BIL Logo Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons

[ DOI: https://doi.org/10.35077/g.19 ]

 

Dataset Citation:
Lein, Ed, Berg, Jim, Sorensen, Staci, Ting, Jonathan. (2020). Human cortical expansion involves diversification and specialization of supragranular intratelencephalic-projecting neurons. [ Collection / Dataset ]. Brain Image Library. https://doi.org/10.35077/g.19

 

Abstract:
The neocortex is disproportionately expanded in human compared to mouse, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers that selectively make connections within the cortex and other telencephalic structures. Single-cell transcriptomic analyses of human and mouse cortex show an increased diversity of glutamatergic neuron types in supragranular cortex in human and pronounced gradients as a function of cortical depth. To probe the functional and anatomical correlates of this transcriptomic diversity, we describe a robust Patch-seq platform using neurosurgically-resected human tissues. We characterize the morphological and physiological properties of five transcriptomically defined human glutamatergic supragranular neuron types. Three of these types have properties that are specialized compared to the more homogeneous properties of transcriptomically defined homologous mouse neuron types. The two remaining supragranular neuron types, located exclusively in deep layer 3, do not have clear mouse homologues in supragranular cortex but are transcriptionally most similar to deep layer mouse intratelencephalic-projecting neuron types. Furthermore, we reveal the transcriptomic types in deep layer 3 that express high levels of non-phosphorylated heavy chain neurofilament protein that label long-range neurons known to be selectively depleted in Alzheimer’s disease. Together, these results demonstrate the power of transcriptomic cell type classification, provide a mechanistic underpinning for increased complexity of cortical function in human cortical evolution, and implicate discrete transcriptomic cell types as selectively vulnerable in disease.

 

Methods:
Experimental protocols are available on protocols.io via the links listed below. Detailed descriptions of experiemntal data collection methods are also available at help.brain-map.org/display/celltypes/Documentation. Human Neurosurgical Tissue Processing: dx.doi.org/10.17504/protocols.io.bf66jrhe Patch-Seq Internal Solution with Biocytin: dx.doi.org/10.17504/protocols.io.besdjea6 Patch-Seq Recording and Extraction: dx.doi.org/10.17504/protocols.io.bepyjdpw Post Patch Clamp Slice Fixation: dx.doi.org/10.17504/protocols.io.bg5tjy6n DAB Detection of Biocytin Labeled Tissue: dx.doi.org/10.17504/protocols.io.bg5yjy7w 20X Anatomic and Layer Identification for Biocytin Filled Cells: dx.doi.org/10.17504/protocols.io.bey9jfz6

 

Funding:
National Institutes of Mental Health U01-MH114812 A MULTIMODAL ATLAS OF HUMAN BRAIN CELL TYPES;
Allen Institute for Brain Science ;
National Eye Institute R01-EY023173 HIGH-THROUGHPUT ROBOTIC ANALYSIS OF INTEGRATED NEURONAL PHENOTYPES;
National Institutes of Mental Health U01-MH105982 ESTABLISHING A COMPREHENSIVE AND STANDARDIZED CELL TYPE CHARACTERIZATION PLATFORM

 

Contributors:
Lein, Ed (ContactPerson) [ORCID: http://orcid.org/0000-0001-9012-6552 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Lein, Ed (ProjectLeader) [ORCID: http://orcid.org/0000-0001-9012-6552 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Berg, Jim (ContactPerson) [ORCID: http://orcid.org/0000-0002-3300-5399 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Berg, Jim (Researcher) [ORCID: http://orcid.org/0000-0002-3300-5399 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Berg, Jim (ProjectMember) [ORCID: http://orcid.org/0000-0002-3300-5399 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Sorensen, Staci (Researcher) [ORCID: http://orcid.org/0000-0002-6799-2126 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Sorensen, Staci (ProjectMember) [ORCID: http://orcid.org/0000-0002-6799-2126 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Ting, Jonathan (Researcher) [ORCID: http://orcid.org/0000-0001-8266-0392 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
Ting, Jonathan (ProjectMember) [ORCID: http://orcid.org/0000-0001-8266-0392 ] Allen Institute for Brain Science [ROR: https://ror.org/00dcv1019];
University of Szeged (ResearchGroup) University of Szeged [ROR: https://ror.org/01pnej532];
Tamas, Gabor (ProjectLeader) [ORCID: http://orcid.org/0000-0002-7905-6001 ] University of Szeged [ROR: https://ror.org/01pnej532];
Vrije Universiteit Amsterdam (ResearchGroup) Vrije Universiteit Amsterdam [ROR: https://ror.org/008xxew50];
Mansvelder, Huibert (ProjectLeader) [ORCID: http://orcid.org/0000-0003-1365-5340 ] Vrije Universiteit Amsterdam [ROR: https://ror.org/008xxew50];
The Hebrew University Jerusalem (ResearchGroup) The Hebrew University Jerusalem [ROR: https://ror.org/03qxff017];
Segev, Idan (ProjectLeader) [ORCID: http://orcid.org/0000-0001-7279-9630 ] The Hebrew University Jerusalem [ROR: https://ror.org/03qxff017]

 

Related Identifiers:
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IsDocumentedBy [ DOI : https://dx.doi.org/10.17504/protocols.io.bg5yjy7w ];
IsDocumentedBy [ DOI : https://dx.doi.org/10.17504/protocols.io.bey9jfz6 ];
IsDocumentedBy [ URL : https://help.brain-map.org/display/celltypes/Documentation ];