作者
Remzi Karayol, Lucian Medrihan, Jennifer L Warner-Schmidt, Ben W Fait, Meghana N Rao, Eva B Holzner, Paul Greengard, Nathaniel Heintz, Eric F Schmidt
发表日期
2021/6
期刊
Molecular psychiatry
卷号
26
期号
6
页码范围
2334-2349
出版商
Nature Publishing Group UK
简介
Serotonin receptor 4 (5-HT4R) plays an important role in regulating mood, anxiety, and cognition, and drugs that activate this receptor have fast-acting antidepressant (AD)-like effects in preclinical models. However, 5-HT4R is widely expressed throughout the central nervous system (CNS) and periphery, making it difficult to pinpoint the cell types and circuits underlying its effects. Therefore, we generated a Cre-dependent 5-HT4R knockout mouse line to dissect the function of 5-HT4R in specific brain regions and cell types. We show that the loss of functional 5-HT4R specifically from excitatory neurons of hippocampus led to robust AD-like behavioral responses and an elevation in baseline anxiety. 5-HT4R was necessary to maintain the proper excitability of dentate gyrus (DG) granule cells and cell type-specific molecular profiling revealed a dysregulation of genes necessary for normal neural function and plasticity …
学术搜索中的文章
R Karayol, L Medrihan, JL Warner-Schmidt, BW Fait… - Molecular psychiatry, 2021