The HDAC inhibitor CI-994 acts as a molecular memory aid by facilitating synaptic and intracellular communication after learning

Abstract

Significance Memory formation relies on a plethora of functions, including epigenetic modifications. Over recent years, multiple studies have indicated the potential of HDAC inhibitors (HDACis) as cognitive enhancers, but their mode of action is not fully understood. Here, we tested whether HDACi treatment improves memory formation via “cognitive epigenetic priming,” stipulating that HDACis—without inherent target specificity—specifically enhance naturally occurring plasticity processes. We found that combining HDACis with fear learning, but not either treatment alone, enhances synaptic plasticity as well as memory-promoting transcriptional signaling in the hippocampus, a brain area recruited by fear learning, but not in unrelated areas. These results lend experimental support to the theory of cognitive epigenetic priming.