Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, 89557-352, USA.
Nat Commun. 2022 Dec 22;13(1):7872. doi: 10.1038/s41467-022-35383-2.
Functional hyperemia occurs when enhanced neuronal activity signals to increase local cerebral blood flow (CBF) to satisfy regional energy demand. Ca elevation in astrocytes can drive arteriole dilation to increase CBF, yet affirmative evidence for the necessity of astrocytes in functional hyperemia in vivo is lacking. In awake mice, we discovered that functional hyperemia is bimodal with a distinct early and late component whereby arteriole dilation progresses as sensory stimulation is sustained. Clamping astrocyte Ca signaling in vivo by expressing a plasma membrane Ca ATPase (CalEx) reduces sustained but not brief sensory-evoked arteriole dilation. Elevating astrocyte free Ca using chemogenetics selectively augments sustained hyperemia. Antagonizing NMDA-receptors or epoxyeicosatrienoic acid production reduces only the late component of functional hyperemia, leaving brief increases in CBF to sensory stimulation intact. We propose that a fundamental role of astrocyte Ca is to amplify functional hyperemia when neuronal activation is prolonged.
当增强的神经元活动信号提示增加局部脑血流 (CBF) 以满足区域能量需求时，就会发生功能性充血。星形细胞中的 Ca 升高可以驱动小动脉扩张以增加 CBF，但在体内功能性充血中星形细胞必要性的肯定证据是缺乏的。在清醒的小鼠中，我们发现功能性充血呈双峰模式，具有明显的早期和晚期成分，其中小动脉扩张随着感觉刺激的持续而进展。通过表达质膜 Ca ATP 酶（CalEx）在体内钳制星形细胞 Ca 信号会减少持续但不是短暂的感觉诱发的小动脉扩张。使用化学遗传学升高星形细胞游离 Ca 选择性增强持续充血。拮抗 NMDA 受体或环氧二十碳三烯酸的产生仅减少功能性充血的晚期成分，使感觉刺激引起的短暂 CBF 增加保持完整。我们提出，星形细胞 Ca 的一个基本作用是在神经元激活延长时放大功能性充血。
