Teng, Ling-LingLu, Guan-LingChiou, Lih-ChuLin, Wei-ShengCheng, Ya-YunHsueh, Tai-EnHuang, Yi-ChingHwang, Nai-HsuanYeh, Jin-WeiLiao, Ruey-MingFan, Shou-ZenYen, Jui-HungFu, Tsai-FengTsai, Ting-FenWu, Ming-ShiangWang, Pei-Yu2019-08-082019-08-082019-03-18Teng, L. L., Lu, G. L., Chiou, L. C., Lin, W. S., Cheng, Y. Y., Hsueh, T. E., … Wang, P. Y. (2019). Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement. PLoS biology, 17(3), e2007097. doi:10.1371/journal.pbio.2007097https://hdl.handle.net/1805/20245Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesDietary restrictionCalorie restrictionHydroxytryptamine receptor 6Serotonin receptor 5Article