ArticleProceedings of the National Academy of Sciences of the United States of America2022
The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- HDAC3 Inhibitor RGFP966 Enhances Memory Persistence in a Biphasic Manner and Modulates NF-kB Nuclear Localization.Molecular neurobiology · 2026Article
- HDAC inhibitor treatment restores transcriptome, chromatin accessibility, and memory deficits in a mouse model for Down syndrome.iScience · 2026Article
- Histone Deacetylase Inhibitors Improve Memory Function and Decrease Neuropathology in APP/PS1 Mice.Research square · 2026Article
- The HDAC inhibitor sodium butyrate moderately enhances long-term fear extinction memory retrieval in humans.Molecular psychiatry · 2026Article
- A computational framework for epigenetic plasticity in memory.Brain : a journal of neurology · 2026Review
- Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2026Article
- Bridging neurobiological mechanisms and translational applications in cognitive science: inspirations from the MCCS-NYUAD meeting 2025.Molecular brain · 2026Review
- CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Epigenetic manipulation of anterior insular cortex alters neural signals and cognitive control.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Cell-type- and locus-specific epigenetic editing of memory expression.Nature genetics · 2025Article
- Manipulating Engram Histone Acetylation Alters Memory Consolidation.Hippocampus · 2025Article
- Gut Microbiota and Obsessive-Compulsive Disorder: A Systematic Review of Mechanistic Links, Evidence from Human and Preclinical Studies, and Therapeutic Prospects.Life (Basel, Switzerland) · 2025Review
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- Hitting Two Birds With One Stone: Dual Modulation of Brain Carbonic Anhydrases and Histone Deacetylases Boosts Memory Consolidation.Archiv der Pharmazie · 2025Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Class 1 histone deacetylases differentially modulate memory and synaptic genes in a spatial and temporal manner in aged and APP/PS1 mice.Brain research · 2024Article
- Research progress on intestinal microbiota regulating cognitive function through the gut-brain axis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- High-throughput sensitive screening of small molecule modulators of microexon alternative splicing using dual Nano and Firefly luciferase reporters.Nature communications · 2024Article
- Optimizing in silico drug discovery: simulation of connected differential expression signatures and applications to benchmarking.Briefings in bioinformatics · 2024Article
- Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.Psychopharmacology · 2024Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Long-term memory formation relies on synaptic plasticity, neuronal activity-dependent gene transcription, and epigenetic modifications. Multiple studies have shown that HDAC inhibitor (HDACi) treatments can enhance individual aspects of these processes and thereby act as putative cognitive enhancers. However, their mode of action is not fully understood. In particular, it is unclear how systemic application of HDACis, which are devoid of substrate specificity, can target pathways that promote memory formation. In this study, we explore the electrophysiological, transcriptional, and epigenetic responses that are induced by CI-994, a class I HDACi, combined with contextual fear conditioning (CFC) in mice. We show that CI-994–mediated improvement of memory formation is accompanied by enhanced long-term potentiation in the hippocampus, a brain region recruited by CFC, but not in the striatum, a brain region not primarily implicated in fear learning. Furthermore, using a combination of bulk and single-cell RNA-sequencing, we find that, when paired with CFC, HDACi treatment engages synaptic plasticity-promoting gene expression more strongly in the hippocampus, specifically in the dentate gyrus (DG). Finally, using chromatin immunoprecipitation-sequencing (ChIP-seq) of DG neurons, we show that the combined action of HDACi application and conditioning is required to elicit enhancer histone acetylation in pathways that underlie improved memory performance. Together, these results indicate that systemic HDACi administration amplifies brain region-specific processes that are naturally induced by learning.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.