Microglia-derived purines modulate mossy fibre synaptic transmission and plasticity through P2X4 and A1 receptors.
Eur J Neurosci. 2016-03-01; 43(10): 1366-1378
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1. Eur J Neurosci. 2016 May;43(10):1366-78. doi: 10.1111/ejn.13191. Epub 2016 Mar 1.
Microglia-derived purines modulate mossy fibre synaptic transmission and
plasticity through P2X4 and A1 receptors.
George J(1)(2)(3), Cunha RA(2)(3), Mulle C(1), Amédée T(1)(4).
(1)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of
Bordeaux, Bordeaux, France.
(2)CNC Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra,
(3)Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
(4)IINS, UMR 5297 CNRS – Université de Bordeaux, Bordeaux Cedex, France.
Recent data have provided evidence that microglia, the brain-resident
macrophage-like cells, modulate neuronal activity in both physiological and
pathophysiological conditions, and microglia are therefore now recognized as
synaptic partners. Among different neuromodulators, purines, which are produced
and released by microglia, have emerged as promising candidates to mediate
interactions between microglia and synapses. The cellular effects of purines are
mediated through a large family of receptors for adenosine and for ATP (P2
receptors). These receptors are present at brain synapses, but it is unknown
whether they can respond to microglia-derived purines to modulate synaptic
transmission and plasticity. Here, we used a simple model of adding
immune-challenged microglia to mouse hippocampal slices to investigate their
impact on synaptic transmission and plasticity at hippocampal mossy fibre (MF)
synapses onto CA3 pyramidal neurons. MF-CA3 synapses show prominent forms of
presynaptic plasticity that are involved in the encoding and retrieval of memory.
We demonstrate that microglia-derived ATP differentially modulates synaptic
transmission and short-term plasticity at MF-CA3 synapses by acting,
respectively, on presynaptic P2X4 receptors and on adenosine A1 receptors after
conversion of extracellular ATP to adenosine. We also report that P2X4 receptors
are densely located in the mossy fibre tract in the dentate gyrus-CA3 circuitry.
In conclusion, this study reveals an interplay between microglia-derived purines
and MF-CA3 synapses, and highlights microglia as potent modulators of presynaptic
© 2016 The Authors. European Journal of Neuroscience published by Federation of
European Neuroscience Societies and John Wiley & Sons Ltd.
PMID: 27199162 [Indexed for MEDLINE]