mTOR signaling: At the crossroads of plasticity, memory and disease

Hoeffer, Charles A.; Klann, Eric

doi:10.1016/j.tins.2009.11.003

Cited by 1,128PI3K/AKT/mTOR signaling in cancerGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

mTOR signaling: At the crossroads of plasticity, memory and disease

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Hoeffer, Charles A., Klann, Eric·2010·Trends in Neurosciences

DOI 10.1016/j.tins.2009.11.003PMC PMC2821969

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Abstract

Mammalian target of rapamycin (mTOR) is a protein kinase involved in translation control and long-lasting synaptic plasticity. mTOR functions as the central component of two multi-protein signaling complexes, mTORC1 and mTORC2, which can be distinguished from each other based on their unique compositions and substrates. Although the majority of evidence linking mTOR function to synaptic plasticity comes from studies utilizing rapamycin, studies in genetically modified mice also suggest that mTOR couples receptors to the translation machinery for establishing long-lasting synaptic changes that are the basis for higher order brain function, including long-term memory. Finally, perturbation of the mTOR signaling cascade appears to be a common pathophysiological feature of human neurological disorders, including mental retardation syndromes and autism spectrum disorders.

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mTORC1-mediated signaling is required for translation of a subset of dendritic proteins.
“The mammalian target of rapamycin complex 1 (mTORC1)-mediated signaling pathway is required for the translation of a subset of dendritic proteins12”
From Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse (2013) · cites this paper as [12]
mTORC1 is implicated in synaptic plasticity and memory processes.
“and is implicated in synaptic plasticity12, 13, as well as in memory processes12.”
From Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse (2013) · cites this paper as [12]
mTOR signaling contributes to protein synthesis required for neuronal survival, development, synaptic plasticity, learning, and memory.
“mTOR signaling, however, contributes to protein synthesis required for neuronal survival, development, synaptic plasticity, learning, and memory (Hoeffer and Klann, 2010)”
From Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits (2014) · cites this paper as Hoeffer and Klann, 2010
mTOR is a serine/threonine kinase that regulates neurogenesis, dendritic spine growth, protein translation initiation, and protein synthesis via phosphorylation of p70S6 kinase and repression of 4E binding proteins.
“Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates neurogenesis, dendritic spine growth, protein translation initiation, and protein synthesis via a phosphorylation of p70S6 kinase and repression of 4E binding proteins (4EBP 173–175).”
From Mechanisms of ketamine action as an antidepressant (2018) · cites this paper as [175]

