We are also exploring processes that can modulate long-term memory. For example, the biological function of sleep has remained elusive, but studies suggest that one function of sleep may be to mediate memory storage. First, sleep appears to facilitate the formation of hippocampus-dependent memories, and sleep is increased following training. Second, sleep appears to be regulated by many of the same molecular processes that contribute to memory storage, including the transcription factor cAMP response element-binding protein (CREB) and the PKA signaling pathway. By using conditional genetic approaches and gene expression studies, we are striving to elucidate the machinery underlying sleep/wake regulation and define the role of sleep in the consolidation of long-term memory. Our studies have revealed that sleep deprivation impairs memory consolidation and synaptic plasticity by impairing signaling through the cAMP pathway and altering protein synthesis.