Reduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Mice

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dc.contributor.authorZhou, Xinyien
dc.contributor.authorWu, Bifengen
dc.contributor.authorLiu, Wenhaoen
dc.contributor.authorXiao, Qianen
dc.contributor.authorHe, Weien
dc.contributor.authorZhou, Yingen
dc.contributor.authorWei, Pengfeien
dc.contributor.authorZhang, Xuen
dc.contributor.authorLiu, Yueen
dc.contributor.authorWang, Jieen
dc.contributor.authorHe, Jufangen
dc.contributor.authorZhang, Zhigangen
dc.contributor.authorLi, Weidongen
dc.contributor.authorWang, Lipingen
dc.contributor.authorTu, Jieen
dc.date.accessioned2021-07-22T14:48:03Zen
dc.date.available2021-07-22T14:48:03Zen
dc.date.issued2021-06-18en
dc.description.abstractA strong animal survival instinct is to approach objects and situations that are of benefit and to avoid risk. In humans, a large proportion of mental disorders are accompanied by impairments in risk avoidance. One of the most important genes involved in mental disorders is disrupted-in-schizophrenia-1 (DISC1), and animal models in which this gene has some level of dysfunction show emotion-related impairments. However, it is not known whether DISC1 mouse models have an impairment in avoiding potential risks. In the present study, we used DISC1-N terminal truncation (DISC1-N-TM) mice to investigate risk avoidance and found that these mice were impaired in risk avoidance on the elevated plus maze (EPM) and showed reduced social preference in a three-chamber social interaction test. Following EPM tests, c-Fos expression levels indicated that the nucleus accumbens (NAc) was associated with risk-avoidance behavior in DISC1-N-TM mice. In addition, in vivo electrophysiological recordings following tamoxifen administration showed that the firing rates of fast-spiking neurons (FS) in the NAc were significantly lower in DISC1-N-TM mice than in wild-type (WT) mice. In addition, in vitro patch clamp recording revealed that the frequency of action potentials stimulated by current injection was lower in parvalbumin (PV) neurons in the NAc of DISC1-N-TM mice than in WT controls. The impairment of risk avoidance in DISC1-N-TM mice was rescued using optogenetic tools that activated NAcPV neurons. Finally, inhibition of the activity of NAcPV neurons in PV-Cre mice mimicked the risk-avoidance impairment found in DISC1-N-TM mice during tests on the elevated zero maze. Taken together, our findings confirm an impairment in risk avoidance in DISC1-N-TM mice and suggest that reduced excitability of NAcPV neurons is responsible.en
dc.description.notesThis work was supported by the National Natural Science Foundation of China (31671116, 31761163005, 31800881, and 91132306), the International Big Science Program Cultivation Project of Chinese Academy of Sciences (172644KYS820170004), the External Cooperation Program of the Chinese Academy of Sciences (172644KYSB20160057), Science and Technology Program of Guangzhou Municipality (202007030001), the Key-Area Research and Development Program of Guangdong Province (2018B030331001 and 2018B03033600), and Shenzhen Government Basic Research Grants (JCYJ20200109115405930 and JCYJ20200109150717745). We thank Mr. ZB Xu and Mr. BF Liu for their help in transgenic mouse husbandry and phenotyping. We are grateful to Ms. NN Li for the help in virus packaging.en
dc.description.sponsorshipNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31671116, 31761163005, 31800881, 91132306]; International Big Science Program Cultivation Project of Chinese Academy of Sciences [172644KYS820170004]; External Cooperation Program of the Chinese Academy of SciencesChinese Academy of Sciences [172644KYSB20160057]; Science and Technology Program of Guangzhou Municipality [202007030001]; Key-Area Research and Development Program of Guangdong Province [2018B030331001, 2018B03033600]; Shenzhen Government Basic Research Grants [JCYJ20200109115405930, JCYJ20200109150717745]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1007/s12264-021-00731-7en
dc.identifier.eissn1995-8218en
dc.identifier.issn1673-7067en
dc.identifier.pmid34143365en
dc.identifier.urihttp://hdl.handle.net/10919/104254en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectDISC1en
dc.subjectRisk avoidanceen
dc.subjectParvalbuminen
dc.subjectNucleus accumbensen
dc.titleReduced Firing of Nucleus Accumbens Parvalbumin Interneurons Impairs Risk Avoidance in DISC1 Transgenic Miceen
dc.title.serialNeuroscience Bulletinen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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