Activity-dependent remodelling of synaptic microenvironment

Memory formation is thought to involve structural remodelling of synaptic connections. How this engages the perisynaptic microenvironment inhabited by astroglia, is poorly understood. We combine single-cell electrophysiology with two-photon excitation microscopy, photolytic uncaging, super-resolution techniques, and correlational 3D electron microscopy, to monitor fine astroglial morphology during the induction of synaptic long-term potentiation (LTP). We find that LTP induction, either in multiple or in individual identified synapses, triggers nanoscopic withdrawal of perisynaptic astroglial processes. The reduction in synaptic astroglial coverage boosts extra-synaptic glutamate escape thus facilitating NMDA receptor-mediated cross-talk among neighbouring synapses. Thus, LTP induction can alter the spatial profile of neurotransmitter actions, hence signal integration rules, in the extracellular proximity of potentiated synapses. The underlying cellular mechanisms do not depend on major cascades of astroglial Ca²⁺-dependent signalling but require the ion exchanger NCCK1 and involve the actin-controlling cofilin signalling.