The DOI matches its Crossref record; 74 of the 75 references it cites were found in a registry or an index.
Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories
Open accessAbstract
Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CI-994 is an orally active class I HDAC inhibitor that has undergone several phase II/III clinical trials on cancer treatment.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CI-994 can cross the blood–brain barrier and is a cognitive enhancer.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CI-994 is a molecular memory aid and promotes memory formation and cognitive function in vivo [9, 17, 21–24].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CI-994 is an orally bioavailable specific class I HDAC inhibitor which can across the blood–brain barrier [16, 17].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“CI-994 acts as a memory enhancer and alleviates cognitive deficits in mouse models of neurodegenerative disorders [9, 17, 21–24].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measured
The cited source says what the claim attributes to it.
In the citing paper
“CI-994 can cross the blood–brain barrier and is a cognitive enhancer.”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“CI-994 acts as a memory enhancer and alleviates cognitive deficits in mouse models of neurodegenerative disorders [9, 17, 21–24].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [17]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
Langmead, B., Trapnell, C., Pop, M., & Salzberg, S. L. (2009) · Genome Biology · doi:10.1186/gb-2009-10-3-r25 · Cited by 21,849
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,150
Emotional processing of fear: Exposure to corrective information.
Foa, E. B., & Kozak, M. J. (1986) · Psychological Bulletin · doi:10.1037/0033-2909.99.1.20 · Cited by 5,396
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
Differential analysis of gene regulation at transcript resolution with RNA-seq
Trapnell, C., Hendrickson, D. G., Sauvageau, M., Goff, L., Rinn, J. L., & Pachter, L. (2013) · Nature Biotechnology · doi:10.1038/nbt.2450 · Cited by 3,492
Flagged first, then by citations
1 of the 75 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Trapnell, 2013, Differential analysis of gene regulation at transcript resolution with RNA-seq, Nat. Biotechnol., 31, 46, 10.1038/nbt.2450 · DOI · Paper page
- Tsai, 2012, Use of CI-994 and dinaline for the treatment of memory/cognition and anxiety disorders, U.S. patent 8, 563
Cited by
Sorted by citations
Items 301–361 of 361
Zalachoras, I., & Meijer, O. C. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-24493-8_3 · Cited by 1
Woldemichael, B. T., & Mansuy, I. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809324-5.21116-4 · Cited by 1
Effects of cycloheximide on recent and remote appetitive odor discrimination memory in rats
Gotthard, G. H., Bashford, A. R., Bsales, D. A., Golbitz, J.-A., & Shear, R. (2020) · Learning and Motivation · doi:10.1016/j.lmot.2020.101670 · Cited by 1
Okuyama, S., Kotani, M., Ninomiya, F., Sawamoto, A., Fujitani, M., Ano, Y., Kishida, T., Nakajima, M., & Furukawa, Y. (2022) · Nutraceuticals · doi:10.3390/nutraceuticals2020007 · Cited by 1
Electric Shock as Model of Post-Traumatic Stress Disorder in Rodents
Aliczki, M., & Haller, J. (2016) · Springer eBooks · doi:10.1007/978-3-319-08359-9_132 · Cited by 1
Jiang, C., Chen, W., Tao, L., Wang, J., Cheng, K., Zhang, Y., Qi, Z., & Zheng, X. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1090290 · Cited by 1
Engrams of Fear Memory Attenuation
Gräff, J. (2024) · Advances in neurobiology · doi:10.1007/978-3-031-62983-9_9 · Cited by 2
Self-citationHistone Deacetylases as Therapeutic Targets in Neurodegenerative Diseases
Sananbenesi, F., & Fischer, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803239-8.00003-x · Cited by 1
Epigenetics and alcohol use disorders
Sagarkar, S., & Sakharkar, A. J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800226-1.00018-6 · Cited by 2
Caoyang, J., Li, J., Wei, C. H. E. N., Yang, Y., Hu, Y., & Zheng, X. (2019) · Advances in Psychological Science · doi:10.3724/sp.j.1042.2019.00268 · Cited by 1
Novel strategies to cure imprinting disorders
Horsthemke, B., & Zechner, U. (2020) · Medizinische Genetik · doi:10.1515/medgen-2020-2043 · Cited by 1
Epigenetics of Memory Processes
Pulya, S., & Ghosh, B. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91909-8.00018-9 · Cited by 1
Alberini, C. M. (2015) · Journal of the American Psychoanalytic Association · doi:10.1177/0003065115579720 · Cited by 2
Zhu, Z., Wang, Y., Jia, J., Huang, L., Rao, Y., & Wu, Y. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/320101 · Cited by 1
Lancaster, C. L., & Monfils, M. (2015) · Emerging Trends in the Social and Behavioral Sciences · doi:10.1002/9781118900772.etrds0211
Harrison, C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4269
An epigenetic way to forget those painful moments
Diegelmann, S., & Sprecher, S. G. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.03.003
Drug helps to clear traumatic memories
Reardon, S. (2014) · Nature · doi:10.1038/nature.2014.14534
An Epigenetic Approach to Unlearning Old Fears in Animals
Dubovsky, S. L. (2014) · Journal watch · doi:10.1056/nejm-jw.na33697
Oxytocin Receptors and Neurobehavior
Kumsta, R., Zang, J. C. S., & Moser, D. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-29901-3_10
ENGAGING TOUCH & MOVEMENT IN SOMATIC EXPERIENCING ® TRAUMA RESOLUTION APPROACH.
