Rajanbabu
Shea Ransford
David Reid
Christine Rimorin
Augustin Ruiz
David Sandman
Josef Sulc
Susan M Sunkin
Aaron Szafer
Viktor Szemenyei
Elliot R Thomsen
Michael Tieu
Amy Torkelson
Jessica Trinh
Herman Tung
Wayne Wakeman
Femke Waleboer
Katelyn Ward
René Wilbers
Grace Williams
Zizhen Yao
Jae-Guen Yoon, Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, WA 98122, USAFollow
Costas Anastassiou
Anton Arkhipov
Pal Barzo
Amy Bernard
Charles Cobbs, The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience InstituteFollow
Philip C de Witt Hamer
Richard G Ellenbogen
Luke Esposito
Manuel Ferreira
Ryder P Gwinn, Swedish Neuroscience Institute, Seattle, WA, USAFollow
Michael J Hawrylycz
Patrick R Hof
Sander Idema
Allan R Jones
C Dirk Keene
Andrew L Ko
Gabe J Murphy
Lydia Ng
Jeffrey G Ojemann
Anoop P Patel
John W Phillips
Daniel L Silbergeld
Kimberly Smith
Bosiljka Tasic
Rafael Yuste
Idan Segev
Christiaan P J de Kock
Huibert D Mansvelder
Gabor Tamas
Hongkui Zeng
Christof Koch
Ed S Lein

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washington; seattle; swedish; swedish neurosci; Alzheimer Disease; Animals; Cell Shape; Collagen; Electrophysiology; Extracellular Matrix Proteins; Female; Glutamic Acid; Humans; Lysine; Male; Mice; Neocortex; Neurons; Patch-Clamp Techniques; Transcriptome


The neocortex is disproportionately expanded in human compared with mouse1,2, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth3. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease4,5. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.

Clinical Institute

Neurosciences (Brain & Spine)