小柯机器人

西湖大学生命科学学院贾洁敏团队发现，神经轴突与小动脉平滑肌细胞(aSMCs)之间的突触样传递驱动脑神经血管耦合(NVC)。该研究于2024年1月2日发表于国际一流学术期刊《自然—神经科学》杂志上。

他们利用小鼠大脑皮层的双光子局点光遗传学，证明了单个谷氨酸能轴突通过神经-小动脉平滑肌细胞连接(NsMJs)之间的突触样传递来扩张其支配神经的小动脉。突触前亲本-子代按钮在突触后树突和aSMCs上形成双重神经支配，aSMCs表达多种类型的神经介质受体，包括低水平的谷氨酸NMDA受体亚基1 (Grin1)。通过aSMC特异性敲除GluN1破坏NsMJ的传递，可减少光遗传和须刺激引起的功能性充血。

值得注意的是，aSMCs中GluN1亚基的缺失通过防止由缺血诱导的扩张性去极化引起的小动脉收缩期间aSMCs中的Ca2+超载来减少脑缺血后的脑萎缩。他们的研究结果揭示了NsMJ传播驱动NVC，并为中风研究开辟了新的途径。

据悉，NVC对脑功能至关重要，其功能障碍是许多神经病理的基础。尽管细胞类型特异性与NVC有关，但活跃的神经信息如何传递到大脑中的目标小动脉仍然知之甚少。

附：英文原文

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

Author: Zhang, Dongdong, Ruan, Jiayu, Peng, Shiyu, Li, Jinze, Hu, Xu, Zhang, Yiyi, Zhang, Tianrui, Ge, Yaping, Zhu, Zhu, Xiao, Xian, Zhu, Yunxu, Li, Xuzhao, Li, Tingbo, Zhou, Lili, Gao, Qingzhu, Zheng, Guoxiao, Zhao, Bingrui, Li, Xiangqing, Zhu, Yanming, Wu, Jinsong, Li, Wensheng, Zhao, Jingwei, Ge, Woo-ping, Xu, Tian, Jia, Jie-Min

Issue&Volume: 2024-01-02

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.

DOI: 10.1038/s41593-023-01515-0

Source: https://www.nature.com/articles/s41593-023-01515-0

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex