The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradic...

Advances in translational research provide key opportunities to explore the physiological and pathological effects of sleep different neurodegenerative diseases. Recent findings suggest that sleep-wakefulness dysfunctions may predispose disorders such as Alzheimer’s disease (AD), vice versa. New theories on link between β-amyloid tau secretion, accumulation clearance, its interaction with hypoc...

The basic elements of animal behavior that are critical to survival include energy, arousal, and motivation: Energy intake and expenditure are fundamental to all organisms for the performance of any type of function; according to the Yerkes-Dodson law, an optimal level of arousal is required for animals to perform normal functions; and motivation is critical to goal-oriented behaviors in higher...

In the past, studies on stress responses and sleep/wake regulation were performed separately. The discovery of orexin (hypocretin) in 1998, however, dramatically changed the course of research and new findings regarding its role in these complex processes provided a better insight into their interactions and intricacies. Orexin-containing neuronal activity has been found to be minimal during sl...

BACKGROUND Neurophysiological and behavioral processes regulated by hypocretin (orexin) are severely affected in depression. However, alterations in hypocretin have so far not been studied in the human brain. We explored the hypocretin system changes in the hypothalamus and cortex in depression from male and female subjects. METHODS We quantified the differences between depression patients an...

Sleep disturbances in Alzheimer's disease (AD) patients are associated with the severity of dementia and are often the primary reason for institutionalization. These sleep problems partly resemble core symptoms of narcolepsy, a sleep disorder caused by a general loss of the neurotransmitter hypocretin. AD is a neurodegenerative disorder targeting different brain areas and types of neurons. In t...

Orexin/hypocretin neurons have a crucial role in the regulation of sleep and wakefulness. To help determine how these neurons promote wakefulness, we generated transgenic mice in which orexin neurons expressed halorhodopsin (orexin/Halo mice), an orange light-activated neuronal silencer. Slice patch-clamp recordings of orexin neurons that expressed halorhodopsin demonstrated that orange light p...