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

doi:10.1016/j.neuron.2020.08.030

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. OlietMichael G. Stewart^*, U. Valentin Nägerl^*, Dmitri A. Rusakov^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

171 Citations (SciVal)

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.

Original language	English
Pages (from-to)	919-936.e11
Journal	Neuron
Volume	108
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2020.08.030
Publication status	Published - 9 Dec 2020

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Henneberger, C., Bard, L., Panatier, A., Reynolds, J. P., Kopach, O., Medvedev, N. I., Minge, D., Herde, M. K., Anders, S., Kraev, I., Heller, J. P., Rama, S., Zheng, K., Jensen, T. P., Sanchez-Romero, I., Jackson, C. J., Janovjak, H., Ottersen, O. P., Nagelhus, E. A., ... Rusakov, D. A. (2020). LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia. Neuron, 108(5), 919-936.e11. https://doi.org/10.1016/j.neuron.2020.08.030

@article{08b6d1fde3084dde97517f3cb2b298ae,

title = "LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia",

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.",

keywords = "Excitatory synapse, astrocyte plasticity, barrel cortex, glutamate sensor imaging, glutamate spillover, hippocampus, long-term potentiation, perisynaptic astroglial processes, super-resolution microscopy, whisker stimulation",

author = "Christian Henneberger and Lucie Bard and Aude Panatier and Reynolds, \{James P.\} and Olga Kopach and Medvedev, \{Nikolay I.\} and Daniel Minge and Herde, \{Michel K.\} and Stefanie Anders and Igor Kraev and Heller, \{Janosch P.\} and Sylvain Rama and Kaiyu Zheng and Jensen, \{Thomas P.\} and Inmaculada Sanchez-Romero and Jackson, \{Colin J.\} and Harald Janovjak and Ottersen, \{Ole Petter\} and Nagelhus, \{Erlend Arnulf\} and Oliet, \{Stephane H.R.\} and Stewart, \{Michael G.\} and N{\"a}gerl, \{U. Valentin\} and Rusakov, \{Dmitri A.\}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = dec,

day = "9",

doi = "10.1016/j.neuron.2020.08.030",

language = "English",

volume = "108",

pages = "919--936.e11",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "5",

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Henneberger, C, Bard, L, Panatier, A, Reynolds, JP, Kopach, O, Medvedev, NI, Minge, D, Herde, MK, Anders, S, Kraev, I, Heller, JP, Rama, S, Zheng, K, Jensen, TP, Sanchez-Romero, I, Jackson, CJ, Janovjak, H, Ottersen, OP, Nagelhus, EA, Oliet, SHR, Stewart, MG, Nägerl, UV & Rusakov, DA 2020, 'LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia', Neuron, vol. 108, no. 5, pp. 919-936.e11. https://doi.org/10.1016/j.neuron.2020.08.030

TY - JOUR

T1 - LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia

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.

PY - 2020/12/9

Y1 - 2020/12/9

N2 - 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.

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 - Excitatory synapse

KW - astrocyte plasticity

KW - barrel cortex

KW - glutamate sensor imaging

KW - glutamate spillover

KW - hippocampus

KW - long-term potentiation

KW - perisynaptic astroglial processes

KW - super-resolution microscopy

KW - whisker stimulation

UR - http://www.scopus.com/inward/record.url?scp=85092227249&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2020.08.030

DO - 10.1016/j.neuron.2020.08.030

M3 - Article

SN - 0896-6273

VL - 108

SP - 919-936.e11

JO - Neuron

JF - Neuron

IS - 5

ER -

LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia

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