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Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments
Liang, J.1,2,3,4; Xu, W.1; Hsu, Y-T2,3; Yee, A. X.2,3; Chen, L.2,3; Suedhof, T. C.1
2015-07-01
发表期刊MOLECULAR PSYCHIATRY
ISSN1359-4184
文章类型Article
卷号20期号:7页码:850-859
摘要Abnormal activity in the medial prefrontal cortex (mPFC) is consistently observed in neuropsychiatric disorders, but the mechanisms involved remain unclear. Chronic aberrant excitation and/or inhibition of mPFC neurons were proposed to cause cognitive impairments. However, direct evidence for this hypothesis is lacking because it is technically challenging to control synaptic properties in a chronic and locally restricted, yet specific, manner. Here, we generated conditional knockout (cKO) mice of neuroligin-2 (Nlgn2), a postsynaptic cell-adhesion molecule of inhibitory synapses linked to neuropsychiatric disorders. cKO of Nlgn2 in adult mPFC rendered Nlgn2 protein undetectable after already 2-3 weeks, but induced major reductions in synaptic inhibition after only 6-7 weeks, and caused parallel impairments in anxiety, fear memory and social interaction behaviors. Moreover, cKO of Nlgn2 severely impaired behavioral stimulation of immediate-early gene expression in the mPFC, suggesting that chronic reduction in synaptic inhibition uncoupled the mPFC from experience-dependent inputs. Our results indicate that Nlgn2 is required for continuous maintenance of inhibitory synapses in the adult mPFC, and that chronic impairment of local inhibition disengages the mPFC from its cognitive functions by partially uncoupling the mPFC from experience-induced inputs.
收录类别SCI
语种英语
WOS记录号WOS:000356611800007
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被引频次:35[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/13359
专题中国科学院心理健康重点实验室
作者单位1.Stanford Univ, Howard Hughes Med Inst, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA
2.Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA
3.Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA
4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
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Liang, J.,Xu, W.,Hsu, Y-T,et al. Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments[J]. MOLECULAR PSYCHIATRY,2015,20(7):850-859.
APA Liang, J.,Xu, W.,Hsu, Y-T,Yee, A. X.,Chen, L.,&Suedhof, T. C..(2015).Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments.MOLECULAR PSYCHIATRY,20(7),850-859.
MLA Liang, J.,et al."Conditional neuroligin-2 knockout in adult medial prefrontal cortex links chronic changes in synaptic inhibition to cognitive impairments".MOLECULAR PSYCHIATRY 20.7(2015):850-859.
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