Resilience to acute sleep deprivation is associated with attenuation of hippocampal mediated learning impairment

Thesis (Master's)--University of Washington, 2020Sleep deprivation is a universal issue that affects individuals in differing ways. While some individuals experience a deficit in daily performance, others experience resiliency as they can maintain high levels of physical and mental functionality. Although we know that a loss of sleep causes cognitive dysfunction in areas such as learning and memory, we do not understand which neural mechanisms contribute to the attenuation of learning impairment. Recently, our laboratory produced a cognitive assay known as the Box Maze that can assess learning impairment in sleep-deprived mice. Based on data accumulated from the box maze, we hypothesized that a grading platform could separate fast and slow learners in mice that have or have not been exposed to sleep deprivation. This grade could then be further explored with biomarkers, providing insight to the attenuation of learning impairment in the hippocampi of sleep deprived, fast learning mice. This study utilized an existing database of box maze escape times across 16-18 month old, male, C57BL/6 mice that were or were not sleep deprived with all other conditions standardized. After data mining, a total of 40 mice fit the criteria for the study. The grading platform utilizes a logarithmic trend line of the box maze trials to ultimately separate fast and slow learners. The separation was based on the R2 value which represented the learning curve of each individual mouse. The results showed that sleep deprived mice had more slow learners than fast whereas control mice showed the opposite. The hippocampus of these mice then underwent immunohistochemistry to explore biomarker levels that would be insightful of the attenuated learning impairment in sleep deprived mice that were graded as fast learners. The results showed that fast learners in the sleep deprived groups, expressed similar levels of biomarkers as that of the control fast learning groups. The data provides evidence that sleep-deprived mice that performed well in a cognitive assay show less hippocampal mediated learning impairment. These findings provide the rationale for clinical investigations into neurobiological resilience with increasing age