Date of Award

Spring 2025

Project Type

Thesis

Program or Major

Biological Sciences

Degree Name

Master of Science

First Advisor

Xuanmao Chen

Second Advisor

Kate Christison-Lagay

Third Advisor

Mark Lyon

Abstract

Learning and memory formation is not only essential for individuals to acquire knowledge and acquisition but also linked to a range of severe brain diseases, including Alzheimer’s Disease (AD). Establishing methods for early diagnosis of AD could give patients the opportunity to slow disease progression. Previous AD research has examined the brain activity of affected individuals when they are awake or asleep; however, brain activity under anesthesia remains understudied. Using anesthetics to theoretically block external sensory stimuli, electroencephalography (EEG) recording of the mouse brain at the lowest basal level may reflect intrinsic backbone circuitry for cognition, learning and memory formation. We recently revealed that burst synchronization of primed hippocampal neurons is key for trace fear memory formation. Wildtype (WT), Amyloid Precursor Protein 23 transgenic mice (APP23, an AD mouse model), and Ift88 flox/flox, Camk2a-Cre/ERT2 knockouts (forebrain-specific inducible cilia KOs) were used in our study. Mice were exposed to 3% isoflurane until reaching a coma-like activity level where burst suppressions can be detected. We hypothesize that the EEG pattern under isoflurane in WTs, APP23, and KO will display distinct characteristics, and that the alteration of burst suppression patterns may be implicated in cognitive deficits. Our approach allows us to quantify frequency patterns of burst suppression occurrence in the control and two transgenic strain’s waveforms, while removing the influence of external environment. By isolating the burst suppressions, we calculated the characteristics of burst suppressions happening at any point during isoflurane exposure, ideally projecting a unique pattern across genotypes. Our results suggest that WTs, APP23, and KO mice exhibit different dynamics of activity: bursting activity is heightened in APP than controls while KO is not as active in burst suppression patterns. These observations suggest that analysis of bursting patterns under anesthesia may be useful in identifying an early biomarker for AD.

Available for download on Saturday, November 20, 2027

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