Serotonin receptor htr6-mediated mtorc1 signaling regulates dietary restriction–induced memory enhancement

Ling Ling Teng, Guan Ling Lu, Lih Chu Chiou, Wei Sheng Lin, Ya Yun Cheng, Tai En Hsueh, Yi Ching Huang, Nai Hsuan Hwang, Jin Wei Yeh, Ruey Ming Liao, Shou Zen Fan, Jui Hung Yen, Tsai Feng Fu, Ting Fen Tsai, Ming Shiang Wu, Pei Yu Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Dietary 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 longterm 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.

Original languageEnglish
Article numbere2007097
Issue number3
StatePublished - Mar 2019


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