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

Research output: Contribution to journalArticlepeer-review

131 Citations (Scopus)
144 Downloads (Pure)

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 languageEnglish
Pages (from-to)4552-4570
Number of pages19
JournalJournal of Neuroscience
Volume35
Issue number11
Early online date18 Mar 2015
DOIs
Publication statusPublished - 18 Mar 2015

Keywords

  • Chemokine
  • Chronic pain
  • Fractalkine
  • Microglia
  • Spinal cord
  • Synaptic plasticity

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