Frontiers of Neurology and Neuroscience最新文献

{"title":"Hypocretin/Orexin Receptor Pharmacology and Sleep Phases.","authors":"Yu Sun,&nbsp;Ryan K Tisdale,&nbsp;Thomas S Kilduff","doi":"10.1159/000514963","DOIUrl":"https://doi.org/10.1159/000514963","url":null,"abstract":"<p><p>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. The broad projections of the hypocretin/orexin-producing neurons, along with differential expression of the two receptors in the projection fields of these neurons, suggest distinct roles for these receptors. While HCRTR1/OX1R is associated with regulation of motivation, reward, and autonomic functions, HCRTR2/OX2R is strongly linked to sleep-wake control. The association of hypocretin/orexin with these physiological processes has led to intense interest in the therapeutic potential of compounds targeting these receptors. Agonists and antagonists for the hypocretin/orexin receptors have shown potential for the treatment of disorders of excessive daytime somnolence and nocturnal hyperarousal, respectively, with the first antagonists approved by the US Food and Drug Administration (FDA) in 2014 and 2019 for the treatment of insomnia. These and related compounds have also been useful tools to advance hypocretin/orexin neurobiology.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"22-37"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514963","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39046951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twenty-Three Years of Hypocretins: The \"Rosetta Stone\" of Sleep/Arousal Circuits.","authors":"Luis de Lecea","doi":"10.1159/000514961","DOIUrl":"https://doi.org/10.1159/000514961","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514961","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prelims.","authors":"","doi":"10.1159/000514976","DOIUrl":"https://doi.org/10.1159/000514976","url":null,"abstract":"","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"I-VIII"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39046959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Signaling Mechanisms of Hypocretin/Orexin.","authors":"Jyrki P Kukkonen,&nbsp;Pauli M Turunen","doi":"10.1159/000514962","DOIUrl":"https://doi.org/10.1159/000514962","url":null,"abstract":"<p><p>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. In the central nervous system neurons, the main acute downstream responses of OXR activation are the inhibition of K+ channels and the activation of the Na+/Ca2+ exchanger and non-selective cation channels of unknown identity. The exact nature of the intracellular signal chain between the OXRs and these downstream targets is yet to be elucidated, but the Gq-phospholipase C (PLC) protein kinase C pathway - which is a significant signaling pathway for OXRs in recombinant cells - may be one of the players in neurons. The Gq-PLC pathway may also, under certain circumstances, take the route to diacylglycerol lipase, which leads to the production of the potent endocannabinoid (eCB), 2-arachidonoyl glycerol, and thereby connects orexins with eCB signaling. In addition, OXRs have been studied in the context of neurodegeneration and cancer cell death. Overall, OXR signaling is complex, and it can change depending on the cell type and environment.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"91-102"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514962","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39046950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subsecond Ensemble Dynamics of Orexin Neurons Link Sensation and Action.","authors":"Denis Burdakov","doi":"10.1159/000514957","DOIUrl":"https://doi.org/10.1159/000514957","url":null,"abstract":"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. Neural ensemble calcium imaging experiments reveal that the same orexin cells whose activity underlies movement initiation display subsecond-latency responses to diverse sensory stimuli. These findings establish orexin neurons as rapid and strong sensorimotor controllers that are in many ways operationally similar to classic subcortical movement controllers, such as midbrain dopamine neurons. While a scientific definition of \"arousal\" is still lacking, the subsecond-scale sensorimotor control by orexin neurons could be viewed as reminiscent of a motor rather than an arousal system.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"52-60"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514957","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep Problems in Narcolepsy and the Role of Hypocretin/Orexin Deficiency.","authors":"Emmanuel Mignot,&nbsp;Jamie Zeitzer,&nbsp;Fabio Pizza,&nbsp;Giuseppe Plazzi","doi":"10.1159/000514959","DOIUrl":"https://doi.org/10.1159/000514959","url":null,"abstract":"<p><p>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. Narcolepsy is also associated with an inability to consolidate sleep, a more complex phenotype that may result from secondary changes or be central to the role of hypocretin in coordinating the activity of other sleep- and wake-promoting systems. Novel technologies, such as the use of deep learning analysis of electroencephalographic signals, is revealing a complex pattern of sleep abnormalities in human narcolepsy that can be used diagnostically. The availability of novel devices measuring sleep 24 h per day also holds promise to provide new insights into how brain electrical activity and muscle tone are regulated by hypocretin.