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REM sleep dynamics in a mouse model of narcolepsy

Lin, Shin-Hsien
; 
Stowe, Shelby R.
; 
Coffey, Alissa
; 
Scammell, Thomas E.
; 
Diniz Behn, Cecilia
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2026-04
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2026 Spring Undergraduate Research Symposium
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https://hdl.handle.net/11124/182008
 https://doi.org/10.25676/11124/182008
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Abstract
Type 1 narcolepsy (NT1) is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, and dysregulation of rapid-eye-movement (REM) sleep caused by the loss of orexin neurons in the hypothalamus. In this study, we used orexin-tTA; TetO-DTA mice, a rodent model of narcolepsy in which progressive orexin cell loss is initiated by removing doxycycline (DOX-) from the diet to induce a phenotype similar to NT1. These mice were assessed at baseline (DOX+), three, and thirteen weeks after DOX-. Electroencephalography (EEG) and electromyography (EMG) data were collected over 24 hours, and sleep states were scored every 10 seconds. While previous analyses of these data found that total REM sleep duration was similar across all groups, other aspects of REM sleep were not considered. Markers of REM homeostasis, such as the positive correlation between the duration of a REM bout and the succeeding NREM bout, were preserved with the loss of the orexin neurons. However, while the total REM bout count was conserved in the DOX- group, the DOX- mice had significantly fewer REM bouts within continuous REM-NREM-REM cycles. Furthermore, although the durations of NREM intervals between REM bouts in the control group followed a bimodal Gaussian Mixture Model (GMM), data from the DOX- population could not be fitted using the same model. These findings suggest that although some features of REM sleep are unaffected by orexin cell loss, there is a key difference in sleep architecture that becomes more apparent with disease progression.
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