Frontiers of Neurology and Neuroscience

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Advances in translational research provide key opportunities to explore the physiological and pathological effects of sleep in different neurodegenerative diseases. Recent findings suggest that sleep-wakefulness dysfunctions may predispose to neurodegenerative disorders such as Alzheimer's disease (AD), and vice versa. New theories on the link between sleep and β-amyloid and tau secretion, accumulation and clearance, and its interaction with hypocretins/orexins (key neuropeptides regulating wakefulness) suggest mechanistic ways to better understand the impact of sleep alterations in the pathogenesis of AD...

During the last decade, optogenetic-based circuit mapping has become one of the most common approaches to systems neuroscience, and amassing studies have expanded our understanding of brain structures causally involved in the regulation of sleep-wake cycles. Recent imaging technologies enable the functional mapping of cellular activity, from population down to single-cell resolution, across a broad repertoire of behaviors and physiological processes, including sleep-wake states. This chapter summarizes experimental evidence implicating hypocretins/orexins, melanin-concentrating hormone, and inhibitory neurons from the lateral hypothalamus (LH) in forming an intricate network involved in regulating sleep and metabolism, including feeding behaviors...

Significant sleep impairments often accompany substance use disorders (SUDs). Sleep disturbances in SUD patients are associated with poor clinical outcomes and treatment adherence, emphasizing the importance of normalizing sleep when treating SUDs. Orexins (hypocretins) are neuropeptides exclusively produced by neurons in the posterior hypothalamus that regulate various behavioral and physiological processes, including sleep-wakefulness and motivated drug taking. Given its dual role in sleep and addiction, the orexin system represents a promising therapeutic target for treating SUDs and their comorbid sleep deficits...

The multifunctional, hypothalamic hypocretin/orexin (HCRT)-producing neurons regulate an array of physiological and behavioral states including arousal, sleep, feeding, emotions, stress, and reward. How a presumably uniform HCRT neuron population regulates such a diverse set of functions is not clear. The role of the HCRT neuropeptides may vary depending on the timing and localization of secretion and neuronal activity. Moreover, HCRT neuropeptides may not mediate all functions ascribed to HCRT neurons. Some could be orchestrated by additional neurotransmitters and neuropeptides that are expressed in HCRT neurons...

The hypocretins/orexins are two excitatory neuropeptides, alternately called HCRT1 or orexin-A and HCRT2 or orexin-B, that are the endogenous ligands for two G-protein-coupled receptors, HCRTR1/OX1R and HCRTR2/OX2R. Shortly after the discovery of this system, degeneration of hypocretin/orexin-producing neurons was implicated in the etiology of the sleep disorder narcolepsy. The involvement of this system in a disorder characterized by the loss of control over arousal state boundaries also suggested its role as a critical component of endogenous sleep-wake regulatory circuitry...

Orexin receptors (OXRs) are promiscuous G-protein-coupled receptors that signal via several G-proteins and, putatively, via other proteins. On which basis the signal pathways are selected and orchestrated is largely unknown. We also have an insufficient understanding of the kind of signaling that is important for specific types of cellular responses. OXRs are able to form complexes with several other G-protein-coupled receptors in vitro, and one possibility is that the complexing partners regulate the use of certain signal transducers...

The discovery of the hypocretins/orexins (HCRTs) has revolutionized sleep science in the last two decades. A combination of anatomical tracing methods, optogenetics, and pharmacology is delineating a blueprint of functional inputs and outputs of the HCRT system. Here, we discuss several models of HCRT action that involve the integration between physiological variables, circadian output, and sleep homeostasis. Generation of activity maps during the sleep-wake cycle at the cellular level will allow investigators to decipher computational frameworks modeling operations of HCRT networks...

Orexins regulate a wide variety of biological functions, most notably the sleep-wake cycle, reward and stress processing, alertness, vigilance, and cognitive functioning. Alterations of central and peripheral orexin levels are linked to conditions such as narcolepsy, anorexia nervosa, age-related cognitive decline, and neurodegenerative disease. Preliminary studies suggest that orexin mimetics can safely promote the wake signal via orexin agonism during the day and that orexin receptor antagonists can promote the sleep signal during the night...

Since its description in the 19th century, narcolepsy type 1 (NT1) has been considered as a model sleep disorder, and after the discovery of rapid eye movement (REM) sleep onset in the disorder, a gateway to understanding REM sleep. The discovery that NT1 is caused by hypocretin/orexin deficiency, together with neurochemical studies of this system, has helped to establish how this neuropeptide regulates the organization of sleep and wake in humans. Current analyses suggest that the main functions of the hypocretin/orexin system are (1) maintenance of wakefulness in the face of moderate sleep deprivation; (2) passive wake promotion, especially in the evening, driven by the circadian clock; (3) inhibition of REM sleep, with possible differential modulating effects on various subcomponents of the sleep-stage, explaining REM sleep dissociation events in NT1...

