AUTHOR=Yao Di , Li Rong , Kora Musa , Huang Hongqing , Liu Xinghua , Gong Song TITLE=Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice JOURNAL=Frontiers in Aging Neuroscience VOLUME=Volume 15 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2023.1142055 DOI=10.3389/fnagi.2023.1142055 ISSN=1663-4365 ABSTRACT=Alzheimer's disease (AD), a progressive neurodegenerative disease that manifests as cognitive impairment, is often accompanied by anxiety. Transient stress enhances the activity of VTAVgat cells for several hours, allowing them to exert a sustained sleep effect. We hypothesized that activation of VTAVgat neurons would reduce anxiety in APP/PS1 mice. We found that acute social defeat stress (SDS) led to anxiety in APP/PS1 mice, as seen in the open field test and elevated plus-arm test. Activation of VTAVgat neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTAVgat neurons improved sleep quality and relieved SDS-induced anxiety. The anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice. In conclusion, the activation of VTAVgat neurons alleviated SDS-induced anxiety in APP/PS1 mice and may be a potential way to treat anxiety in AD.