Structural, Synaptic, and Epigenetic Dynamics of Enduring Memories

Box 2

Recent insights into epigenetic dynamics of remote memory attenuation.

In addition to memory formation and storage, a recent study also showed an epigenetic involvement into remote fear memory

attenuation [80]. In this study, permanent attenuation of remote fear memories was achieved by using a histone deacetylase-2

inhibitor (HDAC2i) in combination with reconsolidation-updating paradigms, which increased the acetylation levels of histone

H3K9/14 (AcH3). In contrast to a vehicle-treated control group that was resistant to remote memory attenuation, a significant

increase in AcH3 was noticed 1 h after remote fear memory recall in the ACC, which stayed elevated even after the extinction

training. In the HPC, no change was observed in the acetylation levels of AcH3 1 h after recall, yet a significant increase was seen in

the HDAC2i-treated group after extinction training. More specifically, this observed increase in acetylation in the HDAC2i-treated

group was detected in the promoter region of neuroplasticity-related genes such as cFos, Arc, and Igf2, which showed a concomitant

increase in expression [81]. This clearly displays that attenuating remote fear memories using an HDAC2i promotes increased

histone acetylation-mediated neuroplasticity and in turn demonstrates an epigenetic contribution to this process.