Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex

Lee, B.; Dalley, R.; Miller, J. A.; Chartrand, T.; Close, J.; Mann, R.; Mukora, A.; Ng, L.; Alfiler, L.; Baker, K.; Bertagnolli, D.; Brouner, K.; Casper, T.; Csajbok, E.; Dee, N.; Donadio, N.; Driessens, S. L. W.; Egdorf, T.; Enstrom, R.; Galakhova, A. A.; Gary, A.; Gelfand, E.; Goldy, J.; Hadley, K.; Heistek, T. S.; Hill, D.; Johansen, N.; Jorstad, N.; Kim, L.; Kocsis, A. K.; Kruse, L.; Kunst, M.; Leon, G.; Long, B.; Mallory, M.; Maxwell, M.; McGraw, M.; McMillen, D.; Melief, E. J.; Molnar, G.; Mortrud, M. T.; Newman, D.; Nyhus, J.; Opitz-Araya, X.; Pham, T.; Pom, A.; Potekhina, L.; Rajanbabu

doi:10.1101/2022.11.08.515739

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bioRxiv · 10.1101/2022.11.08.515739

Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex

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Abstract

Human cortical interneurons have been challenging to study due to high diversity and lack of mature brain tissue platforms and genetic targeting tools. We employed rapid GABAergic neuron viral labeling plus unbiased Patch-seq sampling in brain slices to define the signature morpho-electric properties of GABAergic neurons in the human neocortex. Viral targeting greatly facilitated sampling of the SST subclass, including primate specialized double bouquet cells which mapped to two SST transcriptomic types. Multimodal analysis uncovered an SST neuron type with properties inconsistent with original subclass assignment; we instead propose reclassification into PVALB subclass. Our findings provide novel insights about functional properties of human cortical GABAergic neuron subclasses and types and highlight the essential role of multimodal annotation for refinement of emerging transcriptomic cell type taxonomies. One Sentence SummaryViral genetic labeling of GABAergic neurons in human ex vivo brain slices paired with Patch-seq recording yields an in-depth functional annotation of human cortical interneuron subclasses and types and highlights the essential role of multimodal functional annotation for refinement of emerging transcriptomic cell type taxonomies.

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Lee, B., Dalley, R., Miller, J. A., Chartrand, T., Close, J., Mann, R., Mukora, A., Ng, L., Alfiler, L., Baker, K., Bertagnolli, D., Brouner, K., Casper, T., Csajbok, E., Dee, N., Donadio, N., Driessens, S. L. W., Egdorf, T., Enstrom, R., Galakhova, A. A., Gary, A., Gelfand, E., Goldy, J., Hadley, K., Heistek, T. S., Hill, D., Johansen, N., Jorstad, N., Kim, L., Kocsis, A. K., Kruse, L., Kunst, M., Leon, G., Long, B., Mallory, M., Maxwell, M., McGraw, M., McMillen, D., Melief, E. J., Molnar, G., Mortrud, M. T., Newman, D., Nyhus, J., Opitz-Araya, X., Pham, T., Pom, A., Potekhina, L., Rajanbabu. 2022-11-09. Signature morpho-electric properties of diverse GABAergic interneurons in the human neocortex. https://doi.org/10.1101/2022.11.08.515739

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