PhD: The role of microglial cells in the development of neuronal circuits
Defended: December 7, 2016
Microglial cells, the resident macrophages of the central nervous system, were mainly studied for their role in pathological conditions, but they recently appeared to be involved in synaptic development and circuits formation during postnatal period. During this critical period, microglial cells colonize the central nervous system and interact with other cell types, including neurons.
A specific way of communication between neurons and microglia involves neuronal released fractalkine (CX3CL1) and its specific microglial receptor CX3CR1. CX3CR1 KO mice contributed to unclose microglial role during development. Indeed, CX3CR1 ablation alters microglia distribution in the brain, and it affects glutamatergic transmission and synapse maturation. However, these effects seem to be transient and brain region specific and their mechanisms are poorly understood.
Furthermore, some effects observed in juvenile or adult mice may have origin during development, when neuronal connections are established. GABA plays a fundamental role in this process since it is excitatory. The influence of neuron-microglia interaction on neuronal activity in the hippocampus during this period is poorly understood. In particular, nothing is known on GABAergic activity, known to be synaptogenic during this period.
My PhD project aimed at investigating how the signaling fractalkine pathway impacts microglial colonization of the hippocampus and neuronal activity during the first two postnatal weeks. Our results indicate that in CX3XR1KO mice there is a reduction in the density of microglial cells at P7-P9 in the CA3 hippocampal area, accompanied at P7 by a significant reduction of frequency of Giant Depolarizing Potentials (GDPs), a network activity involved in hippocampal synapse formation and maturation. Furthermore, despite no overall difference in glutamatergic or GABAergic synaptic activity, GABAergic events display a subpopulation of larger events, and the kinetics was slightly faster. Thus, the disruption of the specific neuronal-microglia signaling pathway on one hand impacts the microglia colonization of the hippocampus and on the other hands affects specifically neuronal network activity during a time window critical for the establishment of neuronal connections. Key words: microglia, Hippocampus, postnatal development, GDPs, network, GABA
Mots clés : microglie, Hippocampe, développement postnatal, GDPs, réseau, GABA
Publication Bertot, C., Groc, L., Avignone, E. The neuron-microglia signaling tunes neuronal network, but not synaptic, activity in the neonate hippocampus (in preparation).
PU, Université de Bordeaux
DR, Aix-Marseille Université Rapporteur
DR, Université Paris Descartes Rapporteur
Université de Bordeaux
Université de Bordeaux
Directeur de thèse