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

警觉依赖性去甲肾上腺素能信号传导对小鼠小脑伯格曼胶质细胞的限制

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Abstract

Behavioral state plays an important role in determining astroglia Ca(2+) signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca(2+) elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca(2+) elevations depend on their α(1A) -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(2+) signals in Bergmann glia as well as cerebellar noradrenergic axon terminals. We found almost no dependence on locomotion speed, but following the initial Ca(2+) transient prolonged locomotion events revealed a steady-state Ca(2+) elevation. Comparison of time course and recovery of transient Bergmann glia and noradrenergic terminal Ca(2+) dynamics suggested that noradrenergic terminal Ca(2+) activity determines Bergmann glia Ca(2+) activation and does not require noradrenergic receptor desensitization to account for attenuation during prolonged locomotion. Further, analyzing the correlation among Ca(2+) 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(2+) activity. Together, our findings will help to better understand astroglia Ca(2+) dynamics during less controlled awake behavior and may guide the identification of behavioral contexts preferably dependent on astroglia Ca(2+) signaling.

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