LTP induction boosts glutamate spillover by driving withdrawal of astroglia
James P. Reynolds,
Nikolay I. Medvedev,
Michel K. Herde,
Janosch P. Heller,
Thomas P. Jensen,
Ole Petter Ottersen,
Erlend Arnulf Nagelhus,
Stephane H.R. Oliet,
Michael G. Stewart,
U. Valentin Nägerl,
Dmitri A. Rusakov
Posted 17 Jun 2018
bioRxiv DOI: 10.1101/349233
Posted 17 Jun 2018
Extrasynaptic actions of glutamate are limited by high-affinity transporters on perisynaptic astroglial processes (PAPs), which helps to maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodelling, but how this remodelling affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here we used advanced imaging methods, in situ and in vivo , to find that a classical synaptic memory mechanism, long-term potentiation (LTP), triggers withdrawal of PAPs from potentiated synapses. Optical glutamate sensors combined with patch-clamp and 3D molecular localisation reveal that LTP induction thus prompts a spatial retreat of glial glutamate transporters, boosting glutamate spillover and NMDA receptor-mediated inter-synaptic cross-talk. The LTP-triggered PAP withdrawal involves NKCC1 transporters and the actin-controlling protein cofilin but does not depend on major Ca2+-dependent cascades in astrocytes. We have therefore uncovered a mechanism by which synaptic potentiation could alter signal handling by multiple nearby connections.
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