Elucidating the factors that facilitate or impede the extinction of remote memories is imperative for the advancement of targeted therapeutic interventions aimed at addressing maladaptive memory persistence. Despite the extensive body of research on memory processes, there is a notable paucity of studies focusing on the diminution of long-standing memory traces . Recently, our lab has identified a hippocampal remote recall engram that is a key player in remote memory attenuation (Khalaf et al., 2018, Science), yet its molecular underpinnings remain elusive. In this study, we seek to delineate the processes at work within these engram cells. Utilising the TetTag transgenic mouse model in conjunction with contextual fear conditioning, we induce a learned fear response which is then subject to attenuation through an established extinction paradigm. Neuronal assemblies activated during both the recall and post-extinction phases are subsequently labelled for analysis. Employing single-cell RNA sequencing techniques, we have identified a number of interesting candidate genes, including BDNF and the lysine demethylase KDM6B. The latter is of particular interest due to its role in cocaine-induced reconsolidation and behavioural reinstatement (Zhang et al., 2018, Neuropharm.). We currently endeavour to modulate KDM6B via precise cellular and temporally-specific gene silencing or overexpression strategies, or via systemic inhibition. In the future we aim to further understand the causal role of this molecule and related molecular pathways in remote memory extinction alongside associated epigenetic alterations. This will aid in the understanding of fundamental processes underlying extinction and reconsolidation, as well as provide insight into potential pharmacological targets.