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

doi:10.1016/j.neuropharm.2016.08.016

. 2017 Jan;112(Pt A):104-112.

doi: 10.1016/j.neuropharm.2016.08.016. Epub 2016 Aug 17.

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

Chae-Seok Lim¹, Hyopil Kim¹, Nam-Kyung Yu¹, Sukjae Joshua Kang¹, TaeHyun Kim¹, Hyoung-Gon Ko¹, Jaehyun Lee¹, Jung-Eun Yang¹, Hyun-Hee Ryu², Taesung Park³, Jungsoo Gim³, Hye Jin Nam⁴, Sung Hee Baek⁴, Stephanie Wegener⁵, Dietmar Schmitz⁵, Tobias M Boeckers⁶, Min Goo Lee⁷, Eunjoon Kim⁸, Jae-Hyung Lee⁹, Yong-Seok Lee¹⁰, Bong-Kiun Kaang¹¹

Affiliations

¹ Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
² Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
³ Department of Statistics, Seoul National University, Seoul, 08826, South Korea.
⁴ Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
⁵ Neuroscience Research Center, Cluster of Excellence NeuroCure, Charite, 10117, Berlin, Germany.
⁶ Institute for Anatomy and Cell Biology, Ulm University, 89081, Ulm, Germany.
⁷ Department of Pharmacology, Severance Biomedical Science Institute, Yonsei University, Seoul, 03722, South Korea.
⁸ Department of Biological Sciences, KAIST, Daejeon, 34141, South Korea.
⁹ 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.
¹⁰ Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea. Electronic address: yongseok7@gmail.com.
¹¹ Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. Electronic address: kaang@snu.ac.kr.

PMID: 27544825
DOI: 10.1016/j.neuropharm.2016.08.016

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

Chae-Seok Lim et al. Neuropharmacology. 2017 Jan.

. 2017 Jan;112(Pt A):104-112.

doi: 10.1016/j.neuropharm.2016.08.016. Epub 2016 Aug 17.

Authors

Affiliations

¹ Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
² Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea.
³ Department of Statistics, Seoul National University, Seoul, 08826, South Korea.
⁴ Laboratory of Molecular and Cellular Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea.
⁵ Neuroscience Research Center, Cluster of Excellence NeuroCure, Charite, 10117, Berlin, Germany.
⁶ Institute for Anatomy and Cell Biology, Ulm University, 89081, Ulm, Germany.
⁷ Department of Pharmacology, Severance Biomedical Science Institute, Yonsei University, Seoul, 03722, South Korea.
⁸ Department of Biological Sciences, KAIST, Daejeon, 34141, South Korea.
⁹ 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.
¹⁰ Department of Physiology, Seoul National University College of Medicine, Seoul, 03080, South Korea. Electronic address: yongseok7@gmail.com.
¹¹ Laboratory of Neurobiology, School of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, 08826, South Korea. Electronic address: kaang@snu.ac.kr.

PMID: 27544825
DOI: 10.1016/j.neuropharm.2016.08.016

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 GABA_A 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'.

Keywords: Autism spectrum disorders; Gabra2; I/E ratio; Shank2; Spatial memory.

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

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

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