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A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566 · see citing works
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216 · see citing works
Upstream and downstream of mTOR
Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181 · see citing works
LTP and LTD
Malenka, R. C., & Bear, M. F. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.012 · Cited by 3,968 · see citing works
The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917 · see citing works
mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery.
Kim, D.-H., Sarbassov, D., Ali, S. M., King, J. E., Latek, R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,135 · see citing works
Rictor, a Novel Binding Partner of mTOR, Defines a Rapamycin-Insensitive and Raptor-Independent Pathway that Regulates the Cytoskeleton
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665 · see citing works
Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB
Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,659 · see citing works
Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease
Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · see citing works
Long-Term Potentiation and Memory
Lynch, M. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00014.2003 · Cited by 2,001 · see citing works
Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,837 · see citing works
The Neurobiology of Consolidations, Or, How Stable is the Engram?
Dudai, Y. (2004) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.142050 · Cited by 1,671 · see citing works
Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals that mTORC2 Is Required for Signaling to Akt-FOXO and PKCα, but Not S6K1
Guertin, D. A., Stevens, D. M., Thoreen, C. C., Burds, A. A., Kalaany, N. Y., Moffat, J., Brown, M., Fitzgerald, K. J., & Sabatini, D. M. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.10.007 · Cited by 1,409 · see citing works
SIN1/MIP1 Maintains rictor-mTOR Complex Integrity and Regulates Akt Phosphorylation and Substrate Specificity
Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S. Y., Huang, Q., Qin, J., & Su, B. (2006) · Cell · doi:10.1016/j.cell.2006.08.033 · Cited by 1,407 · see citing works
Altered synaptic plasticity in a mouse model of fragile X mental retardation
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122205699 · Cited by 1,349 · see citing works
Synaptic plasticity, memory and the hippocampus: a neural network approach to causality
Neves, G., Cooke, S. F., & Bliss, T. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2303 · Cited by 1,207 · see citing works
Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40
Haar, E. V., Lee, S.-I., Bandhakavi, S., Griffin, T. J., & Kim, D. (2007) · Nature Cell Biology · doi:10.1038/ncb1547 · Cited by 1,185 · see citing works
Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome
Brown, V., Jin, P., Ceman, S., Darnell, J. C., O'Donnell, W. T., Tenenbaum, S. A., Jin, X., Feng, Y., Wilkinson, K. D., Keene, J. D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00568-2 · Cited by 1,109 · see citing works
Akt1/PKBα Is Required for Normal Growth but Dispensable for Maintenance of Glucose Homeostasis in Mice
Cho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100462200 · Cited by 959 · see citing works
Translational control of long-lasting synaptic plasticity and memory
Costa-Mattioli, M., Sossin, W. S., Klann, E., & Sonenberg, N. (2009) · Neuron · doi:10.1016/j.neuron.2008.10.055 · Cited by 944 · see citing works
Self-citation
Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis
Ehninger, D., Han, S., Shilyansky, C., Zhou, Y., Li, W., Kwiatkowski, D. J., Ramesh, V., & Silva, A. J. (2008) · Nature Medicine · doi:10.1038/nm1788 · Cited by 879 · see citing works
Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations
Butler, M. G., Dasouki, M. J., Zhou, X.-P., Talebizadeh, Z., Brown, M., Takahashi, T. N., Miles, J. H., Wang, C. H., Stratton, R., Pilarski, R., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2004.024646 · Cited by 778 · see citing works
S6K1 −/− / S6K2 −/− Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5′-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 743 · see citing works
A complex interplay between Akt, TSC2 and the two mTOR complexes
Huang, J., & Manning, B. D. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370217 · Cited by 724 · see citing works
mSin1 Is Necessary for Akt/PKB Phosphorylation, and Its Isoforms Define Three Distinct mTORC2s
Frías, M. A., Thoreen, C. C., Jaffe, J. D., Schroder, W. A., Sculley, T. B., Carr, S. A., & Sabatini, D. M. (2006) · Current Biology · doi:10.1016/j.cub.2006.08.001 · Cited by 690 · see citing works
A Genomic Screen of Autism: Evidence for a Multilocus Etiology
Risch, N., Spiker, D., Lotspeich, L., Nouri, N., Hinds, D., Hallmayer, J., Kalaydjieva, L., McCague, P., Dimiceli, S., Pitts, T., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302497 · Cited by 684 · see citing works
Rapamycin blocks the phosphorylation of 4E‐BP1 and inhibits cap‐dependent initiation of translation.
Beretta, L., Gingras, A., Svitkin, Y. V., Hall, M. N., & Sonenberg, N. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00398.x · Cited by 678 · see citing works
Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinase
Shima, H., Pende, M., Chen, Y., Fumagalli, S., THOMAS, G. V., & Kozma, S. C. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6649 · Cited by 636 · see citing works
Characterization of the FKBP·Rapamycin·FRB Ternary Complex
Banaszynski, L. A., Liu, C. W., & Wandless, T. J. (2005) · Journal of the American Chemical Society · doi:10.1021/ja043277y · Cited by 611 · see citing works
The Autistic Neuron: Troubled Translation?
Kelleher, R. J., & Bear, M. F. (2008) · Cell · doi:10.1016/j.cell.2008.10.017 · Cited by 598 · see citing works
Searching for ways out of the autism maze: genetic, epigenetic and environmental clues
Persico, A. M., & Bourgeron, T. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.05.010 · Cited by 575 · see citing works
Phosphorylation of Mammalian Target of Rapamycin (mTOR) at Ser-2448 IsMediated by p70S6 Kinase
Chiang, G. G., & Abraham, R. T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501707200 · Cited by 562 · see citing works
Dysregulation of mTOR signaling in fragile X syndrome
Sharma, A., Hoeffer, C. A., Takayasu, Y., Miyawaki, T., McBride, S. M., Klann, E., & Zukin, R. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3696-09.2010 · Cited by 557 · see citing works
Self-citation
Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression
