Delayed orexin signaling consolidates wake and sleep: physiology and modeling

Cecilia Diniz Behn
Neurology, Harvard/Beth Israel Deaconess Medical Center

(March 13, 2008 10:30 AM - 11:30 AM)

Delayed orexin signaling consolidates wake and sleep: physiology and modeling

Abstract

Orexin-producing neurons are clearly essential for the regulation of wakefulness and sleep as loss of these cells produces narcolepsy. However, little is understood about how these neurons dynamically interact with other wake- and sleep-regulatory nuclei to control behavioral states. Using survival analysis of wake bouts in wild type and orexin knockout mice, we characterized the fragmentation of wakefulness observed in orexin knockout mice and identified a surprisingly delayed onset (> 1 min) of functional orexin effects. We incorporated these findings into a mathematical model of the mouse sleep/wake network, and the resulting simulated behavior accurately reflects the fragmented sleep/wake behavior of narcolepsy. Analysis of the model geometry provides insight into the mechanism associated with behavioral state instability in the simulated data and leads to several predictions.