Highlights d Induction of synaptic LTP prompts withdrawal of perisynaptic astroglia d The underlying mechanisms involve NKCC1 transporter and cofilin d Reduced synaptic astroglial coverage boosts extrasynaptic glutamate escape d LTP induction thus enhances NMDAR-dependent intersynaptic cross-talk

SummaryMaintaining low intracellular calcium is essential to the functioning of brain cells, yet the phenomenology and mechanisms involved remain an enigma. We have advanced a two-photon excitation time-resolved imaging technique, which exploits high sensitivity of the OGB-1 fluorescence lifetime to nanomolar Ca2+ concentration ([Ca2+]) and enables a high data acquisition rate in situ. The [Ca2+] readout is not affected by dye concentration, light scattering, photobleaching, micro-viscosity, temperature, or the main known concomitants of cellular activity. In quiescent tissue, standard whole-cell configuration has little effect on resting [Ca2+] inside neuronal dendrites or inside astroglia dye-filled via gap junctions. Mapping basal [Ca2+] in neurons and astrocytes with submicron resolution unveils heterogeneous concentration landscapes that depend on age and preceding activity. The rich information content represented by such landscapes in acute slices and in vivo promises to unveil the hitherto unexplored, potentially fundamental aspects of brain cell physiology.Video Abstract

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