Transcriptome and epigenome analysis of engram cells: Next-generation sequencing technologies in memory research

Transcription and epigenetic changes are integral components of the neuronal response to stimulation and have been postulated to be drivers or substrates for enduring changes in animal behavior, including learning and memory. Memories are thought to be deposited in neuronal assemblies called engrams, i.e., groups of cells that undergo persistent physical or chemical changes during learning and are selectively reactivated to retrieve the memory. Despite the research progress made in recent years, the identity of specific epigenetic changes, if any, that occur in these cells and subsequently contribute to the persistence of memory traces remains unknown. The analysis of these changes is challenging due to the difficulty of exploring molecular alterations that only occur in a relatively small percentage of cells embedded in a complex tissue. In this review, we discuss the recent advances in this field and the promise of next-generation sequencing (NGS) and epigenome editing methods for overcoming these challenges and address long-standing questions concerning the role of epigenetic mechanisms in memory encoding, maintenance and expression.