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Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice

 Chae-Seok Lim  ;  Hyopil Kim  ;  Nam-Kyung Yu  ;  Sukjae Joshua Kang  ;  TaeHyun Kim  ;  Hyoung-Gon Ko  ;  Jaehyun Lee  ;  Jung-eun Yang  ;  Hyun-Hee Ryu  ;  Taesung Park  ;  Jungsoo Gim  ;  Hye Jin Nam  ;  Sung Hee Baek  ;  Stephanie Wegener  ;  Dietmar Schmitz  ;  Tobias M. Boeckers  ;  Min Goo Lee  ;  Eunjoon Kim  ;  Jae-Hyung Lee  ;  Yong-Seok Lee  ;  Bong-Kiun Kaang 
 NEUROPHARMACOLOGY, Vol.112(Pt. A) : 104-112, 2017 
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Animals ; Autism Spectrum Disorder/physiopathology ; CA1 Region, Hippocampal/physiology* ; Inhibitory Postsynaptic Potentials* ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mutation ; Nerve Tissue Proteins/genetics ; Nerve Tissue ; Proteins/metabolism* ; Neurons/physiology ; Receptors, GABA-A/genetics ; Receptors, GABA-A/metabolism ; Social Behavior ; Spatial Memory/physiology*
Autism spectrum disorders ; Gabra2 ; I/E ratio ; Shank2 ; Spatial memory
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 GABAA receptor 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'.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
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