Silva, S. M. G. (2014)
Characterisation of the gene PTPRS in the development of the cerebral cortex
Sherlock, W. T. (2017) · UCL Discovery (University College London)
Epigenetic regulators sculpt the plastic brain
Guan, J., Xie, H. B., & Liu, S. (2017) · Frontiers in Biology · doi:10.1007/s11515-017-1465-z
Dunsmoor, J. E., & Kroes, M. C. W. (2020) · Oxford University Press eBooks · doi:10.1093/oso/9780190881511.003.0006
Абрамец, И. И., Евдокимов, Д. В., Кузнецов, Ю. В., & Сидорова, Ю. В. (2020) · Университетская клиника · doi:10.26435/uc.v0i3(36).559
From mechanical objectivity to narrative turn: how film has inspired science on trauma
Wu, H. Y. (2021) · Journal of Trauma & Dissociation · doi:10.1080/15299732.2021.1925864 · Cited by 1
Technology Early Warnings; A Plethora of Threats and Opportunities
Sharan, Y., Gordon, T. J., & Florescu, E. (2021) · Advanced sciences and technologies for security applications · doi:10.1007/978-3-030-72571-6_11
Li, X., Zhao, Q., Wang, Z., Liau, W., Basic, D., Ren, H., Marshall, P. R., Zajaczkowski, E. L., Leighton, L. J., Madugalle, S. U., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.01.454607
Gräff, J. (2021) · Cerveau & Psycho · doi:10.3917/cerpsy.134.0032
Self-citationHistone Deacetylase Inhibitors
Pandey, S. C. (2014) · Springer eBooks · doi:10.1007/978-3-642-27772-6_394-2
Histone Deacetylase Inhibitors
Pandey, S. C. (2015) · Springer eBooks · doi:10.1007/978-3-642-36172-2_394
Drugs help to dull bad memories
(2014) · Nature · doi:10.1038/505457a
Development of Memory Circuits under Epigenetic Regulation
Guan, J. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108768450.029
(2022) · Cambridge University Press eBooks · doi:10.1017/9781108768450.019
Identification of neuronal ensembles involved in remote fear memory extinction impairmentsPreprint
Tomaszewski, K. F., Łukasiewicz, K., Robacha, M., & Radwańska, K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.17.558133 · Cited by 1
Increase in histone acetylation rescues a weak remote fear memory in rats
Vinarskaya, A. K., Balaban, P. M., & Zuzina, A. B. (2023) · Журнал высшей нервной деятельности им И П Павлова · doi:10.31857/s0044467723060138
Pharmacological HDAC3 inhibition alters memory updating in young and old micePreprint
Smies, C. W., Bellfy, L., Wright, D. S., Bennetts, S. G., Urban, M. W., Brunswick, C. A., Shu, G., & Kwapis, J. L. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.08.593015
Synaptic plasticity and learning and memory
Cooke, S. F., & Chaloner, F. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00044-4
Technologiefrühwarnungen. Eine Fülle von Bedrohungen und Möglichkeiten
Sharan, Y., Gordon, T. J., & Florescu, E. (2025) · Springer eBooks · doi:10.1007/978-3-031-89564-7_11
Small molecular therapeutic targets for neurodegenerative diseases
Rangappa, N., Upadhyay, R., Lakshman, N., Ramasamy, S., Sevanan, M., Justin, A., & Chinnathambi, S. (2025) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2025.10.012
Ibi, D., Ishida, K., Kojima, T., Yoshida, S., Suzuki, A., Suzuki, S., Yasui, M., Shibuya, K., Nakanishi, M., Yamagami, T., et al. (2025) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2025.174131
Electroacupuncture facilitates remote fear memory erasure via promoting perineuronal net degradation
Teng, S.-W., Guo, W.-B., Song, B.-F., He, Y., Wang, K., Gao, S.-B., Li, W., & Chen, Z.-Y. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03789-3 · Cited by 1
Émotions et sommeil paradoxal : étude comportementale, fonctionnelle et anatomique chez la souris
Rosier, M. (2017) · theses.fr (ABES) · doi:10.70675/18fbbb85zbcdcz4c31zabe2zd1d91cdf4659
Role of the thalamic nucleus reuniens in the cortico-hippocampal coupling and memory consolidation
Ferraris, M. (2020) · theses.fr (ABES) · doi:10.70675/3f54f650z6692z45e7z89dfz4cd46a512b83
