Regulation of Histone Acetylation during Memory Formation in the Hippocampus*

By J. Levenson, Kenneth J. O'Riordan, K. Brown, Mimi A. Trinh, D. Molfese, J. Sweatt. Journal of Biological Chemistry, 2004

1,121 citations recorded by the source corpus.

Formation of long term memory begins with the activation of many disparate signaling pathways that ultimately impinge on the cellular mechanisms regulating gene expression. We investigated whether mechanisms regulating chromatin structure were activated during the early stages of long term memory formation in the hippocampus. Specifically, we investigated hippocampal histone acetylation during the initial stages of consolidation of long term association memories in a contextual fear conditioning paradigm. Acetylation of histone H3 in area CA1 of the hippocampus was regulated in contextual fear conditioning, an effect dependent on activation of N-methyl-d-aspartic acid (NMDA) receptors and ERK, and blocked using a behavioral latent inhibition paradigm. Activation of NMDA receptors in area CA1 in vitro increased acetylation of histone H3, and this effect was blocked by inhibition of ERK signaling. Moreover, activation of ERK in area CA1 in vitro through either the protein kinase C or protein kinase A pathways, biochemical events known to be involved in long term memory formation, also increased histone H3 acetylation. Furthermore, we observed that elevating levels of histone acetylation through the use of the histone deacetylase inhibitors trichostatin A or sodium butyrate enhanced induction of long term potentiation at Schaffer-collateral synapses in area CA1 of the hippocampus, a candidate mechanism contributing to long term memory formation in vivo. In concert with our findings in vitro, injection of animals with sodium butyrate prior to contextual fear conditioning enhanced formation of long term memory. These results indicate that histone-associated heterochromatin undergoes changes in structure during the formation of long term memory. Mimicking memory-associated changes in heterochromatin enhances a cellular process thought to underlie long term memory formation, hippocampal long term potentiation, and memory formation itself.

Subfields: Cancer Research, Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/024ef2d192b998c09f3be4c42f3cba7b63e28670

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Citations in the corpus

Metaplasticity: tuning synapses and networks for plasticity (2008, background): “Animals that have been trained on memory tasks show increased histone acetylation in relevant brain regions, and pharmacological inhibition of histone deacetylase promotes the formation of long-term memory and a late phase of LT”
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “BDNF expression, neurogenesis, and neural proliferation in rodents (124–126), as well as facilitation of long-term memory consolidation, were stimulated by sodium butyrate (127).”
Epigenetic mechanisms in memory formation (2005, background): “A recent study has shown that the same processes that lead to the formation of long-term behavioural memories also lead to epigenetic marking of the genom”
How can memories last for days, years, or a lifetime? Proposed mechanisms for maintaining synaptic potentiation and memory (2019, background): “Correspondingly, inhibition of histone deacetylase enhances fear conditioning and LTP (Levenson et al. 2004; Monsey et al. 2011).”
The world of protein acetylation. (2016, background): “In these cases, all changes in histone acetylation occurred in parallel to phosphorylation events and direct activation of the MAPK-ERK-pathway [276,277], indicating a crosstalk between H3K14 acetylation and H3S10 phosphorylation events [272,277].”
Covalent modification of DNA regulates memory formation. (2007, positive): “In vivo, contextual fear conditioning is accompanied by similar increases in acetylation and phosphorylation of H3 within the hippocampus (Levenson et al., 2004a; Chwang et al., 2006).”
Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation (2007, methodology): “Previous studies examining the effects of HDAC inhibitors on memory have used pretraining drug treatment (Alarcon et al., 2004; Korzus et al., 2004; Levenson et al., 2004), and, as a result, it is not known whether HDAC inhibition affects memory by altering acquisition, consolidation, or retrieval.”
EPIGENETIC REGULATION OF BDNF GENE TRANSCRIPTION IN THE CONSOLIDATION OF FEAR MEMORY (2008, methodology): “…can control gene transcription in the nervous system and modulates long-term memory formation (Guan et al., 2002; Alarcón et al., 2004; Korzus et al., 2004; Levenson et al., 2004, 2006; Kumar et al., 2005; Chwang et al., 2006; Bredy et al., 2007; Fischer et al., 2007; Lubin and Sweatt, 2007).”
The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? (2016, methodology): “(2004) also used butyrate for the first time to artificially elevate histone acetylation in the brain during a critical phase of memory formation and found an enhancement of long-term potentiation (LTP) and contextual fear memory (Levenson et al., 2004).”