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<p>Reconsolidation, a memory stabilization phase occurring after reactivation, depends on epigenetic mechanisms such as histone acetylation, mediated by histone acetyltransferases (HATs) like p300/CBP. The prelimbic (PL) region of the medial prefrontal cortex is involved in fear memory reconsolidation, whereas the infralimbic (IL) cortex supports memory extinction. In the PL cortex, epigenetic mechanisms mediated by HAT CBP have been implicated in fear discrimination. However, the role of HAT p300/CBP in PL and IL cortices during contextual fear memory reconsolidation is unknown. To investigate this, fear-conditioned animals received intra-PL or IL cortices administration of C646 (5 or 50&#xa0;ng/0.2uL/side), a HAT&#xa0;p300/CBP inhibitor, immediately, 1&#xa0;h, or 6&#xa0;h after memory reactivation. In the PL cortex, C646 (50&#xa0;ng) administered within 1&#xa0;h post-reactivation disrupted reconsolidation, evidenced by reduced freezing in Test A<sub>1</sub> (24&#xa0;h) and Test A<sub>2</sub> (7&#xa0;days). In the PL cortex, HAT p300/CBP inhibition 1&#xa0;h post-retrieval significantly reduced freezing behavior in Test B<sub>1.</sub> No effects were observed in the IL cortex. The effects of C646 50&#xa0;ng administered into the PL cortex depended on memory reactivation and were unrelated to alterations in anxiety-like behavior or locomotor activity. Confirming the post-retrieval involvement of histone acetylation, an enhancement of histone H3 acetylation in the PL was observed 120&#xa0;min after reactivation in vehicle-treated animals, while C646 (50&#xa0;ng) prevented this effect. These findings demonstrate the involvement of HAT p300/CBP in the PL cortex in memory reconsolidation, suggesting that, in this area, fear memory reconsolidation is regulated by epigenetic mechanisms.</p> Graphical Abstract <p></p>

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HAT p300/CBP Activity in the Prelimbic Cortex Underlies Reconsolidation of Contextual Fear Memory

  • 期刊论文

  • 发表日期：

    2025年11月15日

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  • Mariana Furtado Bergmann,
  • Jeferson Machado Batista Sohn,
  • Ana Maria Raymundi,
  • Manoela de Aguiar Ferreira,
  • Cristina Aparecida Jark Stern

摘要

Reconsolidation, a memory stabilization phase occurring after reactivation, depends on epigenetic mechanisms such as histone acetylation, mediated by histone acetyltransferases (HATs) like p300/CBP. The prelimbic (PL) region of the medial prefrontal cortex is involved in fear memory reconsolidation, whereas the infralimbic (IL) cortex supports memory extinction. In the PL cortex, epigenetic mechanisms mediated by HAT CBP have been implicated in fear discrimination. However, the role of HAT p300/CBP in PL and IL cortices during contextual fear memory reconsolidation is unknown. To investigate this, fear-conditioned animals received intra-PL or IL cortices administration of C646 (5 or 50 ng/0.2uL/side), a HAT p300/CBP inhibitor, immediately, 1 h, or 6 h after memory reactivation. In the PL cortex, C646 (50 ng) administered within 1 h post-reactivation disrupted reconsolidation, evidenced by reduced freezing in Test A1 (24 h) and Test A2 (7 days). In the PL cortex, HAT p300/CBP inhibition 1 h post-retrieval significantly reduced freezing behavior in Test B1. No effects were observed in the IL cortex. The effects of C646 50 ng administered into the PL cortex depended on memory reactivation and were unrelated to alterations in anxiety-like behavior or locomotor activity. Confirming the post-retrieval involvement of histone acetylation, an enhancement of histone H3 acetylation in the PL was observed 120 min after reactivation in vehicle-treated animals, while C646 (50 ng) prevented this effect. These findings demonstrate the involvement of HAT p300/CBP in the PL cortex in memory reconsolidation, suggesting that, in this area, fear memory reconsolidation is regulated by epigenetic mechanisms.

Graphical Abstract