Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism

被引：218

作者：

Baudouin, Stephane J. ^{[1
]}

Gaudias, Julien ^{[1
]}

Gerharz, Stefan ^{[1
]}

Hatstatt, Laetitia ^{[1
]}

Zhou, Kuikui ^{[2
]}

Punnakkal, Pradeep ^{[1
]}

Tanaka, Kenji F. ^{[3
,4
]}

Spooren, Will ^{[5
]}

Hen, Rene ^{[3
]}

De Zeeuw, Chris I. ^{[2
,6
]}

Vogt, Kaspar ^{[1
]}

Scheiffele, Peter ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, Basel, Switzerland

[2] Erasmus MC, Dept Neurosci, Rotterdam, Netherlands

[3] Columbia Univ, Dept Neurosci, New York, NY USA

[4] Keio Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan

[5] Hoffmann La Roche AG, Basel, Switzerland

[6] Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands

来源：

SCIENCE | 2012年 / 338卷 / 6103期

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

LONG-TERM DEPRESSION; RARE DE-NOVO; NEUROLIGIN-3; MUTATIONS; RECEPTOR; PROTEIN;

D O I：

10.1126/science.1224159

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：128 / 132

页数：5

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