Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism

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...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2012-10, Vol.338 (6103), p.128-132
Main Authors: Baudouin, Stéphane J., Gaudias, Julien, Gerharz, Stefan, Hatstatt, Laetitia, Zhou, Kuikui, Punnakkal, Pradeep, Tanaka, Kenji F., Spooren, Will, Hen, Rene, De Zeeuw, Chris I., Vogt, Kaspar, Scheiffele, Peter
Format: Article
Language:English
Subjects:
Animals
Autism
Autistic disorder
Autistic Disorder - physiopathology
Behavioral neuroscience
Biological and medical sciences
Cell Adhesion Molecules, Neuronal - genetics
Cell Adhesion Molecules, Neuronal - metabolism
Cerebellum
Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...)
Disease Models, Animal
Fragile X syndrome
Fragile X Syndrome - genetics
Fragile X Syndrome - physiopathology
Fundamental and applied biological sciences. Psychology
Genetics
Genotype & phenotype
Male
Medical genetics
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular biology
Mutation
Nerve Net - metabolism
Nerve Net - physiopathology
Nerve Net - ultrastructure
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neuronal Plasticity
Neurons
Neurotransmitters
Phenotypes
Rodents
Social interaction
Synapses
Synapses - metabolism
Synapses - physiology
Synapses - ultrastructure
T tests
Vertebrates: nervous system and sense organs
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1224159