Inhibitory specificity from a connectomic census of mouse visual cortex

• 成果类型: Article
• 署名作者: Schneider-Mizell, Casey M.; Bodor, Agnes L.; Brittain, Derrick; Buchanan, Joann; Bumbarger, Daniel J.; Elabbady, Leila; Gamlin, Clare; Kapner, Daniel; Kinn, Sam; Mahalingam, Gayathri; Seshamani, Sharmishtaa; Suckow, Shelby; Takeno, Marc; Torres, Russel; Yin, Wenjing; Dorkenwald, Sven; Bae, J. Alexander; Castro, Manuel A.; Halageri, Akhilesh; Jia, Zhen; Jordan, Chris; Kemnitz, Nico; Lee, Kisuk; Li, Kai; Lu, Ran; Macrina, Thomas; Mitchell, Eric; Mondal, Shanka Subhra; Mu, Shang; Nehoran, Barak; Popovych, Sergiy; Silversmith, William; Turner, Nicholas L.; Wong, William; Wu, Jingpeng; Reimer, Jacob; Tolias, Andreas S.; Seung, H. Sebastian; Reid, R. Clay; Collman, Forrest; da Costa, Nuno Macarico
• 署名单位: Allen Institute for Brain Science; Princeton University; Princeton University; Princeton University; Rice University; Baylor College of Medicine; Baylor College of Medicine; Massachusetts Institute of Technology (MIT)
• 刊物名称: Nature
• ISSN/ISSBN: 0028-2358
• DOI: 10.1038/s41586-024-07780-8
• 发表日期: 2025-04-10
• 关键词: cell-types; gabaergic interneurons; connectivity; circuits; neurons

摘要

Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties1. Synaptic connectivity shapes how each cell type participates in the cortical circuit, but mapping connectivity rules at the resolution of distinct cell types remains difficult. Here we used millimetre-scale volumetric electron microscopy2 to investigate the connectivity of all inhibitory neurons across a densely segmented neuronal population of 1,352 cells spanning all layers of mouse visual cortex, producing a wiring diagram of inhibition with more than 70,000 synapses. Inspired by classical neuroanatomy, we classified inhibitory neurons based on targeting of dendritic compartments and developed an excitatory neuron classification based on dendritic reconstructions with whole-cell maps of synaptic input. Single-cell connectivity showed a class of disinhibitory specialist that targets basket cells. Analysis of inhibitory connectivity onto excitatory neurons found widespread specificity, with many interneurons exhibiting differential targeting of spatially intermingled subpopulations. Inhibitory targeting was organized into 'motif groups', diverse sets of cells that collectively target both perisomatic and dendritic compartments of the same excitatory targets. Collectively, our analysis identified new organizing principles for cortical inhibition and will serve as a foundation for linking contemporary multimodal neuronal atlases with the cortical wiring diagram.