Glial Interactions in Cortical Circuits During Human Brain Development: Role in Childhood Epilepsies
Since my PhD in Neurophysiology, I have developed a particular interest in studying glia-neuron interactions in both physiological and pathological conditions of the brain. Using electrophysiology and live imaging techniques, I have uncovered novel mechanisms by which microglia and astrocytes modulate neuronal activity, directly influencing brain excitability. During my PhD, I worked on a project investigating microglia-neuron interactions in mouse models of stress-induced depression (Milior et al., 2016). I was also an integral part of the team that first identified "dark microglia," a microglial state highly prevalent under exposure to various risk factors (e.g., stress, aging) and disease conditions (Bisht et al., 2016).
In 2016, I joined the laboratory of Prof. Richard Miles at the ICM, Pitié-Salpêtrière, as a postdoctoral researcher. Thanks to several collaborations with neurosurgeons and clinicians, I had the opportunity to analyze brain tissues from patients suffering from epilepsy, focusing in particular on the differential effects of microglial activation during seizures. In the Miles group, I investigated the immune consequences of epileptic seizures and characterized the unique motility responses of human microglia (Milior et al., 2020; Morin-Brureau et al., 2018). This pioneering work included the refinement of ex vivo human brain models, such as long-term organotypic slice cultures, enabling live imaging, electrophysiology, and viral manipulations (Le Duigou et al., 2018).
Since 2019, I have continued my research on the human brain as a postdoctoral fellow in the laboratory of Prof. Nathalie Rouach at the CIRB, Collège de France. I have remained focused on investigating dynamic interactions between glial cells and neurons. In human peritumoral brain tissues, I explored the role of astrocytic IP3R receptors as potential markers for astrocytoma invasion and epilepsy. I studied how IP3R-mediated signaling in astrocytes and microglia impacts tumor progression and the incidence of peri-tumoral epileptic activity.
I was recently recruited as a tenured researcher, and for the coming years, I am proposing an innovative research project focused on the interplay between microglia and astrocytes during human brain development. My research team will further explore how altered glial interactions contribute to malformations of human cortical development and childhood epilepsies.
The future research team will investigate how glial cells control key neurodevelopmental processes in the human brain and how their dysfunction can lead to neurodevelopmental disorders. This project introduces a novel set of questions and experimental paradigms, leveraging advanced techniques and human tissue preparations to uncover mechanisms specific to human brain physiology and pathology.
