Thomas E Scammell

..Selective pharmacological activation of these hypothalamic regions may represent a novel approach to inducing wakefulness...

..The authors hypothesize that a loss of orexin neurons or their relevant targets may be the specific neuropathology causing this and many other cases of secondary narcolepsy...

..Orexin-containing neurons regulate wakefulness, and loss of orexin produces narcolepsy. Recent studies of mice lacking orexin neurons have shown that these cells also play essential roles in the control of feeding and energy balance...

..These ventrolateral preoptic area neurons may then coordinate the inhibition of multiple wake-promoting regions, resulting in sleep...

..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...

..These observations demonstrate that the tuberomammillary region plays an essential role in the wake-promoting effects of orexins, but orexins must stabilize sleep through other targets...

..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...

....

..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...

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

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

..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...

..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...

..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...

..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...

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

..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...

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

..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...

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

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

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

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

..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...

..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...

..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...

..By examining which prostaglandins are produced at which sites and how they interact with the nervous system, researchers have identified specific neural circuits that underlie the sickness syndrome...

..Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy. The discovery that the majority of human patients lack the hypothalamic neuropeptide hypocretin-1 has initiated a large body of new research...

..Orexin-A levels vary moderately between subjects, but are quite consistent within the same subject. Thus, for the diagnostic evaluation of narcolepsy, the time of CSF collection should have little impact...

..Most likely, this narcolepsy is a consequence of demyelination and dysfunction of hypocretin pathways, but direct injury to the hypocretin neurons may also occur...

..This review is intended to familiarize readers with the safety and efficacy of these medications, thus enabling clinicians to optimize their management of cataplexy...

..1 was deleted from cortical pyramidal neurons. These findings support the hypothesis that thalamic T-type Ca2+ channels are required to block transmission of arousal signals through the thalamus and to stabilize sleep...