Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Nature neuroscience - 27(2024), 2 vom: 13. Feb., Seite 232-248 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Dongdong [VerfasserIn] |
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| Anmerkungen: |
Date Completed 14.02.2024 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41593-023-01515-0 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366595601 |
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| 245 | 1 | 0 | |a Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling |
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| 520 | |a 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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| 700 | 1 | |a Peng, Shiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jinze |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tianrui |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Yaping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhu |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Xian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yunxu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xuzhao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Tingbo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Lili |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qingzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Guoxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Bingrui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiangqing |e verfasserin |4 aut | |
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| 700 | 1 | |a Xu, Tian |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Jie-Min |e verfasserin |4 aut | |
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