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

Abstract

Behavioral state plays an important role in determining astroglia Ca²⁺ signaling. In particular, locomotion-mediated elevated vigilance has been found to trigger norepinephrine-dependent whole cell Ca²⁺ elevations in astroglia throughout the brain. For cerebellar Bergmann glia it has recently been found that locomotion-induced transient Ca²⁺ 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 Ca²⁺ signals in Bergmann glia as well as cerebellar noradrenergic axon terminals. We found almost no dependence on locomotion speed, but following the initial Ca²⁺ transient prolonged locomotion events revealed a steady-state Ca²⁺ elevation. Comparison of time course and recovery of transient Bergmann glia and noradrenergic terminal Ca²⁺ dynamics suggested that noradrenergic terminal Ca²⁺ activity determines Bergmann glia Ca²⁺ activation and does not require noradrenergic receptor desensitization to account for attenuation during prolonged locomotion. Further, analyzing the correlation among Ca²⁺ dynamics within regions within the field of observation we found that coordinated activity among noradrenergic terminals accounts for fluctuations of steady-state Bergmann glia Ca²⁺ activity. Together, our findings will help to better understand astroglia Ca²⁺ dynamics during less controlled awake behavior and may guide the identification of behavioral contexts preferably dependent on astroglia Ca²⁺ signaling.

Keywords: Bergmann glia; arousal; astroglia; calcium signaling; cerebellum; locomotion; locus coeruleus; norepinephrine; vigilance.