TY  - JOUR
AU  - Henneberger, Christian
AU  - Bard, Lucie
AU  - Panatier, Aude
AU  - Reynolds, James P
AU  - Kopach, Olga
AU  - Medvedev, Nikolay I
AU  - Minge, Daniel
AU  - Herde, Michel K
AU  - Anders, Stefanie
AU  - Kraev, Igor
AU  - Heller, Janosch P
AU  - Rama, Sylvain
AU  - Zheng, Kaiyu
AU  - Jensen, Thomas P
AU  - Sanchez-Romero, Inmaculada
AU  - Jackson, Colin J
AU  - Janovjak, Harald
AU  - Ottersen, Ole Petter
AU  - Nagelhus, Erlend Arnulf
AU  - Oliet, Stephane H R
AU  - Stewart, Michael G
AU  - Nägerl, U Valentin
AU  - Rusakov, Dmitri A
TI  - LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.
JO  - Neuron
VL  - 108
IS  - 5
SN  - 0896-6273
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2022-00941
SP  - 919 - 936.e11
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Astrocytes: metabolism
KW  - Astrocytes: ultrastructure
KW  - Female
KW  - Glutamic Acid: metabolism
KW  - Imaging, Three-Dimensional: methods
KW  - Long-Term Potentiation: physiology
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Mice, Transgenic
KW  - Organ Culture Techniques
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Rats, Wistar
KW  - Synapses: metabolism
KW  - Synapses: ultrastructure
KW  - Excitatory synapse (Other)
KW  - astrocyte plasticity (Other)
KW  - barrel cortex (Other)
KW  - glutamate sensor imaging (Other)
KW  - glutamate spillover (Other)
KW  - hippocampus (Other)
KW  - long-term potentiation (Other)
KW  - perisynaptic astroglial processes (Other)
KW  - super-resolution microscopy (Other)
KW  - whisker stimulation (Other)
KW  - Glutamic Acid (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32976770
C2  - pmc:PMC7736499
DO  - DOI:10.1016/j.neuron.2020.08.030
UR  - https://pub.dzne.de/record/164287
ER  -