mTORC2 controls actin polymerization required for consolidation of long-term memory
Wei Huang,Ping Jun Zhu,Shixing Zhang,Hongyi Zhou,Loredana Stoica,Mauricio R. Galiano,Krešimir Krnjević,Gregg Roman,Mauro Costa-Mattioli +8 more
TLDR
It is found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long- term potentiation (L-LTP).Abstract:
A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.read more
Citations
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Journal ArticleDOI
The Molecular and Systems Biology of Memory
TL;DR: In this Review, the molecular, cellular, and circuit mechanisms that underlie how memories are made, stored, retrieved, and lost are examined.
Journal ArticleDOI
The Neurology of mTOR
Jonathan O. Lipton,Mustafa Sahin +1 more
TL;DR: The functions of mTOR signaling in the normal and pathological brain are reviewed, highlighting ongoing efforts to translate the understanding of cellular physiology into direct medical benefit for neurological disorders.
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The restless engram: consolidations never end.
TL;DR: Recent advances in consolidation research, including the reconsolidation of long-term memory items, the brain mechanisms of transformation of the content and of cue-dependency of memory items over time, as well as the role of rest and sleep in consolidating and shaping memories are focused on.
Journal ArticleDOI
m 6 A facilitates hippocampus-dependent learning and memory through YTHDF1
Hailing Shi,Xuliang Zhang,Xuliang Zhang,Yi Lan Weng,Zongyang Lu,Yajing Liu,Zhike Lu,Jianan Li,Piliang Hao,Yu Zhang,Feng Zhang,You Wu,Jary Y. Delgado,Yijing Su,Meera J. Patel,Xiaohua Cao,Bin Shen,Xingxu Huang,Guo Li Ming,Xiaoxi Zhuang,Hongjun Song,Chuan He,Tao Zhou +22 more
TL;DR: It is shown that, through its binding protein YTHDF1, m6A promotes protein translation of target transcripts in response to neuronal stimuli in the adult mouse hippocampus, thereby facilitating learning and memory.
Journal ArticleDOI
Molecular neurobiology of mTOR
Katarzyna Switon,Katarzyna Kotulska,Aleksandra Janusz-Kaminska,Justyna Zmorzynska,Jacek Jaworski +4 more
TL;DR: A comprehensive view ofmTOR in the nervous system is provided, with a special focus on the neuronal functions of mTOR (e.g., control of translation, transcription, and autophagy) that likely underlie the contribution of m TOR to nervous system diseases.
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