title: Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism.
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.
authors.affiliation: Biozentrum of the University of Basel, Basel, Switzerland.
authors.forename: Stéphane J
authors.initials: SJ
authors.lastname: Baudouin
authors.forename: Julien
authors.initials: J
authors.lastname: Gaudias
authors.forename: Stefan
authors.initials: S
authors.lastname: Gerharz
authors.forename: Laetitia
authors.initials: L
authors.lastname: Hatstatt
authors.forename: Kuikui
authors.initials: K
authors.lastname: Zhou
authors.forename: Pradeep
authors.initials: P
authors.lastname: Punnakkal
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Will
authors.initials: W
authors.lastname: Spooren
authors.forename: Rene
authors.initials: R
authors.lastname: Hen
authors.forename: Chris I
authors.initials: CI
authors.lastname: De Zeeuw
authors.forename: Kaspar
authors.initials: K
authors.lastname: Vogt
authors.forename: Peter
authors.initials: P
authors.lastname: Scheiffele
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005600:Fragile X Syndrome / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D013569:Synapses / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C098004:neuroligin 3