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Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice
Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying me...
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Published in: | Neuron (Cambridge, Mass.) Mass.), 2018-03, Vol.97 (6), p.1253-1260.e7 |
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creator | Cao, Wei Lin, Shen Xia, Qiang-qiang Du, Yong-lan Yang, Qian Zhang, Meng-ying Lu, Yi-qing Xu, Jing Duan, Shu-min Xia, Jun Feng, Guoping Xu, Junyu Luo, Jian-hong |
description | Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.
•Gamma and theta oscillation synchrony in mPFC is crucial for social behavior•Principal neuron encoding dysfunction in mPFC is associated with social deficits•Decreased FS IN excitability in mPFC is a causative factor in NL3-R451C KI mice•Patterned optogenetic stimulation of mPFC PV INs rescues social deficit in KI mice
Cao et al. demonstrated FS interneuron deficits and gamma oscillation dysfunction in the mPFC of NL3-R451C KI mice, and the social novelty defect in the KI mice rescued by optogenetic stimulation of the PV interneurons in a theta-gamma nested pattern. |
doi_str_mv | 10.1016/j.neuron.2018.02.001 |
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•Gamma and theta oscillation synchrony in mPFC is crucial for social behavior•Principal neuron encoding dysfunction in mPFC is associated with social deficits•Decreased FS IN excitability in mPFC is a causative factor in NL3-R451C KI mice•Patterned optogenetic stimulation of mPFC PV INs rescues social deficit in KI mice
Cao et al. demonstrated FS interneuron deficits and gamma oscillation dysfunction in the mPFC of NL3-R451C KI mice, and the social novelty defect in the KI mice rescued by optogenetic stimulation of the PV interneurons in a theta-gamma nested pattern.</description><identifier>ISSN: 0896-6273</identifier><identifier>EISSN: 1097-4199</identifier><identifier>DOI: 10.1016/j.neuron.2018.02.001</identifier><identifier>PMID: 29503190</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Autism ; Behavior ; Brain ; Excitability ; Firing pattern ; gamma oscillation ; Hyperactivity ; Interneurons ; mPFC ; Mutation ; Neural coding ; Neuroligin 3 ; Neurons ; optogenetic stimulation ; Parvalbumin ; Prefrontal cortex ; PV interneuron ; Rodents ; Social interaction ; Social interactions ; social novelty ; Synaptogenesis</subject><ispartof>Neuron (Cambridge, Mass.), 2018-03, Vol.97 (6), p.1253-1260.e7</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><rights>2018. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c502t-581f4d3a529644b50e49d894ad9849af0d71016d806ed06f1374eda6a285f0383</citedby><cites>FETCH-LOGICAL-c502t-581f4d3a529644b50e49d894ad9849af0d71016d806ed06f1374eda6a285f0383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29503190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Lin, Shen</creatorcontrib><creatorcontrib>Xia, Qiang-qiang</creatorcontrib><creatorcontrib>Du, Yong-lan</creatorcontrib><creatorcontrib>Yang, Qian</creatorcontrib><creatorcontrib>Zhang, Meng-ying</creatorcontrib><creatorcontrib>Lu, Yi-qing</creatorcontrib><creatorcontrib>Xu, Jing</creatorcontrib><creatorcontrib>Duan, Shu-min</creatorcontrib><creatorcontrib>Xia, Jun</creatorcontrib><creatorcontrib>Feng, Guoping</creatorcontrib><creatorcontrib>Xu, Junyu</creatorcontrib><creatorcontrib>Luo, Jian-hong</creatorcontrib><title>Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice</title><title>Neuron (Cambridge, Mass.)</title><addtitle>Neuron</addtitle><description>Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.
•Gamma and theta oscillation synchrony in mPFC is crucial for social behavior•Principal neuron encoding dysfunction in mPFC is associated with social deficits•Decreased FS IN excitability in mPFC is a causative factor in NL3-R451C KI mice•Patterned optogenetic stimulation of mPFC PV INs rescues social deficit in KI mice
Cao et al. demonstrated FS interneuron deficits and gamma oscillation dysfunction in the mPFC of NL3-R451C KI mice, and the social novelty defect in the KI mice rescued by optogenetic stimulation of the PV interneurons in a theta-gamma nested pattern.