Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons

doi:10.1016/j.neuron.2021.08.030

Neuron

Volume 109, Issue 18, 15 September 2021, Pages 2914-2927.e5

https://doi.org/10.1016/j.neuron.2021.08.030 Get rights and content

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Highlights

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Species differences in the relative density of L5 ET neurons: mouse > macaque > human
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Correspondence between physiological and transcriptomic definition of L5 classes
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Human L5 ET dendrites display electrogenesis during direct electrical recordings
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Many conserved and divergent properties of human and rodent L5 ET neurons

Summary

In the neocortex, subcerebral axonal projections originate largely from layer 5 (L5) extratelencephalic-projecting (ET) neurons. The unique morpho-electric properties of these neurons have been mainly described in rodents, where retrograde tracers or transgenic lines can label them. Similar labeling strategies are infeasible in the human neocortex, rendering the translational relevance of findings in rodents unclear. We leveraged the recent discovery of a transcriptomically defined L5 ET neuron type to study the properties of human L5 ET neurons in neocortical brain slices derived from neurosurgeries. Patch-seq recordings, where transcriptome, physiology, and morphology were assayed from the same cell, revealed many conserved morpho-electric properties of human and rodent L5 ET neurons. Divergent properties were often subtler than differences between L5 cell types within these two species. These data suggest a conserved function of L5 ET neurons in the neocortical hierarchy but also highlight phenotypic divergence possibly related to functional specialization of human neocortex.

Graphical abstract

Keywords

human

pyramidal neuron

patch-seq

patch-clamp physiology

transcriptomics

dendrite

intrinsic membrane properties

cross-species

gene expression

dendritic spike

Data and code availability

Raw single-cell RNA-seq data from patch-seq experiments will be deposited at dbGAP. In addition, gene counts from patch-seq samples have been deposited at https://portal.brain-map.org/explore/classes/multimodal-characterization/human-l5-et-it and are publicly available as of the date of publication. These identifiers are also listed in the key resources table. SWC files from morphological reconstructions have been deposited at Brain Image Library and are publicly available at the time of publication. Identifiers are listed in the key resource table. Physiology data and mFISH data reported in this paper will be shared by the lead contact upon request.

Analysis code has been deposited at Zenodo and is publicly available as of the date of publication. DOIs are listed in the key resources table.

Any additional information required to reanalyze the data reported in this paper is available from the Lead Contract upon request.

Cited by (0)

¹⁰: Present address: Center for Neuroscience, University of California at Davis, Davis, CA 95618, USA

¹¹: Present address: Allen Institute for Immunology, Seattle, WA 98109, USA

¹²: Lead contact