The astrocyte, an intimate partner of neurons.
After obtaining a bachelor's and master's degree in Cellular Biology and Physiology at the University of Bordeaux 2, I realized that understanding how synapses work is a key element in understanding how information is transmitted in the brain. In September 2002, I joined Dr. Dominique Poulain's laboratory (INSERM 378, Morphofunctional Neurobiology unit) to do my DEA internship in Neurosciences and Neuropharmacology, under the supervision of Dr. Stéphane Oliet. This laboratory mainly worked on the plasticity of a neuroendocrine system, the hypothalmo-neuro-pituitary system, involved in several essential functions for our body. During my DEA, I characterized the subtype of metabotropic glutamate receptor involved in regulating the efficacy of glutamatergic and GABAergic synaptic transmission in the supraoptic nucleus.
Very quickly, in contact with Dr. Stéphane Oliet and Dr. Dionysia Theodosis, I realized that to better understand brain transmission, it was necessary to integrate a partner who was previously ignored: the astrocyte. I therefore decided to do my thesis (September 2003 - December 2006) under the supervision of Dr. Stéphane Oliet. First, we demonstrated that the efficacy of glutamatergic synaptic transmission can be increased or decreased persistently in the supra-optic nucleus, as is the case in other structures such as the hippocampus. These long-term synaptic plasticity phenomena are dependent on the activation of NMDA-type postsynaptic glutamatergic receptors. Activation of NMDA receptors requires the concomitant binding of two ligands, glutamate at the glutamate binding site and a coagonist, glycine or D-serine, at the glycine binding site. We have shown that D-serine, synthesized by astrocytes of the supraoptic nucleus, is the only endogenous ligand of the NMDA receptor glycine site in this structure in adults. Our work has shown that astrocytes, by releasing D-serine, control the activity of NMDA receptors and therefore long-term synaptic plasticity.
At the end of my thesis, the classical vision stipulated that astrocytes were able to detect synaptic activity only when it was important and involved the simultaneous activation of several synapses. However, as I showed during my doctoral work that astrocytes control the activity of NMDA receptors under conditions of basal synaptic transmission, at the end of my thesis I was convinced that communication between astrocytes and neurons could be done in response to very low levels of synaptic activity. In January 2007, I joined the laboratory of Professor Richard Robitaille, of the University of Montreal (Montreal, Canada), one of the international leaders in the field of interactions between neurons and glial cells. The work I did under his direction revealed for the first time that astrocytes were able to detect the activity of individual synapses and modulate their functions in return.
In order to better understand the role of astrocytes in synaptic transmission, we need to better understand the morphological interaction of the astrocyte element with the neural elements of the synapse. It is to answer this problem that I carried out a last year of post-doctoral studies (June 2011-September 2012) in the teams of Dr. Stéphane Oliet (Neurocentre Magendie) and Professor Valentin Nägerl (IINS, Bordeaux), a specialist in super-resolution microscopy (STED).
In October 2012, I was recruited from the Centre National de la Recherche Scientifique, in the Glie-neurone Relations group headed by Dr. Stéphane Oliet, at the Neurocentre Magendie. The aim of my work is to better understand how an astrocyte, in close interaction with more than 100,000 synapses, is able to adequately regulate all the synapses with which it interacts. In addition, on the basis of this work I am trying to understand whether a modification of the astrocyte-neurone interaction would be involved in certain brain pathologies.
Mrs Nathalie ROUACH, DR INSERM, Collège de France, Paris (Rapporteur)
Mr Richard ROBITAILLE, Professor, Université de Montréal, Montreal, Candada (Rapporteur)
Mr Luc PELLERIN, Associate Professor, University of Lausanne, Switzerland (Rapporteur)
Mr. Charles BOURQUE, Professor, McGill University, Canada (Examiner)
Mr. Etienne AUDINAT, DR CNRS, Institut de genénomique fonctionnelle, Montpellier (Examiner)
Mr Stéphane OLIET, DR CNRS, Neurocentre Magendie, Bordeaux (Examiner)
Translated with www.DeepL.com/Translator
Date de la soutenance: 23/09/2019 - 14h00
Lieu: Neurocentre Magendie Seminar room