European project to look at the wiring of the brain during growth

One of the great questions of neurobiology, how the brain is built up during embryonic development, could be resolved by a young French scientist in an award winning project organised by the European Science Foundation (ESF) and the European Heads of Research Councils (EuroHORCS).

Sonia Garel has won one of the prestigious EURYI Awards granted annually to young scientists, to pursue her ground breaking research into mammalian forebrain development. She will tackle a number of fundamental questions relating both to the wiring of the brain during growth, and how evolution drove forward the sophisticated neural circuitry associated with mammals.

Garel will focus on two key processes involved in development of neural circuitry in the forebrains of young mammals as they grow. One of these processes concerns the formation of connections between neurons, the nerve cells of the brain. These connections are needed to process sensory information, execute motor functions, and provide the network for cognitive abilities. They are made up of nerve fibres called axons, which conduct electrical impulses between neurons. The other key process involves migration of brain cells to their correct positions after their manufacture. As Garel noted, these two processes are coordinated in the development of the mammalian brain, and yet have until now been studied separately for the sake of simplicity. Garel and her colleagues have already broken new ground by demonstrating the link between axon formation, and migration of cells, within the brain.

“While axon guidance and cell migration have been usually studied as independent processes, our group has shown for the first time that they are elegantly coordinated to ensure the formation of a major long-range connection of the mammalian brain, the thalamocortical projection,” said Garel. The thalamocortical projection is one of the significant evolutionary developments of the forebrain, comprising bundles of axonal connections linking two key centres, the thalamus, which relays external sensory information, and the cerebral cortex, the most highly developed region comprising the so-called grey matter.

The thalamocortical projections, that first appeared in reptiles, have been remodelled in rodents and in primates, and are therefore of great interest in the study of neurological evolution. This phase of accelerated changes in connections correlates with an increase in cell migration in the brain. But there was a price to pay for this sophistication in the form of disorders associated with neurological dysfunctions, which particularly afflict humans. Garel hopes that her work will also advance understanding of some of these disorders, which can arise through defects both in the network of axonal connections and in the process of cell migration.

“Understanding how neural circuits are elaborated during mammalian forebrain development is essential to gain insights into its normal functioning and to make progress in our comprehension of neurological and psychiatric disorders,” said Garel. But malfunctions in cell migration can be just as harmful. “During development, cell migration is essential to control the positioning of cells in the brain, and cell migration defects have been associated with several neuropsychiatry diseases such as epilepsy, schizophrenia or bipolar disorders,” said Garel.

Garel will conduct her research in mice, aiming to improve understanding of how cell migration and axonal circuit development fit together. “We have showed that, in mice embryos, migrating cells act as dynamic guideposts to guide growing axons towards their final target in the brain,” said Garel. “Our study thus opens a novel perspective of the role of cell migration in the formation of brain connections during normal and pathological development.”