Consolidation of an aversive taste memory requires two rounds of transcriptional and epigenetic regulation in the insular cortex

doi:10.1016/j.bbr.2018.09.009

Behavioural Brain Research

Volume 356, 1 January 2019, Pages 371-374

https://doi.org/10.1016/j.bbr.2018.09.009 Get rights and content

Highlights

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CTA-memory consolidation requires synthesis of new mRNA in the IC immediately and 7 h after acquisition of this task.
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Inhibition of class I-type HDAC in the IC, immediately and 7 h after acquisition, converts a weak CTA into a strong one.
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Memory consolidation of a strong CTA is not improved by the inhibition of class I-type HDAC in the IC.

Abstract

The current view of the neurobiology of learning and memory suggests that long-term memory (LTM) depends not only on the de novo protein synthesis but also on the synthesis of mRNA even hours after the acquisition of memory, as well as that the regulation of transcription through the histone acetylation is essential for the memory establishment. Our previous studies showed that protein synthesis inhibition around the time of training and 5–7 hours after acquisition in the insular cortex (IC) prevents the consolidation of conditioned taste aversion (CTA), a well-established learning and memory paradigm in which an animal learns to associate a novel taste with nausea. However, the participation of mRNA synthesis and the epigenetic regulation through histone acetylation in this process remains unexplored. In the present study we evaluated the effect of the inhibition of transcription as well as deacetylation of histones at two temporal windows on the consolidation of CTA. Thus, immediately or seven hours after CTA acquisition animals received a microinfusion of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) or MS-275 in the IC, respectively. The present results show that transcription inhibition immediately and 7 h after acquisition impairs the CTA memory consolidation, whereas the inhibition of histone deacetylation strengths this memory at those temporal windows. These findings reveal that CTA memory requires recurrent rounds of transcriptional modulation events in the IC in order to consolidate this memory trace, demonstrating that transcriptional and epigenetic modulation substantially contribute to memory-consolidation-related functions performed by a neocortical area even several hours after memory acquisition.

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Acknowledgements

This research was supported by PAPIITIN215816.

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Cited by (5)

