Year: 2020
Type: article
Abstract: 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 Ca 2+ -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.
Source: Neuron
Authors: 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
Institutions: University of Bonn, German Center for Neurodegenerative Diseases, UCL Queen Square Institute of Neurology, University College London, Centre National de la Recherche Scientifique, Université de Bordeaux, Inserm, Neurocentre Magendie, Institut Interdisciplinaire de Neuroscience, The Open University, Institute of Science and Technology Austria, Australian National University, Australian Regenerative Medicine Institute, EMBL Australia, Monash University, University of Oslo, Karolinska Institutet
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,200
Funders: European Molecular Biology Organization, Wellcome Trust, University College London, European Commission, Human Frontier Science Program, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Bordeaux, LabEx BRAIN, Medical Research Council, European Research Council
Awards: G120131529, G177447034, G1893551499, G195628441, In the brain, at the level of a single synapse an individual astrocyte releases several gliotransmitters, G2052371694, Social media and sleep: ethical agendas in the digital age, G3636093897, G3757650242, G4277545659, G4555868579, G459516591, G509498957, G5188301940, G5263273319, G5665271876, G5959744682, Contribution of IP3Rs and endoplasmic reticulum to Ca2+ signalling in astrocytes, G6330196876, Co-agonist site of NMDA receptors: From synaptic dynamics to novel signalling mechanisms, G6803667113, Synaptic mechanisms of memory loss: novel cell adhesion molecules as therapeutic targets, G7240651115, Neural coding with the tripartite synapse., G7777338382, G8134629500, Principles of synapse-astrocyte networking in the brain
OpenAlex ID: W3087901293