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小胶质细胞衍生的嘌呤通过P2X4和A1受体调节苔藓纤维突触传递和可塑性。

Microglia-derived purines modulate mossy fibre synaptic transmission and plasticity through P2X4 and A1 receptors.

作者信息

George Jimmy, Cunha Rodrigo A, Mulle Christophe, Amédée Thierry

机构信息

Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, Bordeaux, France.

CNC Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

出版信息

Eur J Neurosci. 2016 May;43(10):1366-78. doi: 10.1111/ejn.13191. Epub 2016 Mar 1.

DOI:10.1111/ejn.13191
PMID:27199162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5069607/
Abstract

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 plasticity.

摘要

近期数据表明，小胶质细胞作为驻留在大脑中的类巨噬细胞，在生理和病理生理条件下均能调节神经元活动，因此现在被认为是突触伙伴。在不同的神经调质中，由小胶质细胞产生和释放的嘌呤已成为介导小胶质细胞与突触之间相互作用的有潜力的候选物质。嘌呤的细胞效应是通过一大类腺苷和ATP受体（P2受体）介导的。这些受体存在于脑突触中，但它们是否能对小胶质细胞衍生的嘌呤作出反应以调节突触传递和可塑性尚不清楚。在这里，我们使用了一个简单的模型，即将免疫激活的小胶质细胞添加到小鼠海马切片中，以研究它们对海马苔藓纤维（MF）与CA3锥体神经元之间突触传递和可塑性的影响。MF-CA3突触表现出突出的突触前可塑性形式，参与记忆的编码和检索。我们证明，小胶质细胞衍生的ATP分别作用于突触前P2X4受体和在胞外ATP转化为腺苷后作用于腺苷A1受体，从而差异性地调节MF-CA3突触的突触传递和短期可塑性。我们还报告说，P2X4受体密集地位于齿状回-CA3回路的苔藓纤维束中。总之，这项研究揭示了小胶质细胞衍生的嘌呤与MF-CA3突触之间的相互作用，并突出了小胶质细胞作为突触前可塑性的有效调节因子的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/90175d4048ad/EJN-43-1366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/3f37cba41b7b/EJN-43-1366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/ac34870c2e13/EJN-43-1366-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/cd6d41c136b9/EJN-43-1366-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/90175d4048ad/EJN-43-1366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/3f37cba41b7b/EJN-43-1366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/ac34870c2e13/EJN-43-1366-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/14f291ec8d58/EJN-43-1366-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/ea3065174de4/EJN-43-1366-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b03/5069607/90175d4048ad/EJN-43-1366-g006.jpg

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