Hou, L., & Klann, E. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0995-04.2004 · Cited by 527 · see citing works
Self-citation
An expanding role for mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.06.007 · Cited by 519 · see citing works
Autism and tuberous sclerosis
Smalley, S. L., Tanguay, P. E., Smith, M., & Gutierrez, G. (1992) · Journal of Autism and Developmental Disorders · doi:10.1007/bf01048239 · Cited by 518 · see citing works
Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activityPreprint
Yang, Q., Inoki, K., Ikenoue, T., & Guan, K. (2006) · Genes & Development · doi:10.1101/gad.1461206 · Cited by 510 · see citing works
The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C
Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A. S., Gould, C. M., Lowry, C. J., Newton, A. C., Mao, Y., Miao, Q., et al. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.120 · Cited by 508 · see citing works
A Transient, Neuron-Wide Form of CREB-Mediated Long-Term Facilitation Can Be Stabilized at Specific Synapses by Local Protein Synthesis
Casadio, A., Martin, K. C., Giustetto, M., Zhu, H., Chen, M., Bartsch, D., Bailey, C. H., & Kandel, E. R. (1999) · Cell · doi:10.1016/s0092-8674(00)81653-0 · Cited by 503 · see citing works
PRAS40 Regulates mTORC1 Kinase Activity by Functioning as a Direct Inhibitor of Substrate Binding
Wang, L., Harris, T. E., Roth, R. A., & Lawrence, J. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702376200 · Cited by 491 · see citing works
Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway
Scott, P., Brunn, G. J., Kohn, A. D., Roth, R. A., & Lawrence, J. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7772 · Cited by 479 · see citing works
From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome
Bagni, C., & Greenough, W. T. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1667 · Cited by 475 · see citing works
Dynamic Translational and Proteasomal Regulation of Fragile X Mental Retardation Protein Controls mGluR-Dependent Long-Term Depression
Hou, L., Antion, M. D., Hu, D., Spencer, C. M., Paylor, R., & Klann, E. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.005 · Cited by 469 · see citing works
Self-citation
Identification of Protor as a novel Rictor-binding component of mTOR complex-2
Pearce, L. R., Huang, X., Boudeau, J., Pawłowski, R., Wullschleger, S., Deák, M., Ibrahim, A. F. M., Gourlay, R., Magnuson, M. A., & Alessi, D. R. (2007) · Biochemical Journal · doi:10.1042/bj20070540 · Cited by 462 · see citing works
Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
García‐Martínez, J. M., Moran, J., Clarke, R. G., Gray, A., Cosulich, S. C., Chresta, C. M., & Alessi, D. R. (2009) · Biochemical Journal · doi:10.1042/bj20090489 · Cited by 459 · see citing works
The developmental neurobiology of autism spectrum disorder
DiCicco-Bloom, E., Lord, C., Zwaigenbaum, L., Courchesne, E., Dager, S. R., Schmitz, C., Schultz, R. T., Crawley, J., & Young, L. J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1712-06.2006 · Cited by 434 · see citing works
Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12
Shou, W., Aghdasi, B., Armstrong, D. L., Guo, Q., Bao, S., Charng, M., Mathews, L. S., Schneider, M. D., Hamilton, S. L., & Matzuk, M. M. (1998) · Nature · doi:10.1038/35146 · Cited by 431 · see citing works
Biochemical mechanisms for translational regulation in synaptic plasticity
Klann, E., & Dever, T. E. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1557 · Cited by 422 · see citing works
Self-citation
Translational control of hippocampal synaptic plasticity and memory by the eIF2α kinase GCN2
Costa-Mattioli, M., Gobert, D., Harding, H., Herdy, B., Azzi, M., Bruno, M., Bidinosti, M., Mamou, C. B., Marcinkiewicz, E., Yoshida, M., et al. (2005) · Nature · doi:10.1038/nature03897 · Cited by 421 · see citing works
The Pathophysiology of Fragile X Syndrome
Penagarikano, O., Mulle, J. G., & Warren, S. T. (2007) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.8.080706.092249 · Cited by 420 · see citing works
Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1
Dibble, C. C., Asara, J. M., & Manning, B. D. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00735-09 · Cited by 420 · see citing works
Early Infantile Autism
(2008) · Encyclopedia of Special Education · doi:10.1002/9780470373699.speced0723 · Cited by 400 · see citing works
Chemical Induction of mGluR5- and Protein Synthesis–Dependent Long-Term Depression in Hippocampal Area CA1
Huber, K. M., Roder, J., & Bear, M. F. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.86.1.321 · Cited by 390 · see citing works
Multiallelic Disruption of the rictor Gene in Mice Reveals that mTOR Complex 2 Is Essential for Fetal Growth and Viability
Shiota, C., Woo, J., Lindner, J., Shelton, K. D., & Magnuson, M. A. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.08.013 · Cited by 387 · see citing works
Rheb Activates mTOR by Antagonizing Its Endogenous Inhibitor, FKBP38
Bai, X., Ma, D., Liu, A., Shen, X., Wang, Q. J., Liu, Y., & Jiang, Y. (2007) · Science · doi:10.1126/science.1147379 · Cited by 382 · see citing works
Identification of S6 Kinase 1 as a Novel Mammalian Target of Rapamycin (mTOR)-phosphorylating Kinase
Holz, M. K., & Blenis, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504045200 · Cited by 361 · see citing works
Making synaptic plasticity and memory last: mechanisms of translational regulationPreprint
Richter, J. D., & Klann, E. (2009) · Genes & Development · doi:10.1101/gad.1735809 · Cited by 349 · see citing works
Self-citation
Tuberous Sclerosis: from Tubers to mTOR
Kwiatkowski, D. J. (2003) · Annals of Human Genetics · doi:10.1046/j.1469-1809.2003.00012.x · Cited by 340 · see citing works
Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain
Li, X., Alafuzoff, I., Soininen, H., Winblad, B., & Pei, J. (2005) · The FEBS Journal · doi:10.1111/j.1742-4658.2005.04833.x · Cited by 324 · see citing works
The Translation Repressor 4E-BP2 Is Critical for eIF4F Complex Formation, Synaptic Plasticity, and Memory in the Hippocampus
Banko, J., Poulin, F., Hou, L., Demaria, C., Sonenberg, N., & Klann, E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2423-05.2005 · Cited by 317 · see citing works
Self-citation
Time-restricted role for dendritic activation of the mTOR-p70 S6K pathway in the induction of late-phase long-term potentiation in the CA1
Cammalleri, M., Lütjens, R., Berton, F., King, A. R., Simpson, C., Francesconi, W. G., & Sanna, P. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2336098100 · Cited by 301 · see citing works