Epigenetic mechanisms regulate cue memory underlying discriminative behavior
2022, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
A 2014 study by Nuñez-Jaramillo and colleagues (Núñez-Jaramillo et al., 2014) found that infusing the general class I HDAC inhibitor, sodium butyrate (NaB), in the IC during CTA strengthened the associative memory between the taste cue and malaise, which was revealed behaviorally as delayed extinction of the taste aversion. The same effect of HDAC inhibition on CTA memory was also reported by (Rodríguez-Blanco et al., 2019) with post-training IC injections of the HDAC1/3-selective inhibitor MS-275 (“entinostat”). In this study, the authors determined that at least two rounds of transcription – one immediately, and one 7 h after CTA acquisition – were needed to strengthen CTA memory consolidation for a specific flavor.
The burgeoning field of neuroepigenetics has introduced chromatin modification as an important interface between experience and brain function. For example, epigenetic mechanisms like histone acetylation and DNA methylation operate throughout a lifetime to powerfully regulate gene expression in the brain that is required for experiences to be transformed into long-term memories. This review highlights emerging evidence from sensory models of memory that converge on the premise that epigenetic regulation of activity-dependent transcription in the sensory brain facilitates highly precise memory recall. Chromatin modifications may be key for neurophysiological responses to transient sensory cue features experienced in the “here and now” to be recapitulated over the long term. We conclude that the function of epigenetic control of sensory system neuroplasticity is to regulate the amount and type of sensory information retained in long-term memories by regulating neural representations of behaviorally relevant cues that guide behavior. This is of broad importance in the neuroscience field because there are few circumstances in which behavioral acts are devoid of an initiating sensory experience.
Artificial taste avoidance memory induced by coactivation of NMDA and β-adrenergic receptors in the amygdala
2019, Behavioural Brain Research
Citation Excerpt :
All these processes culminate in the increase in protein synthesis required for neuronal remodeling within the neural networks necessary to acquire and consolidate taste avoidance memories [37]. In this regard, it has been proposed that a single molecular event triggered during acquisition may not be sufficient to maintain long-term memory; and the persistence of memory requires rounds of consolidation-like processes during different time windows [38–41]. Therefore, we suggest that emulation of US amygdalar events is necessary to initiate the molecular pathways involved in modifications of the amygdala-insular network and the coactivation of NMDA and β-adrenergic receptors during the post-learning period facilitates the taste avoidance memory consolidation through protein synthesis-dependent mechanisms.
The association between a taste and gastric malaise allows animals to avoid the ingestion of potentially toxic food. This association has been termed conditioned taste aversion (CTA) and relies on the activity of key brain structures such as the amygdala and the insular cortex.
The establishment of this gustatory-avoidance memory is related to glutamatergic and noradrenergic activity within the amygdala during two crucial events: gastric malaise (unconditioned stimulus, US) and the post-acquisition spontaneous activity related to the association of both stimuli. To understand the functional implications of these neurochemical changes on avoidance memory formation, we assessed the effects of pharmacological stimulation of β-adrenergic and glutamatergic NMDA receptors through the administration of a mixture of L-homocysteic acid and isoproterenol into the amygdala after saccharin exposure on specific times to emulate the US and post-acquisition local signals that would be occurring naturally under CTA training. Our results show that activation of NMDA and β-adrenergic receptors generated a long-term avoidance response to saccharin, like a naturally induced rejection with LiCl. Moreover, the behavioral outcome was accompanied by changes in glutamate, norepinephrine and dopamine levels within the insular cortex, analogous to those displayed during memory retrieval of taste aversion memory. Therefore, we suggest that taste avoidance memory can be induced artificially through the emulation of specific amygdalar neurochemical signals, promoting changes in the amygdala-insular cortex circuit enabling memory establishment.
Trichostatin a inhibits phenotypic transition and induces apoptosis of the TAF-treated normal colonic epithelial cells through regulation of TGF-β pathway
2019, International Journal of Biochemistry and Cell Biology
Citation Excerpt :
Post-translational modifications of histones play an important role in transcriptional regulation (Nakamura et al., 2018; Hatakeyama et al., 2018). Acetylation and deacetylation of histone tails, respectively mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC), regulate gene activation and repression (Kelly et al., 2018; Rodríguez-Blanco et al., 2019). Cumulative evidence suggests aberrant HAT and HDAC activities in several cancer cells (Yu et al., 2018; Shanmugam et al., 2017).
Tumor-associated fibroblasts (TAFs) contribute to transdifferentiation of stromal cells in tumor microenvironment. Epithelial-mesenchymal transition (EMT) is a procedure of phenotypic remodeling of epithelial cells and extensively exists in local tumoral stroma. Histone deacetylase (HDAC) inhibitor Tricostatin A (TSA) and sodium butyrate (SB) are reported to play important roles in the regulation of biological behaviour of cancer cells. However, whether TSA or SB is involved in control of EMT in colon epithelial cells induced by TAFs remains unidentified. In present study, we used conditioned medium (CM) form TAF-like CCD-18Co cells to stimulate 2D- and 3D-cultured colon epithelial HCoEpiC cells for 24 h and 4 d. We found that the CCD-18Co CM triggered multiple morphological changes in HCoEpiCs including prolonged cell diameters, down-regulation of E-cadherin and up-regulation of vimentin and α-SMA. Besides, ZEB1 and Snail expression and migration were also promoted by the CM. These phenomena were abolised by 5 μg/ml LY364947, a TGF-β receptor inhibitor. CCD-18Co induced up-regulation of HDAC1 and HDAC2 in the 2D and 3D models, while no change of HDAC4 exprerssion was found. Treatment of 2 μg/ml TSA reversed the CCD-18Co-induced morphological changes and migration of the HCoEpiCs, and suppressed the downregulation of E-cadherin and upregulation of vimentin, α-SMA, ZEB1 and Snail. However, the suppressive effect of 4 mg/ml SB on the EMT was not observed. TSA down-regulated the expressions of Smad2/3, p-Smad2/3 amd HDAC4. Besides, TSA promoted the apoptosis rate (36.84 ± 6.52%) comparing with the CCD-18Co-treated HCoEpiCs (3.52 ± 0.85%, P < 0.05), with promotion of Bax (0.5893±0.0498 in 2D and 0.8867±0.0916 in 3D) and reduction of Bcl-2 (0.0476±0.0053 in 2D and 0.0294±0.0075 in 3D). TSA stimulated expression of phosphorylated-p38 MAPK in 2D (0.3472±0.0249) and 3D (0.3188±0.0248). After pre-treatment with p38 MAPK inhibitor VX-702 (0.5 mg/ml), the apoptosis rate of TSA was decreased in 2D (10.32%) and 3D (5.26%). Our observations demonstrate that epigenetic treatment with HDAC inhibitor TSA may be a useful therapeutic tool for the reversion of TAF-induced EMT in colon epithelium through mediating canonical Smads pathway and non-canonical p38 MAPK signalling.
A time-dependent role for the transcription factor CREB in neuronal allocation to an engram underlying a fear memory revealed using a novel in vivo optogenetic tool to modulate CREB function
2020, Neuropsychopharmacology
Activity of insula to basolateral amygdala projecting neurons is necessary and sufficient for taste valence representation
2019, Journal of Neuroscience

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Short communicationConsolidation of an aversive taste memory requires two rounds of transcriptional and epigenetic regulation in the insular cortex

Highlights

Abstract

Section snippets

Acknowledgements

Behav. Brain Res.

Neurobiol. Learn. Mem.

Neuron

Curr. Biol.

J. Biol. Chem.

Neurobiol. Learn. Mem.

Behavioural Brain Res. SreeTestContent1

Neuropharmacology

The regulation of transcription in memory consolidation

Cold Spring Harb. Perspect. Biol.

Late protein synthesis dependent phases in CTA long-term memory: BDNF requirement

Front. Behav. Neurosci.

Two time periods of hippocampal mRNA synthesis are required for memory consolidation of fear-motivated learning

J. Neurosci.

De novo mRNA synthesis is required for both consolidation and reconsolidation of fear memories in the amygdala

Learn. Mem.

Short communication
Consolidation of an aversive taste memory requires two rounds of transcriptional and epigenetic regulation in the insular cortex