Consequences of Brief Periods of Sleep Loss on Hippocampus-Dependent Memory and Synaptic Plasticity

Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are dysregulated by sleep deprivation to impair memory consolidation and plasticity. In this dissertation, I describe experiments that we performed to identify the time window where memory consolidation is sensitive to sleep loss as well as to characterize two potential molecular players targeted by sleep deprivation. Because consolidation appears to have a particular window where it is sensitive to sleep loss, we explore the parameters of this time window in Chapter 2. Our results suggest that a specific 3-hour period of sleep loss during consolidation disrupts both memory and plasticity. In the second portion of this dissertation, I examine the mechanisms by which sleep deprivation impairs hippocampus-dependent memory consolidation. In Chapter 3, we show that loss of the phosphodiesterase (PDE) 4A, an enzyme responsible for decreasing cAMP signaling, rescues spatial memory disrupted by sleep loss. These results further implicate cAMP signaling with the negative effects of sleep deprivation on memory. Obtaining adequate sleep is challenging in a society that values work around the clock. Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is critical. However, a limited number of therapeutics exists that are able to enhance cognition in the face of insufficient sleep. The identification of the temporal characteristics of sleep loss and the molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs