Selective activation of microglia facilitates synaptic strength

Anna K. Clark; Doris Gruber-Schoffnegger; Ruth Drdla-Schutting; Katharina J. Gerhold; Marzia Malcangio; Jürgen Sandkühler

doi:10.1523/JNEUROSCI.2061-14.2015

Selective activation of microglia facilitates synaptic strength

Anna K. Clark, Doris Gruber-Schoffnegger, Ruth Drdla-Schutting, Katharina J. Gerhold, Marzia Malcangio, Jürgen Sandkühler^*

^*Corresponding author for this work

Medical University of Vienna

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

143 Citations (Scopus)

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Abstract

Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1_ from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptictransmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.

Original language	English
Pages (from-to)	4552-4570
Number of pages	19
Journal	Journal of Neuroscience
Volume	35
Issue number	11
Early online date	18 Mar 2015
DOIs	https://doi.org/10.1523/JNEUROSCI.2061-14.2015
Publication status	Published - 18 Mar 2015

Keywords

Chemokine
Chronic pain
Fractalkine
Microglia
Spinal cord
Synaptic plasticity

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Selective activation of microglia_CLARK_Published18March2015_GOLD VoR (CC-BY)Final published version, 6.18 MBLicence: CC BY

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title = "Selective activation of microglia facilitates synaptic strength",

abstract = "Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1_ from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptictransmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.",

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AU - Gerhold, Katharina J.

AU - Malcangio, Marzia

AU - Sandkühler, Jürgen

N1 - Authors grant JNeurosci a license to publish their work and copyright remains with the author. For articles published after 2014, the Society for Neuroscience (SfN) retains an exclusive license to publish the article for 6 months; after 6 months, the work becomes available to the public to copy, distribute, or display under the terms of the Creative Commons Attribution 4.0 International License (CC-BY). This license allows data and text mining, use of figures in presentations, and posting the article online, provided that the original article is credited. Material published from 2010 to 2014 is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (CC-BY-NC-SA). SfN holds copyright for material published before 2010. Authors retain copyright for all material published in JNeurosci.

PY - 2015/3/18

Y1 - 2015/3/18

N2 - Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1_ from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptictransmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.

AB - Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1_ from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptictransmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.

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VL - 35

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JO - Journal of Neuroscience

JF - Journal of Neuroscience

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ER -

Selective activation of microglia facilitates synaptic strength

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