Semester

Fall

Date of Graduation

2025

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Psychology

Committee Chair

Michelle Bridi

Committee Co-Chair

James Walton

Committee Member

Charles Anderson

Committee Member

Mariya Cherkasova

Abstract

Sleep plays a crucial role in memory consolidation, neuronal plasticity, and cognitive function. Individuals with autism spectrum disorder (ASD) often experience sleep disturbances, which are positively correlated with symptom severity. However, on the surface, sleep architecture is remarkably normal under baseline conditions in many rodent models of ASD. The goals if this dissertation were to investigate whether regulation of sleep, biochemical signaling during sleep, and downstream consequences of sleep on behavior are altered in two mouse models of ASD. In Aim 1, we tested the hypothesis that sleep phenotypes emerge in ASD models under conditions of high sleep pressure. We used electroencephalogram (EEG) and electromyogram (EMG) recordings to examine sleep architecture and spectral properties following sleep deprivation in the BTBR and fmr1-KO mouse models of ASD. We observed an insomnia-like phenotype where BTBR mice had a longer latency to enter their first bout of sleep following sleep deprivation. Further, BTBR mice spent a significantly shorter time in REM but not wake or NREM following being sleep deprived than B6 mice. In Aim 2, we investigated the relationship between endocannabinoid (eCB) signaling and sleep. eCB signaling varies across sleep/wake states, is altered in ASD, and modulates inhibitory signaling in the brain, suggesting it may influence sleep's effects on cognition. We implanted fiberoptic cannulas along with a virus that encodes a fluorescent eCB-specific biosensor into visual cortex, starting with B6 mice to establish typical eCB signaling patterns. We utilized fiber photometry to visualize eCB signaling, but due to technical issues only observed weak construct expression and no biologically relevant signal during in vivo recordings. Lastly, in Aim 3 we assessed whether visual discrimination depends on sleep/wake history in B6 mice, with the goal of determining whether this relationship is altered in ASD-related mouse lines. Sleep regulates inhibition in wildtype (WT) mice, but this relationship is atypical in ASD models, and altered inhibition modifies sensory processing. Therefore, we assessed whether visual discrimination differs following sleep-enriched vs. wake-enriched periods using a 2-choice visual discrimination task, starting with B6 mice. However, we found that this task was not suitable to answer our experimental question due to the long task acquisition time and high proportion of mice that fail to learn. We therefore pivoted to piloting a fear-conditioning-based visual discrimination task. Taken together, the results of our study demonstrated how sleep/wake physiology is altered in ASD mice and reveal viable strategies for determining its downstream consequences.

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