Single-neuron projectome reveals organization of somatosensory ascending pathways in the mouse brain

Wen-Qun Ding; Wei Song; Xiaoxue Shi; Zhao Feng; Xu Chen; Taorong Xie; Yuan Liu; Jiandong Zhou; Yu Chen; Jun-Kai Lin; Qiu-Miao Wang; Hua Zhou; Tong-Yu Liang; Tao Jiang; Biyu Ren; Haishan Yao; Yun-Qing Li; Henry C Evrard; Mu-Ming Poo; Hui Li; Xiangning Li; Hui Gong; Andrew J Todd; Anan Li; Xiaofei Wang; Juan Deng; Yan-Gang Sun

doi:10.1016/j.neuron.2025.03.007

Single-neuron projectome reveals organization of somatosensory ascending pathways in the mouse brain

Neuron. 2025 Apr 8:S0896-6273(25)00179-5. doi: 10.1016/j.neuron.2025.03.007. Online ahead of print.

Authors

Wen-Qun Ding¹, Wei Song², Xiaoxue Shi³, Zhao Feng⁴, Xu Chen⁵, Taorong Xie³, Yuan Liu³, Jiandong Zhou⁶, Yu Chen³, Jun-Kai Lin¹, Qiu-Miao Wang¹, Hua Zhou³, Tong-Yu Liang¹, Tao Jiang⁴, Biyu Ren³, Haishan Yao³, Yun-Qing Li⁷, Henry C Evrard⁸, Mu-Ming Poo³, Hui Li⁷, Xiangning Li⁹, Hui Gong¹⁰, Andrew J Todd¹¹, Anan Li¹², Xiaofei Wang¹³, Juan Deng¹⁴, Yan-Gang Sun¹⁵

Affiliations

¹ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
² Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of the Chinese Academy of Sciences, Beijing 100049, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
³ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
⁴ HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215123, China.
⁵ Lingang Laboratory, Shanghai 200031, China.
⁶ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, China.
⁷ Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Centre, the Fourth Military Medical University, Xi'an 710032, China.
⁸ International Center for Primate Brain Research, Center for Excellence in Brain Science and Intelligence, Institute of Neuroscience, Chinese Academy of Sciences, Songjiang, Shanghai, China; Werner Reichardt Center for Integrative Neuroscience, Karl Eberhard University of Tübingen, Tübingen, Germany; Max Planck Institute for Biological Cybernetics, Tübingen, Germany.
⁹ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya 572025, China.
¹⁰ HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215123, China; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, China.
¹¹ School of Psychology and Neuroscience, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
¹² HUST-Suzhou Institute for Brainsmatics, JITRI, Suzhou 215123, China; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan 430074, China; State Key Laboratory of Digital Medical Engineering, Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Sanya 572025, China. Electronic address: aali@hust.edu.cn.
¹³ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: xfwang@ion.ac.cn.
¹⁴ Department of Anesthesiology, Huashan Hospital, State Key Laboratory of Medical Neurobiology, Institute for Translational Brain Research, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: juandeng@fudan.edu.cn.
¹⁵ Institute of Neuroscience, State Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: yangang.sun@ion.ac.cn.

PMID: 40209714
DOI: 10.1016/j.neuron.2025.03.007

Abstract

Relay of multimodal somatosensory information from the spinal cord to the brain is critical for sensory perception, but the underlying circuit organization remains unclear. We have reconstructed mouse cervical spinal projection neurons at single-cell resolution and identified 19 projectome-defined subtypes exhibiting diverse projection patterns. We also reconstructed the brain-wide axonal projections of central relay neurons that receive direct spinal inputs at the single-cell resolution. We discovered parallel, divergent, and convergent projection patterns for spinal projection neurons and central relay neurons. Our results revealed the diverse pathways channeling spinal information to the cortex. Furthermore, we identified parallel lateral and medial spinal-superior colliculus-brainstem pathways, which could be involved in orienting and defensive behaviors, respectively. These data allowed us to construct a wiring diagram for ascending somatosensory pathways with projectome-defined subtype resolution. Our single-cell projectome analysis provided a new framework for understanding the complex neural circuitry underlying coordinated processing of diverse somatosensory modalities.

Keywords: ascending pathways; central relay neurons; projectome-defined subtypes; single-neuron projectome; spinal projection neurons.