Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus

作者全名："Ma, Li; Wang, Jing; Ge, Jianlong; Wang, Yuan; Zhang, Wei; Du, Yuanning; Luo, Jun; Li, Yangping; Wang, Feng; Fan, Guoping; Chen, Rong; Yao, Bing; Zhao, Zhen; Guo, Ming-Lei; Kim, Woong-Ki; Chai, Yang; Chen, Jian-Fu"

作者地址："[Ma, Li; Ge, Jianlong; Wang, Yuan; Zhang, Wei; Du, Yuanning; Luo, Jun; Chai, Yang; Chen, Jian-Fu] Univ Southern Calif USC, Ctr Craniofacial Mol Biol, Los Angeles, CA 90007 USA; [Wang, Jing; Fan, Guoping] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA; [Ge, Jianlong] Univ Texas MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Houston, TX 77030 USA; [Wang, Yuan] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, Chengdu, Peoples R China; [Luo, Jun] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Li, Yangping; Wang, Feng; Yao, Bing] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA; [Chen, Rong] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA; [Zhao, Zhen] Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA 90007 USA; [Guo, Ming-Lei] Eastern Virginia Med Sch, Dept Pathol & Anat, Norfolk, VA 23501 USA; [Kim, Woong-Ki] Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23501 USA"

通信作者："Chen, JF (corresponding author), Univ Southern Calif USC, Ctr Craniofacial Mol Biol, Los Angeles, CA 90007 USA."

来源：EMBO REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000670331300001

JCR分区：Q1

影响因子：7.7

年份：2021

卷号：22

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：chemogenetics; mouse behaviors; neural circuit; Zika virus

摘要："Zika virus (ZIKV) infection during pregnancy is linked to various developmental brain disorders. Infants who are asymptomatic at birth might have postnatal neurocognitive complications. However, animal models recapitulating these neurocognitive phenotypes are lacking, and the circuit mechanism underlying behavioral abnormalities is unknown. Here, we show that ZIKV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic-like behaviors including repetitive self-grooming and impaired social memory in offspring. In the medial prefrontal cortex (mPFC), ZIKV-affected offspring mice exhibit excitation and inhibition imbalance and increased cortical activity. This could be explained by dysregulation of inhibitory neurons and synapses, and elevated neural activity input from mPFC-projecting ventral hippocampus (vHIP) neurons. We find structure alterations in the synaptic connections and pattern of vHIP innervation of mPFC neurons, leading to hyperconnectivity of the vHIP-mPFC pathway. Decreasing the activity of mPFC-projecting vHIP neurons with a chemogenetic strategy rescues social memory deficits in ZIKV offspring mice. Our studies reveal a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV."

基金机构："Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry at the University of Southern California; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01NS097231, R01NS096176]"

基金资助正文："We thank Chen laboratory colleagues for stimulating discussions. We are grateful for Bridget Samuels's critical reading of the manuscript. Chen laboratory is supported by funds from the Associate Dean of Research Fund from the Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry at the University of Southern California, and grants R01NS097231 (J.C.) and R01NS096176 (J.C.) from the National Institutes of Health."