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J Neurosci. 2015 Mar 18;35(11):4552-70. doi: 10.1523/JNEUROSCI.2061-14.2015.

Selective activation of microglia facilitates synaptic strength.

Author information

1
Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria, and Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, United Kingdom.
2
Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria, and.
3
Wolfson Centre for Age Related Diseases, King's College London, London SE1 1UL, United Kingdom.
4
Department of Neurophysiology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria, and juergen.sandkuehler@meduniwien.ac.at.

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-1β 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 synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.

KEYWORDS:

chemokine; chronic pain; fractalkine; microglia; spinal cord; synaptic plasticity

PMID:
25788673
PMCID:
PMC4363384
DOI:
10.1523/JNEUROSCI.2061-14.2015
[Indexed for MEDLINE]
Free PMC Article

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