A spatial threshold for astrocyte calcium surge

Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which astrocyte calcium plays a crucial role. Synaptically evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e., calcium surge. Because a single astrocyte may contact ~100,000 synapses, the control of the intracellular calcium signal propagation may have relevant consequences on brain function. Yet, the properties governing the spatial dynamics of astrocyte calcium remains poorly defined. Imaging subcellular responses of cortical astrocytes to sensory stimulation in mice, we show that sensory-evoked astrocyte calcium responses originated and remained localized in domains of the astrocytic arborization, but eventually propagated to the entire cell if a spatial threshold of >23% of the arborization being activated was surpassed. Using Itpr2^-/- mice, we found that type-2 IP₃ receptors were necessary for the generation of astrocyte calcium surge. We finally show using in situ electrophysiological recordings that the spatial threshold of the astrocyte calcium signal consequently determined the gliotransmitter release. Present results reveal a fundamental property of astrocyte physiology, i.e., a spatial threshold for astrocyte calcium propagation, which depends on astrocyte intrinsic properties and governs astrocyte integration of local synaptic activity and subsequent neuromodulation.