CV Science

Corentin Le Magueresse PhD Neuropharmacology

Course and current status

2022-present: team leader

Institut du Fer à Moulin (INSERM & Sorbonne Université), Paris

www.ifm-institute.fr/en/

2013-present: tenured INSERM investigator & project leader

Institut du Fer à Moulin

2006-2013: postdoctoral scientist

University of Heidelberg and German Cancer Research Center (Monyer lab)

2001-2006: PhD student

Institut Pasteur, Paris (Changeux lab) and International School for Advanced Studies, Trieste (Cherubini lab)

Scientific summary

Since the beginning of my scientific career I have been interested in mechanisms sculpting neural circuits during postnatal development. While the basic layout of the brain is first established by genetic programs and intrinsic activity, the developing brain rapidly becomes remarkably plastic, capable of remodeling synaptic connections in response to changing experiences. This experience-dependent sculpting of neuronal circuits peaks during specific time windows called critical periods.

I am currently interested in two forms of critical period plasticity:

1)    During postnatal development, the brain generates an excess of synapses. The inactive fraction of these synapses is eliminated in adolescence, a phenomenon known as synaptic pruning. Synaptic pruning defects have been identified in some brain disorders, particularly schizophrenia. Recent research shows that genes of the complement, a system contributing to innate immunity, mediate synaptic pruning in the brain. Complement genes are also associated with schizophrenia. We investigate the role of distinct complement components in network remodeling and microglia-neuron interactions in the adolescent brain using novel transgenic mouse models, optogenetics, electrophysiology, histology, imaging, and behavioral studies.

2)    A critical period has been well characterized in the visual cortex where permanent changes in neuronal networks take place following transient closure of one eye in young but not in adult mammals. Converging evidence implicates glutamatergic inputs onto parvalbumin-expressing interneurons in the onset of this critical period for visual cortex plasticity. However, the underlying molecular and synaptic mechanisms remain unclear. Using a multidisciplinary approach including novel transgenic mice, viral vectors, and electrophysiology, we study the contribution of specific synaptic proteins to network plasticity during the critical period in visual cortex.

Selected publications:

Druart M, Nosten-Bertrand M^#, Poll S^#, Crux S^#, Nebeling F^#, Delhaye C, Dubois Y, Leboyer M, Tamouza R, Fuhrmann M, Le Magueresse C. Elevated expression of complement C4 in the mouse prefrontal cortex causes schizophrenia-associated phenotypes.   Molecular Psychiatry 26(7):3489-3501 (2021)  ^# equal contribution

Druart M, Groszer M, Le Magueresse C. An Etiological Foxp2 Mutation Impairs Neuronal Gain in Layer VI Cortico-Thalamic Cells through Increased GABA_B/GIRK Signaling. Journal of Neuroscience 40(44):8543-8555 (2020)

Zuccotti A^#, Le Magueresse C^#, Chen M, Neitz A, Monyer H. The transcription factor Fezf2 directs the differentiation of neural stem cells in the subventricular zone toward a cortical phenotype. PNAS 111(29):10726-31 (2014) ^# equal contribution

Le Magueresse C, Monyer H. GABAergic interneurons shape the functional maturation of the cortex. Neuron 77(3):388-405 (2013). Review article.

Le Magueresse C^#, Alfonso J^#, Bark C, Eliava M, Khrulev S, Monyer H. Subventricular zone-derived neuroblasts use vasculature as a scaffold to migrate radially to the cortex. Cerebral Cortex. 22(10):2285-96 (2012) ^# equal contribution

Alfonso J^#, Le Magueresse C^#, Khodosevich K, Monyer H. Diazepam Binding Inhibitor promotes proliferation of neural progenitors in the SVZ by reducing GABA signaling. Cell Stem Cell, 10(1):76-87 (2012).  ^# equal contribution

Le Magueresse C^#, Alfonso J^#, Khodosevich K, Arroyo Martín AA, Bark C, Monyer H. “Small axonless neurons”: postnatally generated neocortical interneurons with delayed functional maturation.  Journal of Neuroscience. 31(46):16731-47 (2011). ^# equal contribution