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警觉依赖的去甲肾上腺素能信号对小鼠小脑伯格曼胶质细胞的限制。

Constraints of vigilance-dependent noradrenergic signaling to mouse cerebellar Bergmann glia.

机构信息

Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

出版信息

Glia. 2023 Jun;71(6):1451-1465. doi: 10.1002/glia.24350. Epub 2023 Feb 15.

Abstract

Behavioral state plays an important role in determining astroglia Ca signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca elevations depend on their α -adrenergic receptors. With increasing availability and implementation of locomotion as behavioral parameter it becomes important to understand the constraints of noradrenergic signaling to astroglia. Here we evaluated the effect of speed, duration and interval of locomotion on Ca signals in Bergmann glia as well as cerebellar noradrenergic axon terminals. We found almost no dependence on locomotion speed, but following the initial Ca transient prolonged locomotion events revealed a steady-state Ca elevation. Comparison of time course and recovery of transient Bergmann glia and noradrenergic terminal Ca dynamics suggested that noradrenergic terminal Ca activity determines Bergmann glia Ca activation and does not require noradrenergic receptor desensitization to account for attenuation during prolonged locomotion. Further, analyzing the correlation among Ca dynamics within regions within the field of observation we found that coordinated activity among noradrenergic terminals accounts for fluctuations of steady-state Bergmann glia Ca activity. Together, our findings will help to better understand astroglia Ca dynamics during less controlled awake behavior and may guide the identification of behavioral contexts preferably dependent on astroglia Ca signaling.

摘要

行为状态在确定星形胶质细胞钙信号中起着重要作用。特别是,运动介导的警觉性升高已被发现会触发整个大脑中星形胶质细胞的去甲肾上腺素依赖性全细胞钙升高。对于小脑伯格曼胶质细胞,最近发现运动诱导的瞬时钙升高依赖于它们的α-肾上腺素能受体。随着运动作为行为参数的可用性和实施的增加,了解去甲肾上腺素能信号对星形胶质细胞的限制变得越来越重要。在这里,我们评估了运动速度、持续时间和间隔对伯格曼胶质细胞和小脑去甲肾上腺素能轴突末梢钙信号的影响。我们发现几乎没有运动速度的依赖性,但在初始钙瞬变之后,延长的运动事件揭示了稳态钙升高。瞬时伯格曼胶质细胞和去甲肾上腺素能末梢钙动力学的时程和恢复的比较表明,去甲肾上腺素能末梢钙活动决定了伯格曼胶质细胞钙的激活,并且不需要去甲肾上腺素能受体脱敏来解释在延长的运动过程中的衰减。此外,分析观察区域内钙动力学之间的相关性,我们发现去甲肾上腺素能末梢之间的协调活动解释了稳态伯格曼胶质细胞钙活动的波动。总之,我们的发现将有助于更好地理解在不受控制的清醒行为期间星形胶质细胞钙动力学,并可能指导识别更好地依赖星形胶质细胞钙信号的行为背景。

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