Metabotropic Receptor-Dependent Long-Term Depression Persists in the Absence of Protein Synthesis in the Mouse Model of Fragile X Syndrome
Nosyreva, E. D., & Huber, K. M. (2006) · Journal of Neurophysiology · doi:10.1152/jn.01316.2005 · Cited by 292 · see citing works
mTOR signaling to translation.
Gingras, A., Raught, B., & Sonenberg, N. (2004) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-642-18930-2_11 · Cited by 287 · see citing works
NOBEL LECTURE: The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses
Kandel, E. R. (2001) · Bioscience Reports · doi:10.1023/a:1014775008533 · Cited by 280 · see citing works
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1
Jacquemont, S., Hagerman, R. J., Hagerman, P. J., & Leehey, M. A. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70676-7 · Cited by 277 · see citing works
Control of Ser2448 Phosphorylation in the Mammalian Target of Rapamycin by Insulin and Skeletal Muscle Load
Reynolds, T., Bodine, S. C., & Lawrence, J. C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201142200 · Cited by 272 · see citing works
Regulation of the aging process by autophagy.
Salminen, A., & Kaarniranta, K. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.03.004 · Cited by 270 · see citing works
Cyclosporin A, FK506 and rapamycin: more than just immunosuppression
Kunz, J., & Hall, M. N. (1993) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(93)90069-y · Cited by 258 · see citing works
Translational Control via the Mammalian Target of Rapamycin Pathway Is Critical for the Formation and Stability of Long-Term Fear Memory in Amygdala Neurons
Parsons, R. G., Gafford, G. M., & Helmstetter, F. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4209-06.2006 · Cited by 251 · see citing works
Cognitive deficits in Tsc1+/−mice in the absence of cerebral lesions and seizures
Goorden, S. M. I., van Woerden, G. M., van der Weerd, L., Cheadle, J. P., & Elgersma, Y. (2007) · Annals of Neurology · doi:10.1002/ana.21317 · Cited by 247 · see citing works
BDNF activates mTOR to regulate GluR1 expression required for memory formation
Slipczuk, L., Bekinschtein, P., Katche, C., Cammarota, M., Izquierdo, I., & Medina, J. H. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006007 · Cited by 246 · see citing works
Regulation of Eukaryotic Initiation Factor 4E by Converging Signaling Pathways during Metabotropic Glutamate Receptor-Dependent Long-Term Depression
Banko, J. L., Hou, L., Poulin, F., Sonenberg, N., & Klann, E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5196-05.2006 · Cited by 245 · see citing works
Self-citation
Local Protein Synthesis Mediates a Rapid Increase in Dendritic Elongation Factor 1A after Induction of Late Long-Term Potentiation
Tsokas, P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0599-05.2005 · Cited by 242 · see citing works
Impaired platelet responses to thrombin and collagen in AKT-1–deficient mice
Chen, J., De, S., Damron, D. S., Chen, W. S., Hay, N., & Byzova, T. V. (2004) · Blood · doi:10.1182/blood-2003-10-3428 · Cited by 238 · see citing works
Removal of FKBP12 Enhances mTOR-Raptor Interactions, LTP, Memory, and Perseverative/Repetitive Behavior
Hoeffer, C. A., Tang, W., Wong, H., Santillan, A., Patterson, R. J., Martinez, L. A., Tejada-Simon, M. V., Paylor, R. E., Hamilton, S. L., & Klann, E. (2008) · Neuron · doi:10.1016/j.neuron.2008.09.037 · Cited by 235 · see citing works
Self-citation
S6K1 Phosphorylates and Regulates Fragile X Mental Retardation Protein (FMRP) with the Neuronal Protein Synthesis-dependent Mammalian Target of Rapamycin (mTOR) Signaling Cascade
Narayanan, U., Nalavadi, V., Nakamoto, M., Thomas, G., Ceman, S., Bassell, G. J., & Warren, S. T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c800055200 · Cited by 216 · see citing works
Autism and tuberous sclerosis
Wiznitzer, M. (2004) · Journal of Child Neurology · doi:10.1177/08830738040190090701 · Cited by 214 · see citing works
TOR regulation of AGC kinases in yeast and mammals
Jacinto, E., & Lorberg, A. (2008) · Biochemical Journal · doi:10.1042/bj20071518 · Cited by 201 · see citing works
The mTOR pathway and its role in human genetic diseases
ROSNER, M., Hanneder, M., Siegel, N., Valli, A., Fuchs, C., & HENGSTSCHLAGER, M. (2008) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2008.06.001 · Cited by 182 · see citing works
Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly
Herman, G. E., Butter, E. M., Enrile, B. G., Pastore, M., Prior, T. W., & Sommer, A. (2007) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31619 · Cited by 160 · see citing works
Metabotropic glutamate receptors are required for the induction of long-term potentiation
Zheng, F., & Gallagher, J. P. (1992) · Neuron · doi:10.1016/0896-6273(92)90231-2 · Cited by 147 · see citing works
Hypomorphic Mutation of PDK1 Suppresses Tumorigenesis in PTEN+/− Mice
Bayascas, J. R., Leslie, N. R., Parsons, R. E., Fleming, S., & Alessi, D. R. (2005) · Current Biology · doi:10.1016/j.cub.2005.08.066 · Cited by 145 · see citing works
Removal of S6K1 and S6K2 leads to divergent alterations in learning, memory, and synaptic plasticityPreprint
Antion, M. D., Merhav, M., Hoeffer, C. A., Reis, G. F., Kozma, S. C., Thomas, G., Schuman, E. M., Rosenblum, K., & Klann, E. (2008) · Learning & Memory · doi:10.1101/lm.661908 · Cited by 138 · see citing works
Self-citation
mTORC1 signalling and mRNA translation
Proud, C. G. (2009) · Biochemical Society Transactions · doi:10.1042/bst0370227 · Cited by 131 · see citing works
Early Infantile Autism
Kanner, L., & Lesser, L. I. (1958) · Pediatric Clinics of North America · doi:10.1016/s0031-3955(16)30693-9 · Cited by 130 · see citing works
A New Pharmacologic Action of CCI-779 Involves FKBP12-Independent Inhibition of mTOR Kinase Activity and Profound Repression of Global Protein Synthesis
Shor, B., Zhang, W., Toral‐Barza, L., Lucas, J., Abraham, R. T., Gibbons, J. J., & Yu, K. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6487 · Cited by 122 · see citing works
Rapamycin‐sensitive signalling in long‐term consolidation of auditory cortex‐dependent memory
Tischmeyer, W., Schicknick, H., Kraus, M., Seidenbecher, C. I., Staak, S., Scheich, H., & Gundelfinger, E. D. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02820.x · Cited by 120 · see citing works
mGluR-Dependent Long-Term Depression Is Associated with Increased Phosphorylation of S6 and Synthesis of Elongation Factor 1A but Remains Expressed in S6K-Deficient Mice
Antion, M., Hou, L., Wong, H., Hoeffer, C. A., & Klann, E. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.00201-08 · Cited by 113 · see citing works
Self-citation
