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シンポジウム Current status and future perspective of autism from both basic neuroscience and clinical research 2S3-1 Atypical brain auditory processing in young children with autism spectrum disorder. Kikuchi Mitsuru，Minabe Yoshio Research Center for Child Mental Development, Kanazawa University, Kanazawa, Japan Magnetoencephalography（MEG）is a noninvasive neuroimaging technique that provides a measure of cortical neural activity on a millisecond time scale with high spatial resolution. In the past decade, a number of previous MEG studies have reported atypical brain responses to auditory stimuli in children with autism spectrum disorder（ASD）. Recently, using a child custom-sized MEG, we demonstrated the atypical brain auditory processing and the atypical developmental trajectory in a component of auditory evoked field（P1m）in young children with ASD. Although further studies are still necessary, we present our recent result from MEG study for young children with ASD and typically developing children. 2S3-2 Modeling Autism Takumi Toru RIKEN BSI Autism is a complex psychiatric illness that has received considerable attention as a developmental brain disorder. Substantial evidence suggests that chromosomal abnormalities including copy number variations contribute to autism risk. The duplication of human chromosome 15q11-q13 is known to be the most frequent cytogenetic abnormality in autism. We have modeled this genetic change in mice using chromosome engineering to generate a 6.3-Mb duplication of the conserved linkage group on mouse chromosome 7. Mice with a paternal duplication display autistic-like behavioral features such as poor social interaction and stereotypical behavior, and exhibit abnormal ultrasonic vocalizations. This chromosome-engineered mouse model for autism seems to replicate various aspects of human autistic phenotypes and validates the relevance of the human chromosome abnormality. This model is a founder mouse for forward genetics of a developmental brain disorder and an invaluable tool for its therapeutic development. I will show our analyses on these mice towards understanding the molecular pathophysiology of autism spectrum disorder. 2S3-3 De-regulation of translation and synaptic function in rodent models of autism Scheiffele Peter Biozentrum of the University of Basel An imbalance of neuronal protein synthesis is emerging as a pathophysiological hallmark in Fragile X Syndrome and some forms of autism. Disease-associated mutations modifying the function of the eIF4F eukaryotic translation initiation factor complex or ribosome processivity result in elevated translation downstream of metabotropic glutamate receptors（mGluR）. However, most autism-associated mutations do not directly impact the translation machinery or its regulators. Thus, it is unknown whether strategies targeting protein synthesis homeostasis are more broadly applicable in neurodevelopmental disorders. We here report that the autism-associated mutation of Nlgn3, a gene encoding the synaptic adhesion molecule, results in an impairment of neuronal mTORC1-dependent signaling, a reduction in eIF4F assembly, and reduced protein synthesis. Pharmacological inhibition of the MAP-kinase pathway, which modulate eIF4F function, restores normal protein synthesis rates in Nlgn3KO mice. Moreover, a brain penetrant inhibitor alleviates several autism-related behavioral deficits in adult Nlgn3KO mice. This work identifies a target for pharmacological intervention in neuronal disorders with perturbed translational homeostasis. 2S3-4 Current status and future perspective of autism from clinical research with oxytocin and neuroimaging Yamasue Hidenori Dept. of Neuropsychiatry, Univ. of Tokyo Autism spectrum disorders, a highly prevalent neurodevelopmental disorder, currently have no established treatment for its core symptoms. The disorders are characterized by two core symptoms including deficits in social communication and interaction, and repetitive and restricted behavior. Since accumulating evidence supports the concept that oxytocin can induce effects on social and affiliative behaviors, the neuropeptide is thought to be a potential therapeutic approach for deficits in social communication and interaction in individuals with autism spectrum disorders. In fact, our previous studies have revealed oxytocin-induced temporal mitigations of autistic behavior and its neural basis such as brain activity. Ongoing studies are further conducting to examine several unresolved issues such as 1）clinically meaningful effects after long-term administrations of oxytocin, 2）bio-markers predicting individual differences in therapeutic effects in advance, and 3）potential genetic and molecular mechanisms of effects of oxytocin on autism spectrum behaviors. In the symposium, integration of previous findings and introductions of ongoing studies will be presented to promote productive interactions with other speakers and audiences from various research fields.