Connectomic comparison of mouse and human cortex

Loomba, Sahil; Straehle, Jakob; Gangadharan, Vijayvan; Heike, Natalie; Khalifa, Abdelrahman; Motta, Alessandro; Ju, Niansheng; Sievers, Meike; Gempt, Jens; Meyer, Hanno S.; Helmstaedter, Moritz

doi:10.1126/science.abo0924

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Connectomic comparison of mouse and human cortex

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Loomba, Sahil
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;
Faculty of Science, Radboud University, Nijmegen, Netherlands.;

Straehle, Jakob
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;
Department of Neurosurgery, University Freiburg, Freiburg, Germany. ;

Gangadharan, Vijayvan
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

Heike, Natalie
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

Khalifa, Abdelrahman
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

Motta, Alessandro
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

Ju, Niansheng
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

Sievers, Meike
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;
Faculty of Science, Radboud University, Nijmegen, Netherlands.;

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Helmstaedter, Moritz
Connectomics Department, Max Planck Institute for Brain Research, Max Planck Society;

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Citation

Loomba, S., Straehle, J., Gangadharan, V., Heike, N., Khalifa, A., Motta, A., et al. (2022). Connectomic comparison of mouse and human cortex. Science, 377(6602): eabo0924. doi:10.1126/science.abo0924.

Cite as: https://hdl.handle.net/21.11116/0000-0009-D0AF-7

Abstract

The human cerebral cortex houses 1000 times more neurons than that of the cerebral cortex of a mouse, but the possible differences in synaptic circuits between these species are still poorly understood. We used three-dimensional electron microscopy of mouse, macaque, and human cortical samples to study their cell type composition and synaptic circuit architecture. The 2.5-fold increase in interneurons in humans compared with mice was compensated by a change in axonal connection probabilities and therefore did not yield a commensurate increase in inhibitory-versus-excitatory synaptic input balance on human pyramidal cells. Rather, increased inhibition created an expanded interneuron-to-interneuron network, driven by an expansion of interneuron-targeting interneuron types and an increase in their synaptic selectivity for interneuron innervation. These constitute key neuronal network alterations in the human cortex.