Published in

Nature Research, Nature, 7879(598), p. 151-158, 2021

DOI: 10.1038/s41586-021-03813-8

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Human neocortical expansion involves glutamatergic neuron diversification

Journal article published in 2021 by Jim Berg ORCID, Staci A. Sorensen, Jonathan T. Ting, Jeremy A. Miller ORCID, Thomas Chartrand, Anatoly Buchin, Trygve E. Bakken ORCID, Agata Budzillo ORCID, Nick Dee, Song-Lin Ding, Nathan W. Gouwens ORCID, Rebecca D. Hodge ORCID, Brian Kalmbach ORCID, Changkyu Lee, Brian R. Lee and other authors.
This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

AbstractThe 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.