CBP Histone Acetyltransferase Activity Is a Critical Component of Memory Consolidation

Korzus, Edward; Rosenfeld, Michael G.; Mayford, Mark

doi:10.1016/j.neuron.2004.06.002

Cited by 766 publications

(752 citation statements)

References 59 publications

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“…These models are reviewed in [198], and have been analyzed at the molecular level in different learning and memory tasks. Studies examining the effect of a partial or total loss of CBP function show the involvement of its HAT activity in LTP and LTM, and suggest that CBP is not required for the formation of short-term memory (STM) [47,[199][200][201][202]. Nevertheless, another study using a conditional model with complete CBP inactivation in excitatory neurons of the forebrain showed an impairment of both memory types [203].…”

Section: Transgenic Hat Animal Modelsmentioning

confidence: 99%

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

et al. 2013

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The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen longterm events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.

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Section: Transgenic Hat Animal Modelsmentioning

confidence: 99%

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

et al. 2013

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“…Several recent studies have demonstrated that chromatin modification, specifically histone hyperacetylation, plays an important role in the molecular mechanism of learning and formation of a long-term memory in Aplysia and mice [1,12,19,21]. Since associative learning is an integrated component of psychostimulant-induced sensitization [5,37], HDAC inhibitors may potentiate amphetamine-induced behavioral sensitization by enhancing associative learning and memory consolidation.…”

Section: Learning Processes Governing Amphetamine Sensitizationmentioning

confidence: 99%

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

Kalda

Heidmets

Shen

et al. 2007

Behavioural Brain Research

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The behavioral sensitization produced by repeated amphetamine treatment may represent the neural adaptations underlying some of the features of psychosis and addiction in humans. Chromatin modification (specifically histone hyperacetylation) was recently recognized as an important regulator of psychostimulant-induced plasticity. We have investigated the effects of treatment with the histone deacetylase (HDAC) inhibitors butyric acid (BA, 630 mg/kg, i.p) and valproic acid (VPA, 175 mg/kg, i.p.) on the psyhcostimulant locomotor sensitization induced by amphetamine (AMPH, 2.0 mg/kg, i.p.). Neither BA nor VPA had locomotor effects alone, but both significantly potentiated the amphetamine-induced behavioral sensitization in mice. At the molecular level, VPA and amphetamine produced an increase of histone H4 acetylation in the striatum as detected by Western blot analysis, while co-treatment with VPA and AMPH produced an additive effect on histone H4 acetylation. We then administered the HDAC inhibitors after treatment with amphetamine for 8 days to establish locomotor sensitization. We found that repeated administration of VPA or BA for 6 days inhibited the expression of sensitized response following amphetamine challenge. Finally, in a context-specific model we studied the effect of HDAC inhibitors on amphetamine-induced association of the treatment environment (associative learning). We found that VPA and BA enhance the context-specificity of expression of amphetamine sensitization. Thus, HDAC inhibitors differentially modulate the induction and expression of amphetamine-induced effects. Together, these results suggest that dynamic changes in chromatin modification may be an important mechanism underlying amphetamine-induced neuronal plasticity and associative learning.

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“…Recent evidence indicates that regulation of chromatin structure also serves as an additional level of control in this cascade. In particular, memory formation has been shown to be associated with histone acetylation (Alarcon et al, 2004;Guan et al, 2002;Korzus et al, 2004;Levenson et al, 2004;Vecsey et al, 2007;Wood et al, 2005). This process of histone acetylation relaxes chromatin structure, making it more accessible to transcriptional machinery (Lunyak et al, 2002;Turner et al, 2002;Varga-Weisz and Becker, 1998).…”

mentioning

confidence: 99%

DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity

Miller

Campbell

Sweatt

2008

Neurobiology of Learning and Memory

384

359

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A clear understanding is developing concerning the importance of epigenetic-related molecular mechanisms in transcription-dependent long-term memory formation. Chromatin modification, in particular histone acetylation, is associated with transcriptional activation, and acetylation of histone 3 (H3) occurs in Area CA1 of the hippocampus following contextual fear conditioning training. Conversely, DNA methylation is associated with transcriptional repression, but is also dynamically regulated in Area CA1 following training. We recently reported that inhibition of the enzyme responsible for DNA methylation, DNA methyltransferase (DNMT), in the adult rat hippocampus blocks behavioral memory formation. Here we report that DNMT inhibition also blocks the concomitant memory-associated H3 acetylation, without affecting phosphorylation of its upstream regulator, extracellular signal-regulated kinase (ERK). Interestingly, the DNMT inhibitor-induced deficit in memory consolidation, along with deficits in long-term potentiation, can be rescued by pharmacologically increasing levels of histone acetylation prior to DNMT inhibition. These observations suggest that DNMT activity is not only necessary for memory and plasticity, but that DNA methylation may work in concert with histone modifications to regulate plasticity and memory formation in the adult rat hippocampus.

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CBP Histone Acetyltransferase Activity Is a Critical Component of Memory Consolidation

Cited by 766 publications

References 59 publications

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

Acetyltransferases (HATs) as Targets for Neurological Therapeutics

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity

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