Behavioral alterations in mice lacking the translation repressor 4E-BP2
Banko, J. L., Merhav, M., Stern, E., Sonenberg, N., Rosenblum, K., & Klann, E. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2006.08.012 · Cited by 110 · see citing works
Self-citation
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Xue, Q., Hopkins, B. D., Perruzzi, C. A., Udayakumar, D., Sherris, D., & Benjamin, L. E. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-2058 · Cited by 109 · see citing works
Impaired synaptic plasticity in a rat model of tuberous sclerosis
von der Brelie, C., Waltereit, R., Zhang, L., Beck, H., & Kirschstein, T. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04594.x · Cited by 108 · see citing works
Review: Autophagy in neurodegeneration: firefighter and/or incendiarist?
Rami, A. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2009.01034.x · Cited by 107 · see citing works
Phosphorylation and local presynaptic protein synthesis in calcium- and calcineurin-dependent induction of crayfish long-term facilitation.
Beaumont, V., Zhong, N., Fletcher, R. B., Froemke, R., & Zucker, R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00483-4 · Cited by 105 · see citing works
Isoform specificity of protein kinase Cs in synaptic plasticityPreprint
Sossin, W. S. (2007) · Learning & Memory · doi:10.1101/lm.469707 · Cited by 102 · see citing works
NMDA receptor activation results in PKA‐ and ERK‐dependent Mnk1 activation and increased eIF4E phosphorylation in hippocampal area CA1
Banko, J. L., Hou, L., & Klann, E. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02734.x · Cited by 101 · see citing works
Self-citation
Intracellular Signaling by Akt: Bound to Be Specific
Franke, T. F. (2008) · Science Signaling · doi:10.1126/scisignal.124pe29 · Cited by 101 · see citing works
Dopaminergic Modulation of Auditory Cortex-Dependent Memory Consolidation through mTOR
Schicknick, H., Schott, B. H., Budinger, E., Smalla, K., Riedel, A., Seidenbecher, C. I., Scheich, H., Gundelfinger, E. D., & Tischmeyer, W. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn026 · Cited by 88 · see citing works
1. EARLY INFANTILE AUTISM, 1943-1955
Eisenberg, L., & Kanner, L. (1958) · Psychopathology · doi:10.4159/harvard.9780674367012.c2 · Cited by 83 · see citing works
The Group I Metabotropic Glutamate Receptor Agonist (S)-3,5-Dihydroxyphenylglycine Induces a Novel Form of Depotentiation in the CA1 Region of the Hippocampus
Zho, W.-M., You, J.-L., Huang, C., & Hsu, K. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08838.2002 · Cited by 81 · see citing works
Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein–protein interactions for substrate recognition
Dunlop, E. A., Dodd, K. M., Seymour, L. A., & Tee, A. R. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.02.024 · Cited by 80 · see citing works
Oncogenes on my mind: ERK and MTOR signaling in cognitive diseases
Krab, L. C., Goorden, S. M. I., & Elgersma, Y. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.07.005 · Cited by 76 · see citing works
Serotonin Activates S6 Kinase in a Rapamycin-Sensitive Manner inAplysia Synaptosomes
Khan, A., Pepio, A., & Sossin, W. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00382.2001 · Cited by 71 · see citing works
Protein synthesis in the dendrite
Tang, S. J., & Schuman, E. M. (2002) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2001.0887 · Cited by 69 · see citing works
Biochemical Pathways by Which Serotonin Regulates Translation in the Nervous System of Aplysia
Yanow, S. K., Manseau, F., Hislop, J., Castellucci, V. F., & Sossin, W. S. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70020572.x · Cited by 64 · see citing works
Rapamycin regulates the phosphorylation of rictor
Akçakanat, A., Singh, G., Hung, M., et al. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.151 · Cited by 62 · see citing works
Comparative analysis of calcineurin inhibition by complexes of immunosuppressive drugs with human FK506 binding proteins
Weiwad, M., Edlich, F., Kilka, S., Erdmann, F., Jarczowski, F., Dorn, M., Moutty, M.-C., & Fischer, G. (2006) · Biochemistry · doi:10.1021/bi061616p · Cited by 60 · see citing works
Protected‐Site Phosphorylation of Protein Kinase C in Hippocampal Long‐Term Potentiation
Sweatt, J. D., Atkins, C. M., Johnson, J. E., English, J., Roberson, E. D., Chen, S., Newton, A. C., & Klann, E. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71031075.x · Cited by 57 · see citing works
Self-citation
RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases
Chano, T., Okabe, H., & Hulette, C. M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.06.075 · Cited by 56 · see citing works
Altered excitation‐contraction coupling with skeletal muscle specific FKBP12 deficiency
Tang, W. D., Ingalls, C. P., Durham, W. J., Snider, J., Reid, M. B., Wu, G., Matzuk, M. M., & Hamilton, S. L. (2004) · The FASEB Journal · doi:10.1096/fj.04-1587fje · Cited by 54 · see citing works
mTORC2 Caught in a SINful Akt
Polak, P., & Hall, M. N. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.09.005 · Cited by 50 · see citing works
5‐HT stimulates eEF2 dephosphorylation in a rapamycin‐sensitive manner in Aplysia neurites
Carroll, M., Warren, O. U., Fan, X., & Sossin, W. S. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02634.x · Cited by 48 · see citing works
The FRB Domain of mTOR: NMR Solution Structure and Inhibitor Design ,
Leone, M., Crowell, K. J., Chen, J., et al. (2006) · Biochemistry · doi:10.1021/bi060976+ · Cited by 48 · see citing works
What controls TOR?
Jacinto, E. (2008) · IUBMB Life · doi:10.1002/iub.56 · Cited by 43 · see citing works
Can Autism Speak to Neuroscience?
Moldin, S. O., Rubenstein, J. L. R., & Hyman, S. E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1944-06.2006 · Cited by 42 · see citing works
PTEN Regulation, a Novel Function for the p85 Subunit of Phosphoinositide 3-Kinase
Barber, D. F., Alvarado-Kristensson, M., González-Garcı́a, A., Pulido, R., & Carrera, A. C. (2006) · Science s STKE · doi:10.1126/stke.3622006pe49 · Cited by 38 · see citing works
PRR5 encodes a conserved proline-rich protein predominant in kidney: analysis of genomic organization, expression, and mutation status in breast and colorectal carcinomas
Johnstone, C. N., Castellvı́-Bel, S., Chang, L. M., et al. (2004) · Genomics · doi:10.1016/j.ygeno.2004.11.002 · Cited by 33 · see citing works
Effects of cyclosporin A, FK506 and rapamycin on calcineurin phosphatase activity in mouse brain
Yu, D., Luo, J., Bu, F., et al. (2006) · IUBMB Life · doi:10.1080/15216540600791555 · Cited by 23 · see citing works

