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Sonia Garel

Brain Development and Plasticity

Our general goal is to understand how functional forebrain circuits, which enable sensory perception, motor responses and cognition, wired up during development. Forebrain circuits begin to be established in the embryo by intrinsic developmental programs that coordinate the assembly of millions of neurons via a complex choreography of neuronal migration and axonal navigation. In addition, intrinsic programs can be perturbed by maternal environment, as illustrated by the fact that prenatal inflammation constitutes a major risk factor for neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. Understanding how embryonic programs and maternal signals control forebrain wiring is thus essential not only to progress in our comprehension of cerebral morphogenesis but also to provide a framework for assessing the etiology of neuropsychiatric disorders.
To this aim, we are examining how migration shapes the assembly of forebrain circuits, how such circuits establish long-range axonal connections and how microglia, the brain resident macrophages that are activated by prenatal inflammation, contributes to both processes. We are addressing these issues using a combination of experimental approaches in mice, which allow the easy manipulation of structures, genes and environmental factors.

Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring.
Riva M, Genescu I, Habermacher C, Orduz D, Ledonne F, Rijli FM, López-Bendito G, Coppola E, Garel S, Angulo MC, Pierani A.
Elife. 2019 Dec 31;8:e50503.

Biphasic Impact of Prenatal Inflammation and Macrophage Depletion on the Wiring of Neocortical Inhibitory Circuits.
Thion MS, Mosser CA, Férézou I, Grisel P, Baptista S, Low D, Ginhoux F, Garel S, Audinat E.
Cell Rep. 2019 Jul 30;28(5):1119-1126

Active intermixing of indirect and direct neurons builds the striatal mosaic.
Tinterri A, Menardy F, Diana MA, Lokmane L, Keita M, Coulpier F, Lemoine S, Mailhes C, Mathieu B, Merchan-Sala P, Campbell K, Gyory I, Grosschedl R, Popa D, Garel S. Nat Commun. 2018 Nov 9;9(1):4725.

Microglia and early brain development: An intimate journey.
Thion MS, Ginhoux F, Garel S.
Science. 2018 Oct 12;362(6411):185-189.

Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner.
Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JKY, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S.
Cell. 2018 Jan 25;172(3):500-516.e16.

Reallocation of Olfactory Cajal-Retzius Cells Shapes Neocortex Architecture.
de Frutos CA, Bouvier G, Arai Y, Thion MS, Lokmane L, Keita M, Garcia-Dominguez M, Charnay P, Hirata T, Riethmacher D, Grove EA, Tissir F, Casado M, Pierani A, Garel S.
Neuron. 2016 Oct 19;92(2):435-448.

axonal tracing showing thalamocortical (green) and corticothalamic (red) (…)
axonal tracing showing thalamocortical (green) and corticothalamic (red) recirpocal connections
migration of corridor neurons (green) open the path for thalamic axons (red)
migration of corridor neurons (green) open the path for thalamic axons (red)