Long term recovery following a brain lesion during the critical period of plasticity
22nd of May at 2pm in Amphi Physique in Rockefeller Faculty
Jury :
Kretz-Remy Carole, Professeure des Université, Université Claude Bernard Lyon 1, Présidente
Humbert Sandrine, Directrice de recherche, Université Grenoble-Alpes, Rapporteure
Davy Alice, Directrice de recherche, Université Toulouse III Paul Sabatier, Rapporteure
Vanderhaeghen Pierre, Professeur, Katholieke Universitet Leuven, Examinateur
Lewis Tommy, Professeur assistant, Oklahoma Medical Research Foundation, Examinateur
Courchet Julien, Directeur de recherche, Université Claude Bernard Lyon 1, Inserm, Directeur de thèse
Raineteau Olivier, Directeur de recherche, Université Claude Bernard Lyon 1, Inserm, Directeur de thèse
Abstract:
Neural circuits are built at perinatal times and gradually refined during a postnatal period of critical plasticity. During this period, energy metabolism and neuronal maturation are tightly linked. Although lesions of the central nervous system (CNS) occurring during this period recover better than those occurring later in life, they are often associated with long-term cognitive deficits, which suggests that neuronal circuits rewiring is either incomplete or inappropriate. I used chronic neonatal hypoxia, a mouse model of very premature birth, to study the long-term impact of brain injuries on energy metabolism and cortical circuits formation. My work shows alterations of glutamatergic neurons’ dendritic arborizations weeks after the hypoxic insult. These dendritic alterations are paralleled by a global cortical hyperconnectivity as well as a redistribution of short- and long-distance cortical connections. Interestingly, mitochondria morphological and proteomic analysis reveal a reduction in mitochondria protein expression in hypoxic mice brains, suggesting long term metabolic defects. Finally, testing of sociability reveals an impairment for social novelty in young adult hypoxic mice, which amplifies in adulthood. Altogether, my thesis work provides a better knowledge of how early metabolic insults can impact neuronal metabolism, cortical connectivity, as well as associated behaviors later in life.
