Connectomic comparison of mouse and human cortex

• Published in: Science (American Association for the Advancement of Science) 2022-07, Vol.377 (6602), p.eabo0924-eabo0924
• Main Authors: Loomba, Sahil, Straehle, Jakob, Gangadharan, Vijayan, Heike, Natalie, Khalifa, Abdelrahman, Motta, Alessandro, Ju, Niansheng, Sievers, Meike, Gempt, Jens, Meyer, Hanno S., Helmstaedter, Moritz
• Format: Article
• Language: English
• Subjects: Biopsy; Brain; Brain research; Cerebral cortex; Circuits; Configurations; Cortex (frontal); Cortex (parietal); Data acquisition; Divergence; Electron microscopy; Epilepsy; Evolution; Homology; Human tissues; Innervation; Interneurons; Introduced species; Ion channels; Mental disorders; Microscopy; Nervous system; Networks; Neural networks; Neurons; Neurosurgery; Pyramidal cells; Similarity; Species; Substantia grisea; Surgery; Synapses; Temporal lobe; Thickening; Transcriptomics; Tumors
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abo0924

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. Over the past few decades, the mouse has become a model organism for brain research. Because of the close evolutionary similarity of ion channels, synaptic receptors, and other key molecular constituents of the brain to that of humans, corresponding similarity has been assumed for cortical neuronal circuits. However, comparative synaptic-resolution connectomic studies are required to determine the degree to which circuit structure has evolved between species. Using three-dimensional electron microscopy, Loomba et al . compared mouse and human/macaque cortex synaptic connectivity. Although human cells are much larger compared with mouse neurons and are more numerous, on average, they do not receive more synapses. And, even though there are three times more interneurons in the human cortex than in the mouse, the excitation-to-inhibition ratio is similar between the species. —PRS Three-dimensional electron microscopy of mouse, macaque, and human brain samples elucidates cell type composition and synaptic circuit architecture.