mTORC2 controls actin polymerization required for consolidation of long-term memory
Open accessAbstract
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.
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L-LTP is thought to be a molecular mechanism underlying mnemonic consolidation in CA1 synapses.
“is thought to be a molecular mechanism underlying mnemonic consolidation in CA1 synapses”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Huang et al., 2013
Dopaminergic neurotransmission within the CA1 influences late phase LTP (L-LTP).
“Physiological evidence has indicated that dopaminergic neurotransmission within the CA1 influences late phase LTP (L-LTP)”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Huang et al., 2013
L-LTP requires protein synthesis.
“a phenomenon that requires protein synthesis”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Huang et al., 2013
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- Authors
- Huang, W., Zhu, P. J., Zhang, S., Zhou, H., Stoica, L., Galiano, M., Krnjević, K., Roman, G., & Costa-Mattioli, M.
- Affiliations
- Baylor College of Medicine (US)
- University of Houston (US)
- McGill University (CA)
- Venue
- Nature Neuroscience
- Published
- 2013-03-03
- Volume
- 16
- Issue
- 4
- Pages
- 441-448
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC3615448
- OpenAlex
- W1972346280
- Cited by
- 307
- References
- 71
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 22 · 2023: 16 · 2022: 26 · 2021: 21 · 2020: 19 · 2019: 23 · 2018: 27 · 2017: 28 · 2016: 26 · 2015: 29 · 2014: 23 · 2013: 18 · 2012: 1
- FWCI
- 17.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Conicet (submittedVersion, cc-by-nc-sa)
- Funders
- Vanderbilt University
- National Institutes of Health (076708, 096816)
- National Institute of Mental Health (MH091305, 096816, R01MH096816, MH 096816)
- National Institute of Neurological Disorders and Stroke (NS 076708, R01NS076708)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTORC2, Rictor, actin polymerization, long-term memory consolidation, synaptic plasticity, hippocampal long-term potentiation, actin dynamics, conditional knockout mice, Drosophila
- MeSH terms
- Mechanistic Target of Rapamycin Complex 2, Actins, Animals, Drosophila, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Long-Term Potentiation, Mice, Knockout, Multiprotein Complexes, Mice, Memory, Long-Term, Polymerization, TOR Serine-Threonine Kinases
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