Local Resting Ca(2+) Controls the Scale of Astroglial Ca(2+) Signals

Astroglia regulate neurovascular coupling while engaging in signal exchange with neurons. The underlying cellular machinery is thought to rely on astrocytic Ca(2+) 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 [Ca(2+)] predicts the scale (amplitude) and the maximum (peak) of astroglial Ca(2+) elevations. We bidirectionally manipulate resting [Ca(2+)] by uncaging intracellular Ca(2+) or Ca(2+) buffers and use ratiometric imaging of a genetically encoded Ca(2+) indicator to establish that alterations in resting [Ca(2+)] change co-directionally the peak level and anti-directionally the amplitude of local Ca(2+) transients. This relationship holds for spontaneous and for induced (for instance by locomotion) Ca(2+) signals. Our findings uncover a basic generic rule of Ca(2+) signal formation in astrocytes, thus also associating the resting Ca(2+) level with the physiological “excitability” state of astroglia.