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Inhibitory synapses regulation by glia and inflammation

Head of project : Alain Bessis

Microglia are non-neuronal cells of the nervous tissue. They display strong phagocytic activity, and the microglial functions that have been best described are related to their ability eliminate dead cells, cellular debris etc. However, it is more and more accepted that microglia are more than “housekeeping cells” but rather are full-time partners of neuronal function.

Thus, microglia are extremely ramified and dynamic cells that permanently extend and retract their processes to scan the brain and rapidly react to the modification of the environment. We and others have shown that microglia are able to induce the physiological death of developing neurons and that they participate to the growth of axons during development.

We showed that microglia are genuine partners of excitatory neurotransmission and we are now investigating how microglia can tune the synaptic function by controlling the behaviour of neurotransmitter receptors. To this aim, we are using up-to-date imaging approaches to monitor receptors dynamic and microglia-synapses interactions.

Participants : A. Bessis, I. Vaccari, Y. Cantaut-Belarif, S. Colasse

Cantaut-Belarif Y, M. Antri, R. Pizzarelli, S. Colasse, I. Vaccari, S. Soares, M. Renner, R. Dallel, A. Triller, and A. Bessis (2017) Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord. The Journal of Cell Biology. jcb.201607048. doi:10.1083/jcb.201607048

Béchade C, S. Colasse, M. Diana, M. Rouault, and A. Bessis (2014) NOS2 expression is restricted to neurons in the healthy brain but is triggered in microglia upon inflammation. Glia. 62:956–63. doi:10.1002/glia.22652

Squarzoni P, G. Oller, G. Hoeffel, L. Pont-Lezica, P. Rostaing, D. Low, A. Bessis, F. Ginhoux, and S. Garel (2014) Microglia modulate wiring of the embryonic forebrain. CellReports. 8:1271-9. doi:10.1016/j.celrep. 2014.07.042

Pont-Lezica L, W. Beumer, S. Colasse, H. Drexhage, M. Versnel, and A. Bessis (2014) Microglia shape corpus callosum axon tract fasciculation : functional impact of prenatal inflammation. Eur J Neurosci. 39:1551–7. doi:10.1111/ejn.12508

Pascual O, S.B. Achour, P. Rostaing, A. Triller, and A. Bessis (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc Natl Acad Sci USA. 109:E197–205. doi:10.1073/ pnas.1111098109