title: Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice.
abstract: Autism spectrum disorders (ASDs) are a group of developmental disorders that cause variable and heterogeneous phenotypes across three behavioral domains such as atypical social behavior, disrupted communications, and highly restricted and repetitive behaviors. In addition to these core symptoms, other neurological abnormalities are associated with ASD, including intellectual disability (ID). However, the molecular etiology underlying these behavioral heterogeneities in ASD is unclear. Mutations in SHANK2 genes are associated with ASD and ID. Interestingly, two lines of Shank2 knockout mice (e6-7 KO and e7 KO) showed shared and distinct phenotypes. Here, we found that the expression levels of Gabra2, as well as of GABA receptor-mediated inhibitory neurotransmission, are reduced in Shank2 e6-7, but not in e7 KO mice compared with their own wild type littermates. Furthermore, treatment of Shank2 e6-7 KO mice with an allosteric modulator for the GABAAreceptor reverses spatial memory deficits, indicating that reduced inhibitory neurotransmission may cause memory deficits in Shank2 e6-7 KO mice. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Chae-Seok
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Hyopil
authors.initials: H
authors.lastname: Kim
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Nam-Kyung
authors.initials: NK
authors.lastname: Yu
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Sukjae Joshua
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: TaeHyun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Ko
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Yang
authors.affiliation: Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Ryu
authors.affiliation: Department of Statistics, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Statistics, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Jungsoo
authors.initials: J
authors.lastname: Gim
authors.affiliation: Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Neuroscience Research Center, Cluster of Excellence NeuroCure, Charite, 10117, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Wegener
authors.affiliation: Neuroscience Research Center, Cluster of Excellence NeuroCure, Charite, 10117, Berlin, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, 89081, Ulm, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.affiliation: Department of Pharmacology, Severance Biomedical Science Institute, Yonsei University, Seoul, 03722, South Korea.
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, 34141, South Korea.
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Department of Maxillofacial Biomedical Engineering, School of Dentistry, Kyung Hee University, Seoul, 02447, South Korea. Electronic address: jaehlee@khu.ac.kr.
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea. Electronic address: yongseok7@gmail.com.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. Electronic address: kaang@snu.ac.kr.
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D012919:Social Behavior; D065852:Spatial Memory / Q000502:physiology*
chemical_list: C493920:Gabra2 protein, mouse; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C488222:Shank2 protein, mouse
keywords: Autism spectrum disorders; Gabra2; I/E ratio; Shank2; Spatial memory