Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Neuron. 2018 Dec 5;100(5):1133-1148.e3. doi: 10.1016/j.neuron.2018.09.045. Epub 2018 Oct 25.
Dynamic changes in astrocyte free Ca regulate synaptic signaling and local blood flow. Although astrocytes are poised to integrate signals from synapses and the vasculature to perform their functional roles, it remains unclear what dictates astrocyte responses during neurovascular coupling under realistic conditions. We examined peri-arteriole and peri-capillary astrocytes in the barrel cortex of active mice in response to sensory stimulation or volitional behaviors. We observed an AMPA and NMDA receptor-dependent elevation in astrocyte endfoot Ca that followed functional hyperemia onset. This delayed astrocyte Ca signal was dependent on the animal's action at the time of measurement as well as a neurovascular pathway that linked to endothelial-derived nitric oxide. A similar elevation in endfoot Ca was evoked using vascular chemogenetics or optogenetics, and opto-stimulated dilation recruited the same nitric oxide pathway as functional hyperemia. These data show that behavioral state and microvasculature influence astrocyte Ca in active mice. VIDEO ABSTRACT.
星形胶质细胞内游离 Ca 的动态变化调节着突触信号和局部血流。尽管星形胶质细胞准备整合来自突触和脉管系统的信号以发挥其功能作用，但在现实条件下，什么决定了神经血管耦联期间星形胶质细胞的反应仍不清楚。我们观察了活跃小鼠的桶状皮层中动脉周围和毛细血管周围星形胶质细胞对感觉刺激或随意行为的反应。我们观察到星形胶质细胞足突 Ca 的 AMPA 和 NMDA 受体依赖性升高，这与功能性充血的开始相吻合。这种延迟的星形胶质细胞 Ca 信号依赖于动物在测量时的动作以及与内皮衍生的一氧化氮相联系的神经血管途径。使用血管化学遗传学或光遗传学可以诱发类似的足突 Ca 升高，而光刺激引起的扩张招募了与功能性充血相同的一氧化氮途径。这些数据表明，行为状态和微血管影响活跃小鼠的星形胶质细胞 Ca。视频摘要。
