Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism

Stéphane J. Baudouin, Julien Gaudias, Stefan Gerharz, Laetitia Hatstatt, Kuikui Zhou, Pradeep Punnakkal, Kenji Tanaka, Will Spooren, Rene Hen, Chris I. De Zeeuw, Kaspar Vogt, Peter Scheiffele

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158 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)128-132
Number of pages5
JournalScience
Volume338
Issue number6103
DOIs
Publication statusPublished - 2012 Oct 5

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Autistic Disorder
Rodentia
Neuronal Plasticity
Fragile X Syndrome
Metabotropic Glutamate Receptors
Genetic Heterogeneity
Knockout Mice
Phenotype
Mutation

ASJC Scopus subject areas

  • General

Cite this

Baudouin, S. J., Gaudias, J., Gerharz, S., Hatstatt, L., Zhou, K., Punnakkal, P., ... Scheiffele, P. (2012). Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science, 338(6103), 128-132. https://doi.org/10.1126/science.1224159

Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. / Baudouin, Stéphane J.; Gaudias, Julien; Gerharz, Stefan; Hatstatt, Laetitia; Zhou, Kuikui; Punnakkal, Pradeep; Tanaka, Kenji; Spooren, Will; Hen, Rene; De Zeeuw, Chris I.; Vogt, Kaspar; Scheiffele, Peter.

In: Science, Vol. 338, No. 6103, 05.10.2012, p. 128-132.

Research output: Contribution to journalArticle

Baudouin, SJ, Gaudias, J, Gerharz, S, Hatstatt, L, Zhou, K, Punnakkal, P, Tanaka, K, Spooren, W, Hen, R, De Zeeuw, CI, Vogt, K & Scheiffele, P 2012, 'Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism', Science, vol. 338, no. 6103, pp. 128-132. https://doi.org/10.1126/science.1224159
Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P et al. Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. Science. 2012 Oct 5;338(6103):128-132. https://doi.org/10.1126/science.1224159
Baudouin, Stéphane J. ; Gaudias, Julien ; Gerharz, Stefan ; Hatstatt, Laetitia ; Zhou, Kuikui ; Punnakkal, Pradeep ; Tanaka, Kenji ; Spooren, Will ; Hen, Rene ; De Zeeuw, Chris I. ; Vogt, Kaspar ; Scheiffele, Peter. / Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism. In: Science. 2012 ; Vol. 338, No. 6103. pp. 128-132.
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