The hippocampus is an area of the brain that is crucial for the formation of longterm declarative memories. This process depends on gene expression, which is regulated by intracellular signaling cascades such as the cAMP pathway. In this dissertation I describe experiments that we performed to identify the molecular mechanisms by which memory-related transcription is modified by two separate manipulations: treatment with histone deacetylase (HDAC) inhibitors, and sleep deprivation. The cAMP pathway can influence memory-related transcription by activating transcription factors such as CREB and by recruiting co-factors such as CBP that add acetyl groups to the histone proteins around which DNA is wrapped. Pharmacologically increasing histone acetylation with HDAC inhibitors enhances hippocampus-dependent memory in mice. In Chapter 2, we explored the molecular mechanisms that underlie this effect. Our results suggest that HDAC inhibitors enhance hippocampal memory processes by the activation of key genes regulated by the CREB:CBP transcriptional complex. In the second portion of this dissertation, I have examined the mechanisms by which sleep deprivation impairs hippocampus-dependent memory consolidation. In Chapter 3, we showed that a disruption of cAMP signaling contributes to the negative effect of sleep deprivation on hippocampal function. In Chapter 4, we used a broad genomic approach to identify novel genes, cellular functions, and transcription factors that are disrupted by sleep deprivation in the hippocampus.