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Science 338 (6103): 128-132

Copyright © 2012 by the American Association for the Advancement of Science

Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism

Stéphane J. Baudouin,1 Julien Gaudias,1 Stefan Gerharz,1,* Laetitia Hatstatt,1 Kuikui Zhou,2 Pradeep Punnakkal,1 Kenji F. Tanaka,3,4 Will Spooren,5 Rene Hen,3 Chris I. De Zeeuw,2,6 Kaspar Vogt,1 Peter Scheiffele1,{dagger}

Abstract: The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted heterosynaptic competition and perturbed metabotropic glutamate receptor–dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development.

1 Biozentrum of the University of Basel, Basel, Switzerland.
2 Department of Neuroscience, Erasmus MC, Rotterdam, Netherlands.
3 Department of Neuroscience, Columbia University, New York, NY, USA.
4 Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan.
5 Hoffmann-La Roche, Basel, Switzerland.
6 Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.

* Deceased.

{dagger} To whom correspondence should be addressed. E-mail: peter.scheiffele{at}

A Cell Surface Biotinylation Assay to Reveal Membrane-associated Neuronal Cues: Negr1 Regulates Dendritic Arborization.
F. Pischedda, J. Szczurkowska, M. D. Cirnaru, F. Giesert, E. Vezzoli, M. Ueffing, C. Sala, M. Francolini, S. M. Hauck, L. Cancedda, et al. (2014)
Mol. Cell. Proteomics 13, 733-748
   Abstract »    Full Text »    PDF »
Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting.
C. Biesemann, M. Gronborg, E. Luquet, S. P. Wichert, V. Bernard, S. R. Bungers, B. Cooper, F. Varoqueaux, L. Li, J. A. Byrne, et al. (2014)
EMBO J. 33, 157-170
   Abstract »    Full Text »    PDF »
Neuroligins Provide Molecular Links Between Syndromic and Nonsyndromic Autism.
S. K. Singh and C. Eroglu (2013)
Science Signaling 6, re4
   Abstract »    Full Text »    PDF »
Neuroligin1 Drives Synaptic and Behavioral Maturation through Intracellular Interactions.
J. L. Hoy, P. A. Haeger, J. R. L. Constable, R. J. Arias, R. McCallum, M. Kyweriga, L. Davis, E. Schnell, M. Wehr, P. E. Castillo, et al. (2013)
J. Neurosci. 33, 9364-9384
   Abstract »    Full Text »    PDF »
Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling.
E. C. Budreck, O.-B. Kwon, J. H. Jung, S. Baudouin, A. Thommen, H.-S. Kim, Y. Fukazawa, H. Harada, K. Tabuchi, R. Shigemoto, et al. (2013)
PNAS 110, 725-730
   Abstract »    Full Text »    PDF »

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