Karine Loulier Tracks the Cells of the Cerebral Cortex

At the Institute for Neurosciences of Montpellier, Karine Loulier is studying the development of the cerebral cortex. The researcher is using a sophisticated fluorescent labeling technique in vivo in mice to track what happens to cells from the embryonic stage through to adulthood. In so doing, she hopes to learn more about cell diversity and how the balance is established among the various cortex cell types. She also wishes to identify abnormalities in this development which could be responsible for psychiatric disorders.

Karine Loulier is attempting to unlock the mysteries of the cerebral cortex. She not only wants to find out how it develops during embryogenesis, but also whether psychiatric disorders that occur in adolescence or adulthood are linked to abnormalities of this early development. For this, she recently put together her own team at the Institute for Neurosciences of Montpellier (INM), thanks to the ATIP-Avenir program. This was in September of last year, following an impeccable début in the neurosciences: a doctorate from Paris 11, two postdocs in the US and France and her recruitment as an Inserm researcher.

Over the course of her research, she has gathered and incorporated new techniques in the study of brain development. But it was during her second postdoc that she found her calling – in Jean Livet’s team at the Institut de la Vision. Livet is testing new labeling techniques, to simultaneously track the outcomes of various neuron populations and study their connectivity. A technique which Loulier familiarized herself with and developed. "It makes it possible to separately label small cell groups with distinct color codes, in vivo in mice, to monitor the outcome of each group over time", she explains. As such she was able to acquire solid expertise in the field before being recruited by Inserm for a researcher position in the same laboratory, in 2012.

Des neurones en couleurs – report and interview – 6 min 26 – video taken from the series Des idées plein la tech' (2011)

Psychiatric disorders in the line of sight

She then studied brain development in mice. "A group of stem cells is at the origin of many cells of the cortex and its networks: neurons, astrocytes and oligodendrocytes, but also stem cells that persist into adulthood. However, we still know practically nothing about how that comes about. Does a subgroup of stem cells give rise to only one cell type or do they undergo multiple changes during development to produce neurons followed by glial cells, for example? Anyway, what we are observing is that the mature cells of the cortex are a lot more complex than we thought. For example, the astrocytes, a glial cell subtype long suspected to serve only as support to the neurons, are highly plastic and their generation coincides with the start of the maturation of the cortical neuron network", illustrates Loulier. A huge undertaking, then. And the researcher wanted to go beyond the descriptive aspect: she wanted to use these combinatorial labeling techniques to correlate brain development abnormalities with psychiatric disorders. To do this, she set up a new project and submitted it to the ATIP-Avenir program, an initiative which allows young researchers to form their own teams.

Atip-Avenir opens all the doors

Her application was validated by a committee of experts in the neurosciences from France and other countries, enabling her to benefit from 60,000 euros per year for three years for her experiments, and to hire a postdoc for two years. "The ATIP-Avenir program opens all the doors, thanks to a solid project validated by a committee of international experts and a certain financial independence". She chose to set up at the INM which "encourages fundamental research while facilitating translational approaches, and which has a cutting-edge imaging platform and a first-rate animal facility". The INM is also contributing to the project by funding a technical assistant.

Now set up at the INM, Loulier is using her colored markers to study early brain development in mouse models of psychiatric disorders such as schizophrenia. She will also trigger cell imbalances during corticogenesis to observe the effects on behavior. Finally, she will test molecules to observe the effect on cerebral cortex development. In time, she hopes to identify the origin of certain psychiatric disorders and discover the factors linked to the developmental abnormalities thought to be responsible for them.

Karine Loulier is leader of the ATIP-Avenir team Corticogenesis: diversity and plasticity of neural stem cells during brain development, in healthy and pathological settings at the Institute for Neurosciences of Montpellier (INM, unit 1051 Inserm/Université de Montpellier).