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mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants
Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016) · Nature Medicine · doi:10.1038/nm.4050 · Cited by 1,750 · see citing works
Synaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651 · see citing works
Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy
Millan, M. J., Agid, Y., Brüne, M., Bullmore, E. T., Carter, C. S., Clayton, N. S., Connor, R., Davis, S., Deakin, B., DeRubeis, R. J., et al. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3628 · Cited by 1,292 · see citing works
Psychedelics promote structural and functional neural plasticity
Ly, C., Greb, A. C., Cameron, L. P., Wong, J. M., Barragan, E. V., Wilson, P. C., Burbach, K. F., Soltanzadeh Zarandi, S., Sood, A., Paddy, M. R., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.05.022 · Cited by 1,207 · see citing works
Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits
Tang, G., Gudsnuk, K., Kuo, S.-H., Cotrina, M. L., Rosoklija, G., Sosunov, A., Sonders, M. S., Kanter, E., Castagna, C., Yamamoto, A., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.040 · Cited by 1,146 · see citing works
Mechanisms of ketamine action as an antidepressant
Zanos, P., & Gould, T. D. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.255 · Cited by 1,127 · see citing works
Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure
Li, N., Liu, R.-J., Dwyer, J. M., Banasr, M., Lee, B., Son, H., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.015 · Cited by 1,082 · see citing works
Exercise and mental health
Mikkelsen, K., Stojanovska, L., Polenakovic, M., Bosevski, M., & Apostolopoulos, V. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.09.003 · Cited by 1,072 · see citing works
Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks
Magnuson, B., Ekim, B., & Fingar, D. C. (2012) · Biochemical Journal · doi:10.1042/bj20110892 · Cited by 1,015 · see citing works
The chronic mild stress (CMS) model of depression: History, evaluation and usage
Willner, P. (2017) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.08.002 · Cited by 959 · see citing works
Neurodevelopmental model of schizophrenia: update 2012
Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.23 · Cited by 790 · see citing works
Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents
Duman, R. S., & Voleti, B. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.004 · Cited by 714 · see citing works
Mutations causing syndromic autism define an axis of synaptic pathophysiology
Auerbach, B. D., Osterweil, E. K., & Bear, M. F. (2011) · Nature · doi:10.1038/nature10658 · Cited by 592 · see citing works
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593 · see citing works
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Duman, R. S., Li, N., Liu, R.-J., Duric, V., & Aghajanian, G. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.044 · Cited by 537 · see citing works
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Fries, G. R., Saldana, V. A., Finnstein, J., & Rein, T. (2023) · Molecular Psychiatry · doi:10.1038/s41380-022-01806-1 · Cited by 504 · see citing works
The translation of translational control by FMRP: therapeutic targets for FXS
Darnell, J. C., & Klann, E. (2013) · Nature Neuroscience · doi:10.1038/nn.3379 · Cited by 491 · see citing works
Self-citation
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Dazert, E., & Hall, M. N. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.09.003 · Cited by 460 · see citing works
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Jernigan, C. S., Goswami, D. B., Austin, M. C., Iyo, A. H., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.05.010 · Cited by 386 · see citing works
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Miller, O. H., Yang, L., Wang, C.-C., Hargroder, E. A., Zhang, Y., Delpire, E., & Hall, B. J. (2014) · eLife · doi:10.7554/elife.03581 · Cited by 358 · see citing works
Genetic Removal of p70 S6 Kinase 1 Corrects Molecular, Synaptic, and Behavioral Phenotypes in Fragile X Syndrome Mice
Bhattacharya, A., Kaphzan, H., Alvarez-Dieppa, A. C., Murphy, J. P., Pierre, P., & Klann, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.022 · Cited by 316 · see citing works
Self-citation
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Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
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Richter, J. D., Bassell, G. J., & Klann, E. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4001 · Cited by 275 · see citing works
Self-citation
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Browne, C. A., & Lucki, I. (2013) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00161 · Cited by 285 · see citing works
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Shehata, M., Matsumura, H., Okubo-Suzuki, R., Ohkawa, N., & Inokuchi, K. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4533-11.2012 · Cited by 285 · see citing works
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Ota, K. T., Liu, R.-J., Voleti, B., Maldonado-Aviles, J. G., Duric, V., Iwata, M., Dutheil, S., Duman, C., Boikess, S., Lewis, D. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3513 · Cited by 267 · see citing works
Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses
Busquets-Garcia, A., Puighermanal, E., Pastor, A., de la Torre, R., Maldonado, R., & Ozaita, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.022 · Cited by 273 · see citing works
Spine synapse remodeling in the pathophysiology and treatment of depression
Duman, C. H., & Duman, R. S. (2015) · Neuroscience Letters · doi:10.1016/j.neulet.2015.01.022 · Cited by 257 · see citing works
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Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease
Ma, T., Hoeffer, C. A., Capetillo-Zarate, E., Yu, F., Wong, H., Lin, M. T., Tampellini, D., Klann, E., Blitzer, R. D., & Gouras, G. K. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012845 · Cited by 262 · see citing works
Self-citation
Psychoplastogens: A promising class of plasticity-promoting neurotherapeutics
Olson, D. E. (2018) · Journal of Experimental Neuroscience · doi:10.1177/1179069518800508 · Cited by 257 · see citing works
GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine
Liu, R.-J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.128 · Cited by 256 · see citing works
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Busquets-Garcia, A., Gomis-González, M., Guegan, T., Agustín-Pavón, C., Pastor, A., Mato, S., Pérez-Samartín, A., Matute, C., de la Torre, R., Dierssen, M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3127 · Cited by 241 · see citing works
Selective pharmacogenetic inhibition of mammalian target of Rapamycin complex I (mTORC1) blocks long-term synaptic plasticity and memory storage
Stoica, L., Zhu, P. J., Huang, W., Zhou, H., Kozma, S. C., & Costa-Mattioli, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014715108 · Cited by 232 · see citing works
An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy
Millan, M. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.11.015 · Cited by 229 · see citing works
Restoring Mood Balance in Depression: Ketamine Reverses Deficit in Dopamine-Dependent Synaptic Plasticity
Belujon, P., & Grace, A. A. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.014 · Cited by 225 · see citing works
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Duman, R. S. (2014) · Depression and Anxiety · doi:10.1002/da.22227 · Cited by 213 · see citing works
Inhibition of AMP-activated protein kinase signaling alleviates impairments in hippocampal synaptic plasticity induced by amyloid β
Ma, T., Chen, Y., Vingtdeux, V., Zhao, H., Viollet, B., Marambaud, P., & Klann, E. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1694-14.2014 · Cited by 191 · see citing works
Self-citation
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Iadarola, N. D., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Ballard, E. D., Lundin, N. B., Nugent, A. C., Machado-Vieira, R., & Zarate, C. A. (2015) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622315579059 · Cited by 201 · see citing works
