Sleep And Activity Problems In Mouse Models Of Neurodevelopmental Disorders

Adequate sleep is important for long-term health and day-to-day function. Compared to the general population, patients diagnosed with neurodevelopmental disorders have substantially higher prevalence of sleep, activity, and circadian problems, dramatically affecting their quality of life, and potentially exacerbating other adverse symptomologies. Despite this, the neurobiological underpinnings of sleep problems in neurodevelopmental disorders remain unknown, and accurate rodent models capable of recapitulating human sleep and activity problems are lacking. In this dissertation, I investigate sleep, activity, and circadian rhythms in genetic mouse models of human neurodevelopmental disorders, with a focus on autism spectrum disorder (ASD). In Chapter 1, I review the importance of—and mechanisms contributing to—sleep/wake regulation, sleep problems in neurodevelopmental disorders, and the utility of rodent genetic models to address these problems. In Chapter 2, I investigate hyperactivity and male-specific sleep deficits found in the 16p11.2 del/+ chromosomal copy number variation mouse model of neurodevelopmental disorders (Angelakos et al., 2016). In Chapter 3, I highlight REM sleep reductions and altered electroencephalography (EEG) spectra in the SYGNAP1+/- mouse model of intellectual disability and ASD. In Chapter 4, I discuss home-cage hypoactivity observed in four different mouse models of ASD