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Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats
Tian, Yonglu1,2; Yang, Chaojuan1; Shang, Shujiang1; Cai, Yijun3; Deng, Xiaofei4; Zhang, Jian1; Shao, Feng5; Zhu, Desheng1; Liu, Yunbo6; Chen, Guiquan7; Liang, Jing4; Sun, Qiang3; Qiu, Zilong3; Zhang, Chen1,8
First AuthorTian, Yonglu ; Yang, Chaojuan ; Shang, Shujiang ; Cai, Yijun ; Deng, Xiaofei
Correspondent Emailliangj@psych.ac.cn ; qsun@ion.ac.cn ; zqiu@ion.ac.cn ; h.zhang@pku.edu.cn
Contribution Rank4
Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene that inactivate expression of the gene product, the fragile X mental retardation 1 protein (FMRP). In this study, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology to generate Fmr1 knockout (KO) rats by disruption of the fourth exon of the Fmr1 gene. Western blotting analysis confirmed that the FMRP was absent from the brains of the Fmr1 KO rats (Fmr1(exon4-KO)). Electrophysiological analysis revealed that the theta-burst stimulation (TBS)-induced long-term potentiation (LTP) and the low-frequency stimulus (LFS)-induced long-term depression (LTD) were decreased in the hippocampal Schaffer collateral pathway of the Fmr1(exon4-KO) rats. Short-term plasticity, measured as the paired-pulse ratio, remained normal in the KO rats. The synaptic strength mediated by the a -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) was also impaired. Consistent with previous reports, the Fmr1(exon4-KO) rats demonstrated an enhanced 3,5-dihydroxyphenylglycine (DHPG)-induced LTD in the present study, and this enhancement is insensitive to protein translation. In addition, the Fmr1(exon4-KO) rats showed deficits in the probe trial in the Morris water maze test. These results demonstrate that deletion of the Fmr1 gene in rats specifically impairs long-term synaptic plasticity and hippocampus-dependent learning in a manner resembling the key symptoms of FXS. Furthermore, the Fmr1(exon4-KO) rats displayed impaired social interaction and macroorchidism, the results consistent with those observed in patients with FXS. Thus, Fmr1exon4 KO rats constitute a novel rat model of FXS that complements existing mouse models.

KeywordFXS hippocampus long-term plasticity spatial learning intellectual disability
2017-08-28
Language英语
DOI10.3389/fnmol.2017.00269
Source PublicationFRONTIERS IN MOLECULAR NEUROSCIENCE
ISSN1662-5099
Volume10Issue:0Pages:1-14
SubtypeArticle
Indexed BySCI
WOS KeywordFRAGILE-X-SYNDROME ; SPONTANEOUSLY HYPERTENSIVE-RAT ; MENTAL-RETARDATION PROTEIN ; KNOCKOUT MICE ; MOUSE MODEL ; SYNAPTIC PLASTICITY ; SOCIAL-BEHAVIOR ; POTENTIATION ; GENE ; EXPRESSION
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000409065700001
QuartileQ1
Citation statistics
Cited Times:25[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/21899
Collection中国科学院心理健康重点实验室
Corresponding AuthorLiang, Jing; Sun, Qiang; Qiu, Zilong; Zhang, Chen
Affiliation1.State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China
2.Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
3.CAS Key Laboratory of Primate Neurobiology, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
4.Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
5.Department of Psychology, Peking University, Beijing, China
6.Institute of Laboratory Animal Science, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, China
7.MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China
8.Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
Corresponding Author AffilicationInstitute of Psychology, Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Tian, Yonglu,Yang, Chaojuan,Shang, Shujiang,et al. Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats[J]. FRONTIERS IN MOLECULAR NEUROSCIENCE,2017,10(0):1-14.
APA Tian, Yonglu.,Yang, Chaojuan.,Shang, Shujiang.,Cai, Yijun.,Deng, Xiaofei.,...&Zhang, Chen.(2017).Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats.FRONTIERS IN MOLECULAR NEUROSCIENCE,10(0),1-14.
MLA Tian, Yonglu,et al."Loss of FMRP Impaired Hippocampal Long-Term Plasticity and Spatial Learning in Rats".FRONTIERS IN MOLECULAR NEUROSCIENCE 10.0(2017):1-14.
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