Hypothalamic hypocretin/orexin neurons have been initially conceptualized as slow, modulatory controllers of behavior. Furthermore, their behavioral effects have been assumed to be a secondary consequence of their impact on arousal. However, cellular-resolution calcium imaging and optogenetic studies show that orexin neurons regulate self-generated and sensory-evoked movement on rapid, subsecond timescales. Orexin cell activity rapidly and transiently peaks before and during movements. Optogenetic prevention of this activation reduces the probability of locomotion initiation, and optogenetic mimicry of orexin cell activation rapidly causes locomotion...

Sleep is one of the pillars of health. Experimental models of acute sleep loss, of chronic partial sleep deprivation, and of sleep fragmentation in healthy sleepers are helpful models of sleep deficiency produced by insufficient sleep duration, sleep timing, and sleep disorders. Sleep deficiency is associated with changes in markers associated with risk for disease. These include metabolic, inflammatory, and autonomic markers of risk. In addition, sleep disruption and sleep deficits lead to mood instability, lack of positive outlook, and impaired neurobehavioral functioning...

Orexins have received a lot of attention as potent endogenous arousal-promoting peptides, and orexin receptor antagonists have shown clinical efficacy for the treatment of insomnia. Orexin neurons are thought to act primarily on monoaminergic neurons to maintain arousal and vigilance. In this chapter, we discuss the functional interaction between monoaminergic systems, including noradrenaline, serotonin and histamine, and orexin neurons, as well as interactions between the acetylcholine system and the orexin neurons, focusing, in particular, on their function in the regulation of sleep-wakefulness states...

Hallucinations, delusions, and confabulations are common symptoms between neurology and psychiatry. The neurological diseases manifesting with such symptoms (dementia, epilepsy, Korsakoff's disease, brain tumors, Parkinson's disease, migraine, right hemisphere stroke and others) would be the key to understand their biological mechanisms, while the cognitive sciences, neuropharmacology and functional neuroimaging would be the tools of such researches. It is possible to understand the perceptive rules of the mind and the mechanisms of the human consciousness based on these symptoms...

Neuropsychological rehabilitation is one of the subspecialties of neuropsychology, along with neuropsychological assessment, cognitive process descriptions, and anatomo-functional correlation, but it is still frequently underrecognized, even from a historical point of view. In this chronological review, we propose following some of the historical descriptions of cognitive recovery, and the suggested procedures and therapies to improve this recovery from mythological periods and the antiquity to recent contemporary periods and the birth of formal neuropsychological rehabilitation in neurological and psychiatric conditions...

This chapter presents a historical overview of observations, instruments, and approaches in the area of neuropsychological assessment. In the 17th and 18th century literature dealing especially with language disorders following a brain disorder, one finds observations of physicians of striking dissociations of mental faculties that were impaired while others remained intact. Around the middle of the 19th century, neuropsychiatrists like Carl Wernicke began to develop procedures for assessing more specific components of mental functioning...

In neurology and neuropsychology, behavior refers to the way human beings act and make decisions in contact with their environment. Behavioral impairment is therefore defined as a pathology, following brain lesion, that impacts the interactions between the brain-lesioned individual and his/her surrounding social world. First descriptions of behavioral disorders, including neuroanatomical correlates, date back to the mid-19th century. However, attempts towards their systematic identification and analysis only began at the turn of the 19th to 20th century...

Memory and forgetfulness have been viewed since antiquity from perspectives of physical, emotional, and spiritual states of well-being, and conceptualized philosophically. Numerous discussions of memory loss, or case reports, existed, but a fundamental advance in conceptualization of memory loss as a pathological clinical phenomenon originated when Sauvages classified "amnesia" as a medical disorder, in 1763. Originally, amnesia was recognized as a weakening or dissolution of memory, according to a taxonomy that ascribed known causes to the disorder...

The term dementia derives from the Latin root demens, which means being out of one's mind. Although the term "dementia" has been used since the 13th century, its mention in the medical community was reported in the 18th century. Even though the Greeks postulated a cerebral origin, the concept was not restricted to senile dementia and included all sorts of psychiatric and neurological conditions leading to psychosocial consequences. In the 19th century, individuals with dementia were recognized as patients, deserving medical care from specialists called alienists, and senile dementia became a medical disease...