PSYCH OpenIR  > 中国科学院心理健康重点实验室
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
Source PublicationMOLECULAR PSYCHIATRY
ISSN1359-4184
SubtypeArticle
Volume20Issue:7Pages:850-859
AbstractAbnormal 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.
Indexed BySCI
Language英语
WOS IDWOS:000356611800007
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/13359
Collection中国科学院心理健康重点实验室
Affiliation1.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
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
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.
Files in This Item:
File Name/Size DocType Version Access License
WOS_000356611800007.(1036KB)期刊论文出版稿暂不开放CC BY-NC-SAApplication Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Liang, J.]'s Articles
[Xu, W.]'s Articles
[Hsu, Y-T]'s Articles
Baidu academic
Similar articles in Baidu academic
[Liang, J.]'s Articles
[Xu, W.]'s Articles
[Hsu, Y-T]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Liang, J.]'s Articles
[Xu, W.]'s Articles
[Hsu, Y-T]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.