Local Resting Ca²⁺ Controls the Scale of Astroglial Ca²⁺ Signals

Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca²⁺ signals, but what controls their amplitude and waveform is poorly understood. Here, we employ time-resolved two-photon excitation fluorescence imaging in acute hippocampal slices and in cortex in vivo to find that resting [Ca²⁺] predicts the scale (amplitude) and the maximum (peak) of astroglial Ca²⁺ elevations. We bidirectionally manipulate resting [Ca²⁺] by uncaging intracellular Ca²⁺ or Ca²⁺ buffers and use ratiometric imaging of a genetically encoded Ca²⁺ indicator to establish that alterations in resting [Ca²⁺] change co-directionally the peak level and anti-directionally the amplitude of local Ca²⁺ transients. This relationship holds for spontaneous and for induced (for instance by locomotion) Ca²⁺ signals. Our findings uncover a basic generic rule of Ca²⁺ signal formation in astrocytes, thus also associating the resting Ca²⁺ level with the physiological "excitability" state of astroglia.