A spatial threshold for astrocyte calcium surge

• DOI: 10.7554/elife.90046.2
• Publication Date: 2024-11-18T16:25:13Z
• Authors: Justin Lines; Andres Baraibar; Carmen Nanclares; Eduardo D Martín; Juan Aguilar; Paulo Kofuji; Marta Navarrete; Alfonso Araque
• Keywords: 0301 basic medicine; 0303 health sciences; Gliotransmitter release; calcium; QH301-705.5; Science; Q; R; Spatial threshold; integration; Cell Biology; Synaptic activity; synaptic integration; Calcium surge; astrocyte; Astrocyte, synaptic integration, astrocyte integration, calcium surge, calcium imaging, 26 fluorescence microscopy.; Medicine; Biology (General); Astrocyte; Intracellular calcium

Abstract Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which the astrocyte calcium signal 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. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because a single astrocyte may contact ∼100,000 synapses, the control of the intracellular calcium signal propagation may have relevant consequences on brain function by regulating the spatial range of astrocyte neuromodulation of synapses. Yet, the properties governing the spatial dynamics of the astrocyte calcium signal 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 transgenic IP3R2-/- mice, we found that type-2 IP3 receptors were necessary for the generation of the 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 calcium physiology, i.e., a spatial threshold for the astrocyte intracellular calcium signal propagation, which depends on astrocyte intrinsic properties and governs the astrocyte integration of local synaptic activity and the subsequent neuromodulation.