title: [Synapse maturation and autism: learning from neuroligin model mice].
abstract: Autism is a neurodevelopmental disorder characterized by impairments in social interaction, communication, and restricted and repetitive behavior. Synaptic defects have been implicated in autism; nevertheless, the cause is still largely unknown. A mutation that substitutes cysteine for arginine at residue 451 of Neuroligin-3 (R451C) is the first monogenic mutation identified in idiopathic autism patients. To study the relationship between this mutation and autism, we generated knock-in mice that recapitulated this mutation. The knock-in mice were born and grew up normally without showing any major physical phenotypes, but showed a deficit in social interaction. We studied synaptic function in the layer II/III pyramidal neurons in the somatosensory cortex and found inhibitory synaptic transmission was enhanced in the knock-in mice. The administration of GABA blocker rescued social interaction, suggesting that this caused autistic behavior in these mice. We also found, by Morris water maze test, that spatial learning and memory were significantly enhanced in the knock-in mice. Electrophysiology in the CA1 region of the hippocampus revealed that LTP, the NMDA/AMPA ratio, and NR2B function were enhanced, indicating that synaptic maturation was impaired in the knock-in mice. This may cause the deficit in social behavior and extraordinary memory ability occasionally seen in autistic patients.
authors: Katsuhiko
authors: K
authors: Tabuchi
authors: WenHsin
authors: W
authors: Chang
authors: WenHsin
authors: WH
authors: Hang
authors: Nur Farehan
authors: NF
authors: Asgar
authors: Nur Farehan Mohamed
authors: NF
authors: Asgar
authors: Gopal
authors: G
authors: Pramanik
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012919:Social Behavior; D013569:Synapses / Q000235:genetics* / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C098004:neuroligin 3