THOMAS SCAMMELL

..These robust pathways suggest candidate mechanisms by which sleep may be influenced by brain systems regulating arousal, autonomic, limbic, and circadian functions...

..These observations suggest that PGD2 may induce sleep via leptomeningeal PGD2 receptors with subsequent activation of the VLPO...

..An up-to-date understanding of these systems should allow clinicians and researchers to better understand the effects of drugs, lesions, and neurologic disease on sleep and wakefulness...

..This working definition provides helpful insights into murine cataplexy and should allow objective and accurate comparisons of cataplexy in future studies using mouse models of narcolepsy...

..As the orexin system mainly promotes arousal, these new compounds will likely improve insomnia without incurring many of the side effects encountered with current medications...

..Instead, the fragmented behavior of orexin KO mice may be best described as behavioral state instability, with apparently low thresholds to transition between states...

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..We developed an EEG spectral analysis technique to determine whether the state instability in a mouse model of narcolepsy reflects abnormal sleep or wake states, faster movements between states, or abnormal transitions between states...

..These results demonstrate that histaminergic neurons throughout the TMN are wake-active, and this activity is largely independent of the time of day...

..People with narcolepsy and mice lacking orexin/hypocretin have disrupted sleep/wake behavior and reduced physical activity. Our objective was to identify physiologic mechanisms through which orexin deficiency reduces locomotor activity...

..Because circadian and other factors alter the fine architecture of sleep-wake behavior, this model provides a novel framework to explore dynamical principles that may underlie normal and pathologic sleep-wake physiology...

..These results raise doubts about whether enteric neurons produce hypocretin...

..We also review how homeostatic, circadian, and allostatic drives help regulate sleep state switching and discuss how breakdown of the switching mechanism may contribute to sleep disorders such as narcolepsy...

..In addition, because heat loss is an essential aspect of sleep, the blunted fall in Tb of orexin KO mice may provide an explanation for the fragmented sleep of narcolepsy...

..These observations suggest that the orexin neurons may integrate a variety of interoceptive and homeostatic signals to increase behavioral arousal in response to hunger, stress, circadian signals, and autonomic challenges...

..Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep...

..These findings explain how various drugs affect sleep and wakefulness, and provide the basis for a wide range of environmental influences to shape wake-sleep cycles into the optimal pattern for survival...

..These discoveries have considerably improved our understanding of the neurobiology of sleep and should foster the development of rational treatments for a variety of sleep disorders...

..The gait difficulties resolved with venlafaxine. This case demonstrates that status cataplecticus can be misdiagnosed as a psychogenic gait disorder...

..Electrophysiological studies have now identified positive and negative feedback signals that allow the orexin neurons to help maintain wakefulness...

..Through these pathways, the DMH may influence a wide range of behavioral circadian rhythms...

..These results implicate EGF receptor signalling in the daily control of locomotor activity, and they identify a neural circuit in the hypothalamus that likely mediates the regulation of behaviour both by the SCN and the retina...

..Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk- and reward-seeking behaviors, including substance abuse...

..This transduction knock-out technique holds enormous potential for dissecting the functions of different CNS pathways...

..Our findings suggest common dynamical features of brief awakenings and sleep durations across species and may provide insights into the dynamics of the neural circuits controlling sleep...

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..These studies will provide important insights into the pre-optic and basal forebrain sites and mechanisms through which AD induces sleep. ..

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