1. Human neocortical expansion involves glutamatergic neuron diversification.
- Author
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Berg J, Sorensen SA, Ting JT, Miller JA, Chartrand T, Buchin A, Bakken TE, Budzillo A, Dee N, Ding SL, Gouwens NW, Hodge RD, Kalmbach B, Lee C, Lee BR, Alfiler L, Baker K, Barkan E, Beller A, Berry K, Bertagnolli D, Bickley K, Bomben J, Braun T, Brouner K, Casper T, Chong P, Crichton K, Dalley R, de Frates R, Desta T, Lee SD, D'Orazi F, Dotson N, Egdorf T, Enstrom R, Farrell C, Feng D, Fong O, Furdan S, Galakhova AA, Gamlin C, Gary A, Glandon A, Goldy J, Gorham M, Goriounova NA, Gratiy S, Graybuck L, Gu H, Hadley K, Hansen N, Heistek TS, Henry AM, Heyer DB, Hill D, Hill C, Hupp M, Jarsky T, Kebede S, Keene L, Kim L, Kim MH, Kroll M, Latimer C, Levi BP, Link KE, Mallory M, Mann R, Marshall D, Maxwell M, McGraw M, McMillen D, Melief E, Mertens EJ, Mezei L, Mihut N, Mok S, Molnar G, Mukora A, Ng L, Ngo K, Nicovich PR, Nyhus J, Olah G, Oldre A, Omstead V, Ozsvar A, Park D, Peng H, Pham T, Pom CA, Potekhina L, Rajanbabu R, Ransford S, Reid D, Rimorin C, Ruiz A, Sandman D, Sulc J, Sunkin SM, Szafer A, Szemenyei V, Thomsen ER, Tieu M, Torkelson A, Trinh J, Tung H, Wakeman W, Waleboer F, Ward K, Wilbers R, Williams G, Yao Z, Yoon JG, Anastassiou C, Arkhipov A, Barzo P, Bernard A, Cobbs C, de Witt Hamer PC, Ellenbogen RG, Esposito L, Ferreira M, Gwinn RP, Hawrylycz MJ, Hof PR, Idema S, Jones AR, Keene CD, Ko AL, Murphy GJ, Ng L, Ojemann JG, Patel AP, Phillips JW, Silbergeld DL, Smith K, Tasic B, Yuste R, Segev I, de Kock CPJ, Mansvelder HD, Tamas G, Zeng H, Koch C, and Lein ES
- Subjects
- Alzheimer Disease, Animals, Cell Shape, Collagen metabolism, Electrophysiology, Extracellular Matrix Proteins metabolism, Female, Humans, Lysine analogs & derivatives, Male, Mice, Neocortex anatomy & histology, Neurons classification, Patch-Clamp Techniques, Transcriptome, Glutamic Acid metabolism, Neocortex cytology, Neocortex growth & development, Neurons cytology, Neurons metabolism
- Abstract
The neocortex is disproportionately expanded in human compared with mouse
1,2 , 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., (© 2021. The Author(s).)- Published
- 2021
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