2012 - Present: Investigator - INSERM - Chargé de Recherche de 1ère Classe - HDR
Laboratoire Neuroscience Paris Seine
Sorbonne Université – INSERM U1130 – CNRS UMR 8246
2008 - 2012: Post-doctoral Fellow, Eric Nestler Laboratory, Mount Sinai, NY, USA
2006 - 2008: Post-doctoral Fellow, Eric Nestler Laboratory, UTSW, Dallas, USA
2001 - 2005: Graduate student, Bruno Giros Laboratory, Creteil, France
Our understanding of neuroplasticity has evolved significantly over the last quarter century. The composition of the extracellular matrix, in particular, was shown to profoundly affect the molecular mechanisms of synaptic plasticity, learning and memory. Matricellular proteins, which include thrombospondins, tenascin C, SPARC and its homolog hevin, represent a relatively unexplored family of proteins that mediate interaction between cells and the extracellular matrix but do not serve primarily structural roles. Most of these proteins are expressed in the brain, where they play an important role during development, in particular in neuronal migration and synaptogenesis. However, their mode of action in adult neuroplasticity is poorly understood. Our team explores the role of matricellular proteins in experience-dependent plasticity and in particular in stress-induced depression and the mechanisms of drug addiction.
Our research has found that hevin is induced by chronic social stress in the nucleus accumbens, a key brain reward region, only in resilient individuals (Vialou et al., 2010). Its overexpression in susceptible mice reversed social avoidance, indicating that induction of hevin is required for resilience to social defeat-induced aversion and anhedonia. Because hevin has anti-adhesive and synaptogenic properties, it could be implicated in the synaptic plasticity underlying positive affect and motivation.
We are now exploring the role of hevin in substance abuse using cell-specific genetic manipulation, RNA interference and chemo-genetics combined with behavioral analysis of drug reward. Using double fluorescent in situ hybridization, we recently showed that hevin has a distinct cellular distribution compared to other matricellular proteins. Hevin is prominently expressed in astrocytes and parvalbumin interneurons in both mouse and human adult brains (Mongrédien et al., 2019). We are also using complementary approaches such as in vitro molecular manipulations of hevin on primary cultures to understand how hevin is regulated and activated in astrocytes and neurons.
Selected references
Expertise: neuropharmacology, neuroanatomy, DREADD, in vivo fiber photometry, GCaMP, RNAi, molecular biology, primary astrocytic cultures, viral-mediated gene transfer, animal models of depression, anxiety and addiction