Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

• Published in: PLoS biology 2019-03, Vol.17 (3), p.e2007097-e2007097
• Main Authors: Teng, Ling-Ling, Lu, Guan-Ling, Chiou, Lih-Chu, Lin, Wei-Sheng, Cheng, Ya-Yun, Hsueh, Tai-En, Huang, Yi-Ching, Hwang, Nai-Hsuan, Yeh, Jin-Wei, Liao, Ruey-Ming, Fan, Shou-Zen, Yen, Jui-Hung, Fu, Tsai-Feng, Tsai, Ting-Fen, Wu, Ming-Shiang, Wang, Pei-Yu
• Format: Article
• Language: English
• Subjects: 3-Hydroxybutyric Acid - blood; Amino acids; Animal behavior; Animal cognition; Animals; Biology and Life Sciences; Biosynthesis; Blotting, Western; Brain; Cellular signal transduction; Cognitive ability; Complexity; Corticosterone - blood; Deactivation; Dendritic spines; Diabetes; Diet; Dietary intake; Dietary restrictions; Direct reduction; Electrophysiology; Funding; Glucose Tolerance Test; Hippocampus; Hippocampus - cytology; Hippocampus - metabolism; Hospitals; Inactivation; Insects; Insurance claims; Investigations; Kinases; Long-term potentiation; Long-Term Potentiation - physiology; Male; Mechanistic Target of Rapamycin Complex 1 - genetics; Mechanistic Target of Rapamycin Complex 1 - metabolism; Medicine; Medicine and Health Sciences; Memory; Memory - physiology; Mice; Mice, Inbred C57BL; Neurobiology; Neurons; Neurons - cytology; Neurons - metabolism; Neurosciences; Nutrient deficiency; Observations; Physiological aspects; Physiological effects; Proteins; Rapamycin; Receptors; Receptors, Serotonin - genetics; Receptors, Serotonin - metabolism; RNA, Messenger - metabolism; Serotonin; Serotonin - blood; Signal Transduction - genetics; Signal Transduction - physiology; Signaling; Spine; Supervision; TOR protein; Trends; Tryptophan
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.2007097

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.