What field of research are you involved in ?
I'm doing a PhD in neurobiology, studying postnatal brain development. I'm specifically interested in one cell type, astrocytes, which are part of what are known as glial cells. Glial cells are less well known than neuronal cells, but just as essential. They are found throughout the nervous system, both central (brain and spinal cord) and peripheral.
What are glial cells, and why are they important ?
There are several types of glial cell, with different forms and functions. In the brain, we find :
1°) oligodendrocytes, which are responsible for producing a specific sheath that facilitates the passage of nerve messages between neurons ;
2°) microglial cells, the brain's immune cells. They defend the brain against pathogens and are activated in the event of lesions ;
3°) astrocytes, which lie between blood vessels and neurons, and have a variety of functions : in particular, they provide nutritive support to neurons and are capable of dialoguing with them at synapses, points of communication between two neurons.
Astrocytes are the subject of my research.
Over the last thirty years or so, we have come to realize that astrocytes play a vital role in the brain, and we still have a lot to learn about them. For example, it is thought that their dysfunction may be involved in neurodegenerative diseases such as Alzheimer's.
How do you go about your day-to-day work ?
I don't have a work routine. It all depends on my objectives and experimental results. There are periods when I'm just going to analyze my results and put them into shape, and other periods devoted to experiments.
My research team is quite large : Nathalie Rouach, the head of the laboratory, is also my thesis co-director, along with Glenn Dallérac, a researcher at the University of Paris-Saclay. I also work with Jérôme Ribot, a research engineer in Nathalie Rouach's team, and the other members of the team, with whom I also have strong scientific and friendly interactions.
The great thing about the Collège de France is that we have all the necessary technical tools at our disposal, such as an imaging platform with very powerful microscopes, and excellent data analysis tools. And it's a beautiful site right in the heart of Paris !
What is your background ?
I did my first year of a bachelor's degree in biology, geosciences and chemistry at Pierre-et-Marie-Curie University (now Sorbonne University). I was interested in science in general, and at first I didn't know which scientific discipline to choose. In my second year, I specialized in biology, then in my third year I took an option called " Glial cells and pathologies of the nervous system ". In the classical biology curriculum, very little is said about glial cells, which I thought was a pity, because I learned so much thanks to this option. As a result, I did a Master's internship at 1 which focused on the interactions between glial cells and neurons, a happy experience which confirmed my decision to continue in this field. I then specialized in neuroscience. My Master's internship at 2, and then my current thesis, took place in Nathalie Rouach's laboratory.
When is the brain most sensitive to stimulation ?
During the period known as " critical development ". This is a fundamental phase that normally takes place from birth to early childhood. The brain is highly modulable and adaptable to its environment. It is said to be extremely plastic. Later, in adulthood, cerebral plasticity can occur, but to a lesser extent.
If we take the example of the visual system, an individual who receives no visual stimulation during this critical period will never be able to see properly.
As a result, the critical period is studied by many laboratories around the world, including my own, because it's important to know what factors regulate it, both in neurons and in other brain cells.
Historically, where does your research problem come from?
At the end of the 1980s, scientists demonstrated that injecting immature astrocytes into the adult brain - which had not yet acquired their specialized role - could reopen, i.e. restart, this critical developmental period.
Prior to my thesis, Nathalie Rouach's team had already begun work based on this discovery and consolidated the results presented thirty years ago. My colleagues highlighted what distinguishes immature astrocytes from mature ones : the latter produce a protein called connexin 30. Its sharp increase coincides with the end of the critical period. In its absence, the critical period is prolonged.
The question was then to understand how this protein could act on the closure, i.e. stopping, of the critical period, from a molecular point of view. This was the starting point for my master's internship at 2, followed by my thesis.
You recently published as " copremière " author in Science : what did you prove, and what do you learn from this project ?
In this article, for the first time , we demonstrated how astrocytes regulate the critical developmental period.
Initially, we were groping for proteins that could interact directly or indirectly with connexin 30. To this end, we conducted experiments called cribles . This enabled us to identify a signalling pathway. This is a sort of cascade of reactions, in this case between a multitude of proteins. Ultimately, this cascade enables neurons to retain their plasticity. However, when astrocytes mature, they produce the connexin 30, which has the effect of blocking the chain of reactions. As this increases, neuronal plasticity decreases : the critical developmental period comes to a halt.
Parallel to this work, during the first two years of my thesis, there was all the preparation of the paper for Science. Participating alongside my colleagues in this major project was a very formative and instructive challenge ; I can only take positive note of the fact that I was confronted very early on with the task of writing an article.
The article even made it into the general press, thanks to Le Monde.
A fine " première " for a young doctoral student..
I've never been a brilliant student, and I've often been told that it's only excellent students who can aspire to go on to a thesis, because of the difficulty of getting a doctoral grant. During my time at university, I found it hard to " hatch " among my fellow students. However, I wanted to pursue an academic career, starting with a PhD, and I was right to persevere !
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Rachel Breton is a PhD student at CIRB in the Neuroglial Interactions in Brain Physiopathology team headed by Nathalie Rouach. Her thesis is entitled " Role of astrocytes in synaptic circuit plasticity during critical developmental periods ".
Photos © Patrick Imbert
Interview by Océane Alouda