The role of the serum response factor in the pathogenesis of Huntington's disease
Awada, A. (2021) · theses.fr (ABES) · doi:10.70675/fabef4b5z9d78z440bz99f2z9be7d0814a03
Hippocampo-cortical interaction underlying episodic memory
Bochereau, A. (2020) · theses.fr (ABES) · doi:10.70675/8f206effz0c76z40d0z91e6z15ccb174c9f1
Li, Y.-P., Gong, J., Yang, L., Peng, R.-R., Jin, L., wang, F., Zhao, X., & Wang, L. (2026) · Research Square · doi:10.21203/rs.3.rs-9230899/v1
Lü, W., Caulfield, T. R., Lee, E., Jeevaratnam, S., Wang, N., Bu, G., Kanekiyo, T., & Li, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.30.721954
From survival to silos: CEOs with famine experience and corporate collaborative culture
Tang, C., Tan, L., & Liu, X. (2026) · Research in International Business and Finance · doi:10.1016/j.ribaf.2026.103467
Inhibiting fear memory recall-induced oligodendrogenesis rescues PTSD-like behaviors
Feng, J., Huang, N.-X., Liu, K., Fan, Y.-C., Chen, J., Zhao, Y.-B., Yu, B., Fu, Q.-F., Mei, F., Wang, F., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03688-z
Boulger, S. L., Lerose, D., Adair, E., Papageorgopoulou, M., Zhao, Y., Avot, B., Thomas, M., Nibber, P., Klug, H., Fancy, N. N., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.22.733753 · Cited by 2
Lu, W., Caulfield, T. R., Lee, E., Jeevaratnam, S., Wang, N., Bu, G., Kanekiyo, T., & Li, Y. (2026) · Neurotherapeutics · doi:10.1016/j.neurot.2026.e00974
Anand, A., Sania, A., Singh, S. K., & Bajad, N. G. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06078-2 · Cited by 1
Histone Deacetylase Inhibitors Improve Memory Function and Decrease Neuropathology in APP/PS1 MicePreprint
McClarty, B. M., Monteiro, R., & Dong, H. (2026) · Research Square · doi:10.21203/rs.3.rs-10816126/v1 · Cited by 1
Bioactive Compounds as Putative Molecules of Neuroplasticity: An Epigenetic Perspective
Zhao, F., Bordoni, L., Mao, Y., Cao, J., Gong, F., Hou, W., Li, T., Gabbianelli, R., & Li, K. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6c08366
A Critical Time Window of Neocortex Modulation for Remote Fear Memory in Rats and Humans
Cao, L., Zhang, Y., Liu, X., Li, Z., Lu, T., Deng, J., Zhang, W., Li, P., Lin, X., Feng, S., et al. (2026) · Advanced Science · doi:10.1002/advs.202520707
Epigenetic mechanisms in brain aging and their role in cognitive decline and mental health disorders
Chinn, C., & Wood, M. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00023-2
Metadata
- Authors
- Gräff, J., Joseph, N. F., Horn, M. E., Samiei, A., Meng, J., Seo, J., Rei, D., Bero, A. W., Phan, T. X., Wagner, F., Holson, E., Xu, J., Sun, J., Neve, R. L., Mach, R. H., Haggarty, S. J., & Tsai, L.-H.
- Affiliations
- Broad Institute (US)
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- Washington University in St. Louis (US)
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 1-2
- Pages
- 261-276
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3986862
- OpenAlex
- W2021415039
- Cited by
- 357
- References
- 75
- Citations by year
- 2026: 13 · 2025: 22 · 2024: 21 · 2023: 20 · 2022: 28 · 2021: 27 · 2020: 25 · 2019: 22 · 2018: 45 · 2017: 32 · 2016: 34 · 2015: 32 · 2014: 36
- FWCI
- 22.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute on Aging
- National Institute on Drug Abuse (R01DA028301)
- National Institute of Neurological Disorders and Stroke (NS078839, R03NS090214, R01NS078839)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- memory reconsolidation, HDAC2, S-nitrosylation, histone acetylation, hippocampal plasticity, histone deacetylase inhibitors, anxiety disorders, memory retrieval, synaptic plasticity
- MeSH terms
- Animals, Fear, Hippocampus, Male, Mice, Inbred C57BL, Neuronal Plasticity, Epigenesis, Genetic, Mice, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Memory, Long-Term, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
