Microglial Cells in the Human Brain: Distinct Motilities, Phenotypes, and Neuronal Interactions in Development and Epilepsy
Invited by Florian Fallegger, Dr Giampaolo Milior (PhD - Researcher - Molecular Imaging Center, Institut Jacob, Université Paris Saclay - CEA) will speak on Thursday March 6th. Meet at 3.00 PM - in the Institut de la Vision, Salle Lusseyran.
Abstract
Microglia, the resident macrophages of the brain, play a crucial role in immunity, repair, and plasticity within the central nervous system. They are essential for brain homeostasis and influence neuronal function throughout development, aging, and various physio-pathological states. Microglia exhibit diverse motility patterns that depend on their phenotype and are often triggered by purinergic signaling. In rodents, purinergic signaling is linked to changes in cell morphology, such as process extension toward tissue damage. However, little is known about the motility of living human microglia in ex vivo conditions, particularly in pathological contexts. We developed a reliable technique to stain live microglia in human acute ex vivo tissues and examined their motility in tissue slices from epileptic patients. Live imaging revealed unexpected purine-induced microglial behaviors, including membrane ruffling, process extension, and retraction, mediated by distinct P2Y receptor subtypes.
Further experiments suggest that these P2Y-dependent microglial motilities modulate neuronal activity in the developing human cortex and may contribute to childhood epilepsy onset. In particular, preliminary data revealed a unique spatial relationship between microglia, PV interneurons, and their synapses, consistent with phagocytic or synaptic pruning activities. Additionally, human microglia exhibited a P2Y12-specific modulation of neuronal activity, which may directly impact epilepsy onset. Studying living human microglia is thus critical to identifying differences from animal models and developing alternative therapeutic targets for epilepsy treatment.
About Giampaolo Milior
Giampaolo Milior holds a PhD in Neurophysiology and Clinical and Experimental Neurosciences, obtained in 2016 from La Sapienza University of Rome. His doctoral research investigated the role of microglial cells in brain development and depressive-like behaviors.
Following his PhD, he joined the Brain and Spine Institute (ICM) in Paris, where he contributed to pioneering research on a novel living model of the human brain, elucidating microglia's involvement in epilepsy onset. In 2019, he moved to the Collège de France, joining Dr. Nathalie Rouach’s laboratory to explore astrocytic functions in epilepsy through advanced imaging and electrophysiology techniques.
Recently appointed as a tenured researcher at the Molecular Imaging Research Center (CEA), he is establishing his own research group to investigate the gut microbiota–glia axis in human brain development . His current work focuses on refining a 3D ex vivo human brain model for targeted genetic manipulations of glial cells, aiming to develop innovative therapeutic strategies against developmental disorders and epilepsies.