</description><subject>Autism</subject><subject>Behavior</subject><subject>Brain</subject><subject>Excitability</subject><subject>Firing pattern</subject><subject>gamma oscillation</subject><subject>Hyperactivity</subject><subject>Interneurons</subject><subject>mPFC</subject><subject>Mutation</subject><subject>Neural coding</subject><subject>Neuroligin 3</subject><subject>Neurons</subject><subject>optogenetic stimulation</subject><subject>Parvalbumin</subject><subject>Prefrontal cortex</subject><subject>PV interneuron</subject><subject>Rodents</subject><subject>Social interaction</subject><subject>Social interactions</subject><subject>social novelty</subject><subject>Synaptogenesis</subject><issn>0896-6273</issn><issn>1097-4199</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kcFu1DAQhi0EokvhDRCyxIVLwthxEvuChLa0ILa0KnC2XHuCvCR2aydIfXsctnDg0JPH0jfjfz4T8pJBzYB1b_d1wCXFUHNgsgZeA7BHZMNA9ZVgSj0mG5CqqzreN0fkWc77AohWsafkiKsWGqZgQ8yZmSZDL7L142hmHwM9ucvDEuyf2gc6XZ5u6Q6Ny3SO9Gu03oz0BAdv_ZxX4MsaY_Q_StnQK9GyLf0cov1Z7ufe4nPyZDBjxhf35zH5fvrh2_Zjtbs4-7R9v6tsC3yuWskG4RrTctUJcd0CCuWkEsYpKZQZwPXr2k5Chw66gTW9QGc6w2U7QCObY_LmMPcmxdsF86wnny2WrQLGJeuiCWQje9UX9PV_6D4uKZR0K9VzJounQokDZVPMOeGgb5KfTLrTDPSaRe_14QvWLqmB62K4tL26H75cT-j-Nf11XoB3BwCLjV8eky7yMVh0PqGdtYv-4Rd-A50-lk4</recordid><startdate>20180321</startdate><enddate>20180321</enddate><creator>Cao, Wei</creator><creator>Lin, Shen</creator><creator>Xia, Qiang-qiang</creator><creator>Du, Yong-lan</creator><creator>Yang, Qian</creator><creator>Zhang, Meng-ying</creator><creator>Lu, Yi-qing</creator><creator>Xu, Jing</creator><creator>Duan, Shu-min</creator><creator>Xia, Jun</creator><creator>Feng, Guoping</creator><creator>Xu, Junyu</creator><creator>Luo, Jian-hong</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20180321</creationdate><title>Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice</title><author>Cao, Wei ; Lin, Shen ; Xia, Qiang-qiang ; Du, Yong-lan ; Yang, Qian ; Zhang, Meng-ying ; Lu, Yi-qing ; Xu, Jing ; Duan, Shu-min ; Xia, Jun ; Feng, Guoping ; Xu, Junyu ; Luo, Jian-hong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c502t-581f4d3a529644b50e49d894ad9849af0d71016d806ed06f1374eda6a285f0383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Autism</topic><topic>Behavior</topic><topic>Brain</topic><topic>Excitability</topic><topic>Firing pattern</topic><topic>gamma oscillation</topic><topic>Hyperactivity</topic><topic>Interneurons</topic><topic>mPFC</topic><topic>Mutation</topic><topic>Neural coding</topic><topic>Neuroligin 3</topic><topic>Neurons</topic><topic>optogenetic stimulation</topic><topic>Parvalbumin</topic><topic>Prefrontal cortex</topic><topic>PV interneuron</topic><topic>Rodents</topic><topic>Social interaction</topic><topic>Social interactions</topic><topic>social novelty</topic><topic>Synaptogenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cao, Wei</creatorcontrib><creatorcontrib>Lin, Shen</creatorcontrib><creatorcontrib>Xia, Qiang-qiang</creatorcontrib><creatorcontrib>Du, Yong-lan</creatorcontrib><creatorcontrib>Yang, Qian</creatorcontrib><creatorcontrib>Zhang, Meng-ying</creatorcontrib><creatorcontrib>Lu, Yi-qing</creatorcontrib><creatorcontrib>Xu, Jing</creatorcontrib><creatorcontrib>Duan, Shu-min</creatorcontrib><creatorcontrib>Xia, Jun</creatorcontrib><creatorcontrib>Feng, Guoping</creatorcontrib><creatorcontrib>Xu, Junyu</creatorcontrib><creatorcontrib>Luo, Jian-hong</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Neuron (Cambridge, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cao, Wei</au><au>Lin, Shen</au><au>Xia, Qiang-qiang</au><au>Du, Yong-lan</au><au>Yang, Qian</au><au>Zhang, Meng-ying</au><au>Lu, Yi-qing</au><au>Xu, Jing</au><au>Duan, Shu-min</au><au>Xia, Jun</au><au>Feng, Guoping</au><au>Xu, Junyu</au><au>Luo, Jian-hong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice</atitle><jtitle>Neuron (Cambridge, Mass.)</jtitle><addtitle>Neuron</addtitle><date>2018-03-21</date><risdate>2018</risdate><volume>97</volume><issue>6</issue><spage>1253</spage><epage>1260.e7</epage><pages>1253-1260.e7</pages><issn>0896-6273</issn><eissn>1097-4199</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.
•Gamma and theta oscillation synchrony in mPFC is crucial for social behavior•Principal neuron encoding dysfunction in mPFC is associated with social deficits•Decreased FS IN excitability in mPFC is a causative factor in NL3-R451C KI mice•Patterned optogenetic stimulation of mPFC PV INs rescues social deficit in KI mice
Cao et al. demonstrated FS interneuron deficits and gamma oscillation dysfunction in the mPFC of NL3-R451C KI mice, and the social novelty defect in the KI mice rescued by optogenetic stimulation of the PV interneurons in a theta-gamma nested pattern.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29503190</pmid><doi>10.1016/j.neuron.2018.02.001</doi><oa>free_for_read</oa></addata></record> |
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subjects | Autism Behavior Brain Excitability Firing pattern gamma oscillation Hyperactivity Interneurons mPFC Mutation Neural coding Neuroligin 3 Neurons optogenetic stimulation Parvalbumin Prefrontal cortex PV interneuron Rodents Social interaction Social interactions social novelty Synaptogenesis |
title | Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice |
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