Postsynaptic gephyrin clustering controls the development of adult-born granule cells in the olfactory bulb

The Journal of Comparative Neurology
Francine DeprezJean-Marc Fritschy

Abstract

In adult rodent olfactory bulb, GABAergic signaling regulates migration, differentiation, and synaptic integration of newborn granule cells (GCs), migrating from the subventricular zone. Here we show that these effects depend on the formation of a postsynaptic scaffold organized by gephyrin-the main scaffolding protein of GABAergic synapses, which anchors receptors and signaling molecules to the postsynaptic density-and are regulated by the phosphorylation status of gephyrin. Using lentiviral vectors to selectively transfect adult-born GCs, we observed that overexpression of the phospho-deficient gephyrin mutant eGFP-gephyrin(S270A), which facilitates the formation of supernumerary GABAergic synapses in vitro, favors dendritic branching and the formation of transient GABAergic synapses on spines, identified by the presence of α2-GABAA Rs. In contrast, overexpression of the dominant-negative eGFP-gephyrin(L2B) (a chimera that is enzymatically active but clustering defective), curtailed dendritic growth, spine formation, and long-term survival of GCs, pointing to the essential role of gephyrin cluster formation for its function. We could exclude any gephyrin overexpression artifacts, as GCs infected with eGFP-gephyrin were compar...Continue Reading

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Citations

Feb 19, 2019·The Journal of Comparative Neurology·Ida Luisa BoccalaroLena Rubi
Jul 1, 2020·The European Journal of Neuroscience·Ida Luisa BoccalaroLena Rubi
Jun 22, 2018·Scientific Reports·Delphine HardyArmen Saghatelyan

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