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Neural Plasticity
Volume 2019, Article ID 2382639, 11 pages
Research Article

Enhanced Glutamatergic Currents at Birth in Shank3 KO Mice

1Department of Neurobiology, Mediterranean Institute of Neurobiology (INMED), Aix-Marseille University, INSERM U1249, 13273 Marseille Cedex 09, France
2Neurochlore, Ben-Ari Institute of Neuroarcheology (IBEN), Fundamental Research Department, Bâtiment Beret-Delaage, Parc Scientifique et Technologique de Luminy, 13288 Marseille Cedex 09, France

Correspondence should be addressed to Yehezkel Ben-Ari; rf.mresni@ira-neb.lekzehey

Morgane Chiesa and Romain Nardou contributed equally to this work.

Received 21 February 2019; Revised 13 May 2019; Accepted 30 May 2019; Published 3 July 2019

Academic Editor: Victor Anggono

Copyright © 2019 Morgane Chiesa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Autism spectrum disorders (ASD) are neurodevelopmental disorders induced by genetic and environmental factors. In our recent studies, we showed that the GABA developmental shifts during delivery and the second postnatal week are abolished in two rodent models of ASD. Maternal treatment around birth with bumetanide restored the GABA developmental sequence and attenuated the autism pathogenesis in offspring. Clinical trials conducted in parallel confirmed the usefulness of bumetanide treatment to attenuate the symptoms in children with ASD. Collectively, these observations suggest that an alteration of the GABA developmental sequence is a hallmark of ASD. Here, we investigated whether similar alterations occur in the Shank3 mouse model of ASD. We report that in CA3 pyramidal neurons, the driving force and inhibitory action of GABA are not different in naïve and Shank3-mutant age-matched animals at birth and during the second postnatal week. In contrast, the frequency of spontaneous excitatory postsynaptic currents is already enhanced at birth and persists through postnatal day 15. Therefore, in CA3 pyramidal neurons of Shank3-mutant mice, glutamatergic but not GABAergic activity is affected at early developmental stages, hence reflecting the heterogeneity of mechanisms underlying the pathogenesis of ASD.