Cell atrophy and loss in depression: reversal by antidepressant treatment
Banasr, M., Dwyer, J. M., & Duman, R. S. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.09.002 · Cited by 201 · see citing works
Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons
Descalzi, G., Gao, V., Steinman, M. Q., Suzuki, A., & Alberini, C. M. (2019) · Communications Biology · doi:10.1038/s42003-019-0495-2 · Cited by 188 · see citing works
Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism
Huber, K. M., Klann, E., Costa-Mattioli, M., & Zukin, R. S. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2656-15.2015 · Cited by 167 · see citing works
Self-citation
Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse
Barak, S., Liu, F., Hamida, S. B., Yowell, Q. V., Neasta, J., Kharazia, V., Janak, P. H., & Ron, D. (2013) · Nature Neuroscience · doi:10.1038/nn.3439 · Cited by 172 · see citing works
Molecular mechanisms underlying alcohol-drinking behaviours
Ron, D., & Barak, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.85 · Cited by 165 · see citing works
A Critical Role for GluN2B-Containing NMDA Receptors in Cortical Development and Function
Wang, C.-C., Held, R. G., Chang, S.-C., Yang, L., Delpire, E., Ghosh, A., & Hall, B. J. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.023 · Cited by 180 · see citing works
Convergent Mechanisms Underlying Rapid Antidepressant Action
Zanos, P., Thompson, S. M., Duman, R. S., Zarate, C. A., & Gould, T. D. (2018) · CNS Drugs · doi:10.1007/s40263-018-0492-x · Cited by 171 · see citing works
Protein Synthesis during Sleep Consolidates Cortical Plasticity In Vivo
Seibt, J., Dumoulin, M. C., Aton, S. J., Coleman, T., Watson, A., Naidoo, N., & Frank, M. G. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.016 · Cited by 162 · see citing works
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Woo, E., Sansing, L. H., Arnsten, A. F. T., & Datta, D. (2021) · Chronic Stress · doi:10.1177/24705470211029254 · Cited by 159 · see citing works
Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression
Licznerski, P., & Duman, R. S. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.09.057 · Cited by 157 · see citing works
Obesity-driven synaptic remodeling affects endocannabinoid control of orexinergic neurons
Cristino, L., Busetto, G., Imperatore, R., Ferrandino, I., Palomba, L., Silvestri, C., Petrosino, S., Orlando, P., Bentivoglio, M., Mackie, K., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219485110 · Cited by 143 · see citing works
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Self-citation
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Fortin, D. A., Srivastava, T., Dwarakanath, D., Pierre, P., Nygaard, S., Derkach, V. A., & Soderling, T. R. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.6034-11.2012 · Cited by 120 · see citing works
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Gafford, G. M., Parsons, R. G., & Helmstetter, F. J. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.023 · Cited by 110 · see citing works
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Nicolini, C., Ahn, Y., Michalski, B., Rho, J. M., & Fahnestock, M. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0184-4 · Cited by 109 · see citing works
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Dello Russo, C., Lisi, L., Feinstein, D. L., & Navarra, P. (2013) · Glia · doi:10.1002/glia.22433 · Cited by 96 · see citing works
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Carlyle, B. C., Duque, A., Kitchen, R. R., Bordner, K. A., Coman, D., Doolittle, E., Papademetris, X., Hyder, F., Taylor, J. R., & Simen, A. A. (2012) · Development and Psychopathology · doi:10.1017/s095457941200079x · Cited by 80 · see citing works
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Ma, T. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15541 · Cited by 55 · see citing works
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Sengupta, S., Giaime, E., Narayan, S., Hahm, S., Howell, J., O’Neill, D., Vlasuk, G. P., & Saiah, E. (2019) · Scientific Reports · doi:10.1038/s41598-019-40693-5 · Cited by 72 · see citing works
Retinal ganglion cell dendrite pathology and synapse loss
Agostinone, J., & Di Polo, A. (2015) · Progress in Brain Research · doi:10.1016/bs.pbr.2015.04.012 · Cited by 68 · see citing works
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Jobim, P. F. C., Pedroso, T. R., Werenicz, A., Christoff, R. R., Maurmann, N., Reolon, G. K., Schröder, N., & Roesler, R. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.12.004 · Cited by 68 · see citing works
REDD2-mediated inhibition of mTOR promotes dendrite retraction induced by axonal injury
Morquette, B., Morquette, P., Agostinone, J., Feinstein, E., McKinney, R. A., Kolta, A., & Di Polo, A. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.149 · Cited by 60 · see citing works
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Hepgul, N., Cattaneo, A., Agarwal, K., Baraldi, S., Borsini, A., Bufalino, C., Forton, D. M., Mondelli, V., Nikkheslat, N., Lopizzo, N., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.50 · Cited by 62 · see citing works
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Lee, H.-K., Kwon, B., Lemere, C. A., de la Monte, S., Itamura, K., Ha, A. Y., & Querfurth, H. W. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-161029 · Cited by 57 · see citing works
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Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation
Hoffman, A. N., Parga, A., Paode, P. R., Watterson, L. R., Nikulina, E. M., Hammer, R. P., & Conrad, C. D. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.02.004 · Cited by 45 · see citing works
Defects in translational regulation contributing to human cognitive and behavioral disease
Darnell, J. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2011.05.002 · Cited by 43 · see citing works
Coupling between Nutrient Availability and Thyroid Hormone Activation
Lartey, L. J., Werneck-de-Castro, J. P., O-Sullivan, I., Unterman, T. G., & Bianco, A. C. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.665505 · Cited by 41 · see citing works
Ketamine prevents stress-induced cognitive inflexibility in rats
Nikiforuk, A., & Popik, P. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.11.009 · Cited by 39 · see citing works
Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation
Almeida-Filho, D. G., Queiroz, C. M., & Ribeiro, S. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2886-9 · Cited by 38 · see citing works
Analysis of proteins that rapidly change upon mechanistic/mammalian target of rapamycin complex 1 (mTORC1) repression identifies parkinson protein 7 (PARK7) as a novel protein aberrantly expressed in tuberous sclerosis complex (TSC)
Niere, F., Namjoshi, S., Song, E., Dilly, G. A., Schoenhard, G., Zemelman, B. V., Mechref, Y., & Raab-Graham, K. F. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.055079 · Cited by 38 · see citing works
“Thus, many theorize that diseases with overactive mTORC1 arise from excessive protein synthesis (14).”
Background
mTORC1 inhibitor effects on rapid ketamine-induced reductions in suicidal ideation in patients with treatment-resistant depression
Averill, L. A., Averill, C. L., Gueorguieva, R., Fouda, S., Sherif, M., Ahn, K.-H., Ranganathan, M., D'Souza, D. C., Southwick, S. M., Sanacora, G., et al. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.01.104 · Cited by 33 · see citing works
Glucagon-Like Peptide-2 Receptor is Involved in Spatial Cognitive Dysfunction in Rats After Chronic Cerebral Hypoperfusion
Xie, Y.-C., Yao, Z.-H., Yao, X.-L., Pan, J.-Z., Zhang, S.-F., Zhang, Y., & Hu, J.-C. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180782 · Cited by 24 · see citing works
The integral role of PTEN in brain function: from neurogenesis to synaptic plasticity and social behavior
Chwin, N., & Kiryk, A. (2024) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2024-2657 · Cited by 3 · see citing works

