PT  - JOURNAL ARTICLE
AU  - Christian Henneberger
AU  - Lucie Bard
AU  - Aude Panatier
AU  - James P. Reynolds
AU  - Olga Kopach
AU  - Nikolay I. Medvedev
AU  - Daniel Minge
AU  - Michel K. Herde
AU  - Stefanie Anders
AU  - Igor Kraev
AU  - Janosch P. Heller
AU  - Sylvain Rama
AU  - Kaiyu Zheng
AU  - Thomas P. Jensen
AU  - Inmaculada Sanchez-Romero
AU  - Colin Jackson
AU  - Harald Janovjak
AU  - Ole Petter Ottersen
AU  - Erlend Arnulf Nagelhus
AU  - Stephane H.R. Oliet
AU  - Michael G. Stewart
AU  - U. Valentin Nägerl
AU  - Dmitri A. Rusakov
TI  - LTP induction boosts glutamate spillover by driving withdrawal of astroglia
AID  - 10.1101/349233
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 349233
4099  - http://biorxiv.org/content/early/2020/02/19/349233.short
4100  - http://biorxiv.org/content/early/2020/02/19/349233.full
AB  - 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.