PLoS Biology (Mar 2019)

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

DOI
https://doi.org/10.1371/journal.pbio.2007097
Journal volume & issue
Vol. 17, no. 3
p. e2007097

Abstract

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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 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.