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Valentin Nägerl et al in Neuron

Collaborative study with Christian Henneberger (Univ. of Bonn), Dmitri Rusakov (UCL) and Aude Panatier and Stéphane Oliet (Neurocentre Magendie).

Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this 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 localization reveal that LTP induction thus prompts spatial retreat of astroglial 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 a memory trace at one synapse could alter signal handling by multiple neighboring connections.

Nanoscale remodeling of astroglial processes after LTP increases spillover of synaptic glutamate
Nanoscale remodeling of astroglial processes after LTP increases spillover of synaptic glutamate

Article

LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia
Christian Henneberger*, Lucie Bard*, Aude Panatier*, James P. Reynolds*, Olga Kopach*, Nikolay I. Medvedev*, Daniel Minge*, Michel K. Herde, Stefanie Anders, Igor Kraev, Janosch P. Heller, Sylvain Rama, Kaiyu Zheng, Thomas P. Jensen, Inmaculada Sanchez-Romero, Colin J. Jackson, Harald Janovjak, Ole Petter Ottersen, Erlend Arnulf Nagelhus, Stephane H.R. Oliet, Michael G. Stewart, U. Valentin Nägerl, Dmitri A. Rusakov
Neuron ; September 24, 2020

* Co first authors

https://doi.org/10.1016/j.neuron.2020.08.030

Corresponding authors


25/09/20 // Category: Commented publications