Henneberger, C;
Bard, L;
Panatier, A;
Reynolds, JP;
Kopach, O;
Medvedev, NI;
Minge, D;
... Rusakov, DA; + view all
(2020)
LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.
Neuron
10.1016/j.neuron.2020.08.030.
(In press).
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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 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.
| Type: | Article |
|---|---|
| Title: | LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2020.08.030 |
| Publisher version: | http://dx.doi.org/10.1016/j.neuron.2020.08.030 |
| Language: | English |
| Additional information: | © 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Excitatory synapse, long-term potentiation, glutamate spillover, perisynaptic astroglial processes, astrocyte plasticity, glutamate sensor imaging, super-resolution microscopy, hippocampus, whisker stimulation, barrel cortex |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10110950 |
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