Growing knowledge of the mTOR signaling network
Huang, K., & Fingar, D. C. (2014) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2014.09.011 · Cited by 301 · see citing works
mTOR-Dependent Cell Survival MechanismsPreprint
Hung, C., García-Haro, L., Sparks, C. A., & Guertin, D. A. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008771 · Cited by 205 · see citing works
Regulation and metabolic functions of mTORC1 and mTORC2.
Szwed, A., Kim, E., & Jacinto, E. (2021) · Physiological Reviews · doi:10.1152/physrev.00026.2020 · Cited by 723 · see citing works
Dynamic modelling of the PI3K/MTOR signalling network uncovers biphasic dependence of mTORC1 activity on the mTORC2 subunit SIN1
Ghomlaghi, M., Shin, S., Yang, G., James, D. E., & Nguyen, L. K. (2021) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008513 · Cited by 24 · see citing works
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
Apelo, S. I. A., & Lamming, D. W. (2016) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw090 · Cited by 240 · see citing works

Authors: Hoeffer, C. A., & Klann, E.
Affiliations: New York University (US)
Corresponding author: Klann, Eric
ORCID: Hoeffer, Charles A.
Klann, Eric
Venue: Trends in Neurosciences
Publisher: Elsevier BV
Published: 2010-02
Volume: 33
Issue: 2
Pages: 67-75
ISSN: 0166-2236 (ISSN-L)
DOI: 10.1016/j.tins.2009.11.003
PMC: PMC2821969
OpenAlex: W2086236919
Cited by: 1,128
References: 117
Citations by year: 2026: 35 · 2025: 57 · 2024: 46 · 2023: 48 · 2022: 75 · 2021: 74 · 2020: 74 · 2019: 51 · 2018: 75 · 2017: 58 · 2016: 95 · 2015: 100 · 2014: 94 · 2013: 84 · 2012: 79
FWCI: 3.97
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Neurosciences (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS034007, R01NS047384)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: mTOR signaling, mTORC1, mTORC2, synaptic plasticity, long-term memory, translational regulation, rapamycin, neurological disorders, intellectual disability, autism spectrum disorder
MeSH terms: Animals, Gene Expression Regulation, Humans, Memory, Models, Biological, Nervous System Diseases, Neuronal Plasticity, Signal Transduction, Protein Serine-Threonine Kinases, Intracellular Signaling Peptides and Proteins, Mice, TOR Serine-Threonine Kinases

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mTOR signaling: At the crossroads of plasticity, memory and disease

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