Sleep serves a number of functions, including memory storage and synaptic plasticity. One of the most prevalent complaints in the elderly is the dysregulation of sleep/wake patterns and daytime sleepiness. The goal of our research is to define how sleep is altered with age and to identify the molecular mechanisms underlying age-related deterioration of sleep/wake. Because aging is accompanied by alterations in both sleep and memory, defining the role of sleep may help us understand the behavioral, cellular and molecular changes that occur during aging and enable us to identify therapeutic approaches that might reverse these alterations. Aging is associated with increased sleep fragmentation, and the inability to sustain sleep/wake states. What are the underlying mechanisms of these disruptions? What are the consequences of these changes? How do these changes affect the function of sleep? The experiments in this project focus on the molecular and cellular mechanisms responsible for the dysregulation of sleep/wake in aged mice. Our work reveals that the CREB signaling pathway is required to promote and sustain wakefulness. Our proposed research begins by mapping where CREB is required to sustain wakefulness in the brain across the lifespan of mice (Specific Aim 1). We then examine where CREB signaling is reduced in aged animals and how these changes affect gene expression (Specific Aim 2).
In Specific Aim 3, we attempt to rescue age- related fragmentation of sleep/wake by increasing CREB signaling in the brain. Together, the proposed experiments will define how sleep/wake patterns are altered by aging and will identify the molecular and cellular mechanisms underlying these age-related alterations in sleep/wake.
Aging is accompanied by the fragmentation of sleep/wake states and daytime sleepiness. We seek to understand the molecular basis of these age-related changes in sleep to enable us to develop therapeutic approaches to treat the sleep alterations that occur with aging.
|Anafi, Ron C; Lee, Yool; Sato, Trey K et al. (2014) Machine learning helps identify CHRONO as a circadian clock component. PLoS Biol 12:e1001840|
|Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer et al. (2014) Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory. Neurobiol Learn Mem 109:122-30|
|Nall, Aleksandra H; Sehgal, Amita (2013) Small-molecule screen in adult Drosophila identifies VMAT as a regulator of sleep. J Neurosci 33:8534-40|
|Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R et al. (2013) Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues. BMC Genomics 14:362|
|Vecsey, Christopher G; Wimmer, Mathieu E J; Havekes, Robbert et al. (2013) Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in mice. Sleep 36:601-7|
|Prince, Toni-Moi; Abel, Ted (2013) The impact of sleep loss on hippocampal function. Learn Mem 20:558-69|
|Naidoo, Nirinjini; Ferber, Megan; Galante, Raymond J et al. (2012) Role of Homer proteins in the maintenance of sleep-wake states. PLoS One 7:e35174|
|Zimmerman, John E; Chan, May T; Jackson, Nicholas et al. (2012) Genetic background has a major impact on differences in sleep resulting from environmental influences in Drosophila. Sleep 35:545-57|
|McShane, Blakeley B; Galante, Raymond J; Biber, Michael et al. (2012) Assessing REM sleep in mice using video data. Sleep 35:433-42|
|Sehgal, Amita; Mignot, Emmanuel (2011) Genetics of sleep and sleep disorders. Cell 146:194-207|
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