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Central nervous system atlas of larval zebrafish constructed using the morphology of single excitatory and inhibitory neurons

Du, X.; Yue, Z.; Chen, M.; Li, W.; Chen, T.; Hu, H.; Wan, H.; Zhao, T.; Zhong, Y.; Ning, X.; Zheng, X.; Ren, H.; Wang, R.; Zhao, R.; Peng, X.; Jia, Z.; Jin, C.; Huang, J.; Deng, W.; Qian, L.; Wang, L.; Zheng, M.; Zhang, W.; Shen, X.; Shen, X.; Qiu, X.; Zhao, Q.; Li, D.; Chen, L.; Wang, S.; Gong, Y.; Li, Y.; Mu, Y.; Ji, P.; He, J.; Wang, Y.; Du, J.

2025-08-22 neuroscience
10.1101/2025.06.06.658008 bioRxiv
Show abstract

Comprehensive single-neuron morphology mapping is fundamental to deciphering the brain architecture and function. While invertebrate animal models including Caenorhabditis elegans and Drosophila melanogaster have achieved complete neuronal maps primarily via electron microscopy reconstructions1-8, vertebrate efforts remain limited in spatial coverage and/or lack of cell type annotation9-18. Here, we present a nervous system-wide, cellular-resolution neuronal morphology atlas for the vertebrate animal model of larval zebrafish, annotated with excitatory (E) and inhibitory (I) neurotransmitter identity and dendrite-axon polarity. The dataset, collected from over 13,400 individual animals, encompasses more than 20,000 neurons spanning the brain, spinal cord, and peripheral ganglia (covering [~] 25% of all E and I neurons in the brain), all integrated into a whole-body common physical space with detailed neuroanatomical parcellations. It reveals over 500 hierarchically classified neuronal morphotypes and enables the construction of directed and weighted inter-cell-type and interregional connectomes, bridging large-scale cellular anatomy with circuit- and system-level organization across spatial scales. Neuronal projection analyses reveal differences between E and I neurons in ipsilateral-contralateral and ascending-descending projection preferences, the combination of projection modes for bilateral innervation, and the modular organization of projection patterns. Network analyses identify structured connectivity motifs, network hubs, and characteristic multimodal sensorimotor pathways. Hosted on the open interactive platform ZExplorer, this resource enables exploration, querying, and integration of multimodal neural data, laying a foundation for understanding functional circuits, developing models, and conducting hypothesis-driven research of the zebrafish brain.

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