Sonia Garel

Introduction
The general objective of the laboratory is to understand how the circuits of the anterior brain, which allow sensory perception, motor responses and cognition, are functionally implemented during development. These processes begin in the embryo, where intrinsic development programs coordinate the assembly of neurons through a complex choreography of neural migration and axonal navigation. However, these intrinsic programs can be disrupted by the maternal environment, as illustrated by the fact that prenatal inflammation is a risk for neurodevelopmental diseases, such as schizophrenia and autism spectrum disorders. Understanding how embryonic programs and maternal signals control the assembly of anterior brain circuitry is therefore essential not only to advance our understanding of brain morphogenesis, but also to establish a framework for evaluating the etiology of disease.

Projects and achievements

In order to do this, the laboratory examines how migration shapes the assembly of anterior brain circuits, how these circuits establish long-distance axonal connections, and how microglial cells, the resident macrophages of the brain that are activated by prenatal inflammation, contribute to these two processes. These issues are addressed using a combination of tools such as mouse molecular genetics, ex vivo culture systems, in vitro multi-protein patterning, and advanced intermittent imaging (time lapse), which allow the manipulation of structures, genes, and environmental factors.

Previous work in the laboratory has shown that brain “wiring” is based on a complex map of interactions between neurons but also with immune cells, microglia. Initial studies have demonstrated a role of migration in the construction of connectivity and raised the question of whether migration is itself regulated by this cabling. These studies also demonstrated the need to study all interactions, including those involving non-neuronal cells. Recent laboratory publications reveal that microglia constitute a general “entry point” into the embryonic brain for a wide variety of environmental factors, including the microbiome. Genetic or environmental defects in the microglia alter the neocortical wiring and its functioning, revealing how genetic immune deficiencies or external signals contribute to pathological brain morphogenesis.

Impact

Deciphering how transient interactions amongst neurons and with immune cells contribute to the emergence of functional circuits is essential for our comprehension of brain wiring and evolution. It also opens new avenues for understanding the role of the immune system and its activation in pathological conditions.