LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia
Neuron. 2020-09-01; :
DOI: 10.1016/j.neuron.2020.08.030
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Henneberger C(1), Bard L(2), Panatier A(3), Reynolds JP(2), Kopach O(2), Medvedev:NI(4), Minge D(5), Herde MK(5), Anders S(5), Kraev I(4), Heller JP(2), Rama S(2), Zheng K(2), Jensen TP(2), Sanchez-Romero I(6), Jackson CJ(7), Janovjak H(8), Ottersen OP(9), Nagelhus EA(10), Oliet SHR(11), Stewart MG(12), Nägerl UV(13), Rusakov DA(14).
Author information:
(1)UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK; Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, 53127 Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), 53175 Bonn, Germany. Electronic address: .
(2)UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
(3)INSERM U1215, Neurocentre Magendie, 33000 Bordeaux, France; Université de Bordeaux, 33000 Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, 33000 Bordeaux, France.
(4)Life Sciences, The Open University, Milton Keynes MK7 6AA, UK.
(5)Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, 53127 Bonn, Germany.
(6)Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
(7)Research School of Chemistry, Australian National University, Acton, ACT 2601, Australia.
(8)Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria; EMBL Australia, Australian Regenerative Medicine Institute, Faculty of Medicine, Nursing and Health Science, Monash University, Melbourne, VIC 3800, Australia.
(9)Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway; Karolinska Institutet, 171 77 Stockholm, Sweden.
(10)Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
(11)INSERM U1215, Neurocentre Magendie, 33000 Bordeaux, France; Université de Bordeaux, 33000 Bordeaux, France.
(12)Life Sciences, The Open University, Milton Keynes MK7 6AA, UK. Electronic address: .
(13)Université de Bordeaux, 33000 Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, 33000 Bordeaux, France. Electronic address: .
(14)UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK. Electronic address: .
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.