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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; Jing Liang; Qiang Sun; Zilong Qiu; Chen Zhang
2017-08-28
发表期刊FRONTIERS IN MOLECULAR NEUROSCIENCE
通讯作者邮箱liangj@psych.ac.cn ; qsun@ion.ac.cn ; zqiu@ion.ac.cn ; h.zhang@pku.edu.cn
ISSN1662-5099
文章类型Article
卷号10期号:0页码:1-14
摘要

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.

关键词FXS hippocampus long-term plasticity spatial learning intellectual disability
DOI10.3389/fnmol.2017.00269
收录类别SCI
语种英语
项目资助者National Key Research and Development Program of China(2017YFA0105201 ; National Science Foundation of China(31670842) ; Beijing Municipal Science and Technology Commission(Z161100002616021 ; Seeding Grant for Medicine and Life Sciences of Peking University(2014-MB-11) ; 2012YQ03026004 ; Z161100000216154) ; 2014CB942804)
WOS研究方向Neurosciences & Neurology
WOS类目Neurosciences
WOS记录号WOS:000409065700001
WOS标题词Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]FRAGILE-X-SYNDROME ; SPONTANEOUSLY HYPERTENSIVE-RAT ; MENTAL-RETARDATION PROTEIN ; KNOCKOUT MICE ; MOUSE MODEL ; SYNAPTIC PLASTICITY ; SOCIAL-BEHAVIOR ; POTENTIATION ; GENE ; EXPRESSION
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/21899
专题中国科学院心理健康重点实验室
通讯作者Jing Liang; Qiang Sun; Zilong Qiu; Chen Zhang
作者单位1.Peking Univ, State Key Lab Membrane Biol, Sch Life Sci, Peking Univ IDG McGovern Inst Brain Res, Beijing, Peoples R China
2.Peking Univ, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Neurosci, CAS Key Lab Primate Neurobiol, Shanghai, Peoples R China
4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China
5.Peking Univ, Dept Psychol, Beijing, Peoples R China
6.Chinese Acad Med Sci, Peking Union Med Coll, Inst Lab Anim Sci, Beijing, Peoples R China
7.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing, Jiangsu, Peoples R China
8.Peking Univ, Key Lab Neurosci, Minist Educ, Natl Hlth & Family Planning Commiss, Beijing, Peoples R China
推荐引用方式
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.,...&Chen Zhang.(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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