Molecular Intersection of Activity-Dependent Gene Expression and Behavior: The Transcriptomic Signature of Long-Term Memory

Consolidating nascent experiences into long-term memories involves complex neurobiological mechanisms. Signaling cascades triggered by neuronal activity lead to sustained changes in gene expression, ultimately stabilizing and storing memory traces at the molecular level. This chapter explores molecular underpinnings of memory formation and consolidation, emphasizing how long-term memory relies on enduring cellular changes in the brain at the level of gene expression. We distinguish between neural mechanisms underlying explicit and implicit memories, while underscoring how both depend on activity-dependent gene expression. We describe the role of a wide range of molecular regulators, including transcription factors and epigenetic modifications that modulate activity-dependent gene expression, and highlight their critical role in regulating diverse behavioral responses in animal models. We highlight recent advancements in sequencing technologies that have revolutionized our understanding of the transcriptomic landscape during memory formation and consolidation. This chapter concludes by highlighting the existing gaps in our knowledge and emphasizing the importance of future research in this field to explore the molecular implications of transcriptional irregularities in cognitive disorders.