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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Mol. Neurosci. | doi: 10.3389/fnmol.2018.00365

Shank2 mutant mice display hyperactivity insensitive to methylphenidate and reduced flexibility in social motivation, but normal social recognition

 Elodie Ey1, 2*,  Nicolas Torquet3, 4, 5, Fabrice de Chaumont1, 6,  Julie Lévi-Strauss1, 2,  Allain-Thibeault Ferhat1, 2, Anne-Marie Le Sourd1, 2,  Tobias M. Boeckers7, 8 and  Thomas Bourgeon1, 2, 9
  • 1Institut Pasteur, France
  • 2UMR3571 Gènes, synapses et cognition, France
  • 3Laboratoire Neuroscience Paris Seine (IBPS), France
  • 4INSERM U1130 Neurosciences Paris Seine, France
  • 5Sorbonne Universités, France
  • 6UMR3691 Dynamique cellulaire physiologique et pathologique (DC2P), France
  • 7Universität Ulm, Germany
  • 8Institut für Anatomie und Zellbiologie, Medizinische Fakultät, Universität Ulm, Germany
  • 9Université Sorbonne Paris Cité, France

Mouse models of autism can be used to study evolutionarily conserved mechanisms underlying behavioral abnormalities in social communication and repetitive behaviors. SHANK genes code for synaptic scaffolding proteins at excitatory synapses and mutations in all SHANK genes have been associated with autism. Here, we present three behavioral aspects of the mutant mice deleted for exon 16 in Shank2. First, we treated Shank2 mutant mice with methylphenidate to rescue the hyperactivity. Our failure to do so suggests that the hyperactivity displayed by Shank2 mutant mice is not related to the one displayed by the typical mouse models of hyperactivity, and might be more closely related to manic-like behaviors. Second, by testing the effect of group housing and social isolation on social interest, we highlighted that Shank2 mutant mice lack the typical flexibility to modulate social interest, in comparison with wild-type littermates. Finally, we established a new protocol to test for social recognition in a social context. We used this protocol to show that Shank2 mutant mice were able to discriminate familiar and unknown conspecifics in free interactions. Altogether, these studies shed some light on specific aspects of the behavioral defects displayed by the Shank2 mouse model. Such information could be used to orient therapeutic strategies and to design more specific tests to characterize the complex behavior of mouse models of autism.

Keywords: mouse model, autism, Shank2, hyperactivity, Methylphenidate, social motivation, ultrasonic vocalization, social recognition

Received: 12 Jul 2018; Accepted: 13 Sep 2018.

Edited by:

Markus Wöhr, Philipps-Universität Marburg, Germany

Reviewed by:

Maria Passafaro, Università degli Studi di Milano, Italy
Rolf Sprengel, Max-Planck-Institut für medizinische Forschung, Germany  

Copyright: © 2018 Ey, Torquet, de Chaumont, Lévi-Strauss, Ferhat, Le Sourd, Boeckers and Bourgeon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Elodie Ey, Institut Pasteur, Paris, France, eey@pasteur.fr