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  3. Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling

  • Nat Neurosci. 2024 Jan 2. doi: 10.1038/s41593-023-01515-0.
Dongdong Zhang 1 2 3 4 5,  Jiayu Ruan 2 3 4 5,  Shiyu Peng 2 4,  Jinze Li 2 3 4 5,  Xu Hu 2 3 4 5,  Yiyi Zhang 2 3 4 5,  Tianrui Zhang 5,  Yaping Ge 2 3 4 5,  Zhu Zhu 2 3 4 5,  Xian Xiao 2 3,  Yunxu Zhu 5,  Xuzhao Li 2 3 4 5,  Tingbo Li 2 3 4 5,  Lili Zhou 2 3 4 5,  Qingzhu Gao 5,  Guoxiao Zheng 3,  Bingrui Zhao 2 3 4 5,  Xiangqing Li 6,  Yanming Zhu 7 8,  Jinsong Wu 9 10 11 12 13,  Wensheng Li 14,  Jingwei Zhao 15,  Woo-Ping Ge 16,  Tian Xu 2 4,  Jie-Min Jia 17 18 19 20
Affiliations

Affiliations

  • 1 School of Life Sciences, Fudan University, Shanghai, China.
  • 2 Key Laboratory of Growth Regulation and Translation Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.
  • 3 Laboratory of Neurovascular Biology, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China.
  • 4 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
  • 5 Laboratory of Neurovascular Biology, School of Life Sciences, Westlake University, Hangzhou, China.
  • 6 College of Artificial Intelligence and Big Data for Medical Sciences, Shandong Academy of Medical Sciences, Shandong First Medical University, Jinan, China.
  • 7 Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • 8 Program in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, USA.
  • 9 Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
  • 10 Brain Function Laboratory, Neurosurgical Institute of Fudan University, Shanghai, China.
  • 11 Institute of Brain-Intelligence Technology, Zhangjiang Lab, Shanghai, China, Shanghai, China.
  • 12 Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China.
  • 13 Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
  • 14 Department of Anatomy, Histology, and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
  • 15 Department of Anatomy, Histology, and Embryology, Research Center of Systemic Medicine, School of Basic Medicine, and Department of Pathology of the Sir Run-Run Shaw Hospital, The Cryo-EM Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
  • 16 Chinese Institute for Brain Research, Beijing, Beijing, China.
  • 17 Key Laboratory of Growth Regulation and Translation Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. jiajiemin@westlake.edu.cn.
  • 18 Laboratory of Neurovascular Biology, Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China. jiajiemin@westlake.edu.cn.
  • 19 Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. jiajiemin@westlake.edu.cn.
  • 20 Laboratory of Neurovascular Biology, School of Life Sciences, Westlake University, Hangzhou, China. jiajiemin@westlake.edu.cn.
PMID: 38168932 DOI: 10.1038/s41593-023-01515-0
Abstract

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA Receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing CA2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

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