Astroglia withdraw from potentiated synapses boosting inter-synaptic cross-talk

Astroglia generate molecular signals essential for synaptic plasticity while constraining extrasynaptic escape of the excitatory neurotransmitter glutamate. The degree of glutamate escape impacts on signal integration in many neural circuits, ultimately influencing brain cognitive function. Whether synaptic plasticity prompts perisynaptic astroglial changes that might affect extrasynaptic glutamate actions remains poorly understood. We monitored perisynaptic astroglia using a battery of light diffraction-insensitive microscopy methods and found that the induction of a classical synaptic memory paradigm, long-term potentiation (LTP), in situ and in vivo, triggers sub-microscopic astroglial withdrawal from potentiated synapses. Optical glutamate sensors combined with single-cell electrophysiology revealed that LTP-triggered withdrawal of perisynaptic astroglia facilitates extrasynaptic glutamate escape boosting NMDA receptor-mediated cross-talk among neighbouring synapses. This phenomenon depends on astroglial NKCC1 transporters and successful LTP induction whereas the latter does not require astrocyte morphogenesis. Thus, induction of synaptic plasticity also engages a cellular astroglial mechanism regulating glutamate signaling landscape in synaptic circuits of the brain.