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"103-116"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514959","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep and Metabolism: Implication of Lateral Hypothalamic Neurons.","authors":"Lukas T Oesch,&nbsp;Antoine R Adamantidis","doi":"10.1159/000514966","DOIUrl":"https://doi.org/10.1159/000514966","url":null,"abstract":"<p><p>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. It further confirms the dual sleep-metabolic functions of LH cells, and sheds light on a possible mechanism underlying brain plasticity during sleep and metabolic disorders.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"75-90"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514966","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39046954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep, Orexin and Cognition.","authors":"Balmeet Toor,&nbsp;Laura B Ray,&nbsp;Alyssa Pozzobon,&nbsp;Stuart M Fogel","doi":"10.1159/000514960","DOIUrl":"https://doi.org/10.1159/000514960","url":null,"abstract":"<p><p>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. Thus, novel orexin therapies have the potential to either improve memory, cognition, and daytime performance directly or indirectly, through promotion of good sleep. The full scope of the therapeutic potential of orexin therapies remains to be elucidated.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"45 ","pages":"38-51"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000514960","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A History of Neuropsychology","authors":"J. Bogousslavsky, F. Boller, 岩田 誠","doi":"10.1159/isbn.978-3-318-06463-6","DOIUrl":"https://doi.org/10.1159/isbn.978-3-318-06463-6","url":null,"abstract":"Neuropsychology has become a very important aspect for neurologists in clinical practice as well as in research. Being a specialized field in psychology, its long history is based on different historical developments in brain science and clinical neurology. In this volume, we want to show how present concepts of neuropsychology originated and were established by outlining the most important developments since the end of the 19th century. The articles of this book that cover topics such as aphasia, amnesia and dementia show a great multicultural influence due to an editorship and authorship that spans all developmental initiatives in Europe, Asia, and America. This book gives a better understanding of the development of higher brain function studies and is an interesting read for neurologists, psychiatrists, psychologists, neurosurgeons, historians, and anyone else interested in the history of neuropsychology.","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82555790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early History of Amnesia.","authors":"Karen G Langer","doi":"10.1159/000494953","DOIUrl":"https://doi.org/10.1159/000494953","url":null,"abstract":"<p><p>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. Etiologic factors included neurological disorders of stroke, hemorrhage, and head injury, metabolic dysregulation, alcohol and substance abuse, toxicity, anoxia, and other acute or chronic (sometimes progressive) brain disorders. Clinical descriptions of amnesia appeared internationally in medical dictionaries and scientific encyclopedias in the early 19th century. The possibility that amnesia could be either idiopathic, or symptomatic of another illness, was proposed based on the wide range of recognized etiologies and associations. Debate ensued regarding the status of amnesia as an illness or a symptom, but regardless, amnesia was soon recognized as an independent disorder of memory, distinguishable from disorders of global intellect, or of consciousness, or of language. Distinctions of amnesia considered its temporal gradient, duration and natural course, nature of onset, severity or depth of memory loss, course, and prognosis. Concepts of retrograde (forgetting knowledge preceding onset) and anterograde (difficulty learning, recalling new information) further specified the nature of amnestic memory difficulty. Alcoholic amnesia in Korsakoff's syndrome generated much attention. Amnesia as a clinical feature was critical to the development of notions of dissociation of conscious from subconscious recall in hysteria, and differentiation of neurogenically-based from psychogenically-based amnesia became central to understanding post-traumatic states. Amnesia studied as a disorder of memory remains an avenue to enrich clinical understanding of a condition that continues to be powerfully challenging to this day.</p>","PeriodicalId":35285,"journal":{"name":"Frontiers of Neurology and Neuroscience","volume":" ","pages":"64-74"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000494953","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37347176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}