The study investigates the regulation of histone acetylation during the formation of long-term memory in the hippocampus. Specifically, it examines the changes in histone H3 acetylation in area CA1 of the hippocampus following contextual fear conditioning, a paradigm used to induce long-term memory. The research shows that contextual fear conditioning increases acetylation of histone H3, which is dependent on the activation of N-methyl-D-aspartic acid (NMDA) receptors and extracellular signal-regulated kinase (ERK). This increase in histone H3 acetylation is blocked by a behavioral latent inhibition paradigm. In vitro experiments demonstrate that activation of NMDA receptors and ERK signaling pathways in hippocampal slices also increase histone H3 acetylation. Additionally, elevation of histone acetylation using histone deacetylase inhibitors (such as trichostatin A and sodium butyrate) enhances the induction of long-term potentiation (LTP) at Schaffer-collateral synapses in area CA1, suggesting a role for histone acetylation in memory formation. Furthermore, injection of sodium butyrate into animals prior to contextual fear conditioning enhances the formation of long-term memory. These findings indicate that histone-associated heterochromatin undergoes structural changes during the formation of long-term memory, and that mimicking these changes can enhance the cellular process of long-term potentiation, contributing to memory formation.The study investigates the regulation of histone acetylation during the formation of long-term memory in the hippocampus. Specifically, it examines the changes in histone H3 acetylation in area CA1 of the hippocampus following contextual fear conditioning, a paradigm used to induce long-term memory. The research shows that contextual fear conditioning increases acetylation of histone H3, which is dependent on the activation of N-methyl-D-aspartic acid (NMDA) receptors and extracellular signal-regulated kinase (ERK). This increase in histone H3 acetylation is blocked by a behavioral latent inhibition paradigm. In vitro experiments demonstrate that activation of NMDA receptors and ERK signaling pathways in hippocampal slices also increase histone H3 acetylation. Additionally, elevation of histone acetylation using histone deacetylase inhibitors (such as trichostatin A and sodium butyrate) enhances the induction of long-term potentiation (LTP) at Schaffer-collateral synapses in area CA1, suggesting a role for histone acetylation in memory formation. Furthermore, injection of sodium butyrate into animals prior to contextual fear conditioning enhances the formation of long-term memory. These findings indicate that histone-associated heterochromatin undergoes structural changes during the formation of long-term memory, and that mimicking these changes can enhance the cellular process of long-term potentiation, contributing to memory formation.