This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

/pdf/control-of-sleep-and-wakefulness-51vkuya5ho.pdf

Control of Sleep and Wakefulness

The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a new leptin-sensing neuron population, multiple agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic somatostatin neuron population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinct responses in AgRP and POMC neuron subtypes. Finally, integrating our data with human genome-wide association study data implicates two previously unknown neuron populations in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred.

/pdf/a-molecular-census-of-arcuate-hypothalamus-and-median-3cckjlvtdt.pdf

A molecular census of arcuate hypothalamus and median eminence cell types

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.12445

The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors

Orexin-A and -B (also known as hypocretin-1 and -2) are neuropeptides produced in the lateral hypothalamus that promote many aspects of arousal through the OX1 and OX2 receptors. In fact, they are necessary for normal wakefulness, as loss of the orexin-producing neurons causes narcolepsy in humans and rodents. This has generated considerable interest in developing small-molecule orexin receptor antagonists as a novel therapy for the treatment of insomnia. Orexin antagonists, especially those that block OX2 or both OX1 and OX2 receptors, clearly promote sleep in animals, and clinical results are encouraging: Several compounds are in Phase III trials. 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.

/pdf/orexin-receptors-pharmacology-and-therapeutic-opportunities-1qbwnx5gyo.pdf

Orexin Receptors: Pharmacology and Therapeutic Opportunities

The initiation codon dictates that the translation initiation event exclusively begins with methionine. We report here a new technology to reprogram the initiation event, where various amino acids and those bearing Nα-acyl groups can be used as an initiator for peptide synthesis. The technology is built upon the concept of genetic code reprogramming, where methionine is depleted from the translation system and the initiation codon is reassigned to the desired amino acid. We have applied this technology to the synthesis of an antitumor cyclic peptide, G7−18NATE, closed by a physiologically stable bond, and it is also extended to the custom synthesis of its analogues with various ring sizes. Significantly, cyclization occurs spontaneously upon translation of the precursor linear peptides. To demonstrate the practicality of this methodology, we also prepared a small cyclic peptide library designated by 160 distinct mRNAs. Thus, this technology offers a new means to prepare a wide array of in vivo compatible ...

Reprogramming the translation initiation for the synthesis of physiologically stable cyclic peptides.

Aim: The effect of orexin on wakefulness has been suggested to be largely mediated by activation of histaminergic neurones in the tuberomammillary nucleus (TMN) via orexin receptor-2 (OX 2 R). However, orexin receptors in other regions of the brain might also play important roles in maintenance of wakefulness. To dissect the role of the histaminergic system as a downstream mediator of the orexin system in the regulation of sleep/wake states without compensation by the orexin receptor-1 (OX 1 R) mediated pathways, we analysed the phenotype of Histamine-1 receptor (H 1 R) and OX 1 R double-deficient (H 1 R -/- ;OX 1 R -/- ) mice. These mice lack OX 1 R-mediated pathways in addition to deficiency of H 1 R, which is thought to be the most important system in downstream of OX 2 R. Methods: We used H 1 R deficient (H 1 R -/- ) mice, H 1 R -/- ;OX 1 R -/- mice, OX 1 R and OX 2 R double-deficient (OX 1 R -/- ;OX 2 R -/- ) mice, and wild type controls. Rapid eye movement (REM) sleep, non-REM (NREM) sleep and awake states were determined by polygraphic electroencephalographic/electromyographic recording. Results: No abnormality in sleep/wake states was observed in H 1 R -/- mice, consistent with previous studies. H 1 R -/- ;OX 1 R -/- mice also showed a sleep/ wake phenotype comparable to that of wild type mice, while OX 1 R -/- ; OX 2 R -/- mice showed severe fragmentation of sleep/wake states. Conclusion: Our observations showed that regulation of the sleep/wake states is completely achieved by OX 2 R-expressing neurones without involving H I R-mediated pathways. The maintenance of basal physiological sleep/wake states is fully achieved without both H 1 and OX 1 receptors. Downstream pathways of OX 2 R other than the histaminergic system might play an important role in the maintenance of sleep/wake states.

/pdf/histamine-1-receptor-is-not-required-as-a-downstream-173canmtek.pdf

Histamine‐1 receptor is not required as a downstream effector of orexin‐2 receptor in maintenance of basal sleep/wake states

Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3 Muscarinic Receptor in Mice

Here, we report the isolation and characterization of an endogenous peptide ligand of GPR103 from rat brains. The purified peptide was found to be the 43-residue RF-amide peptide QRFP. We also describe two mouse homologues of human GPR103, termed mouse GPR103A and GPR103B. QRFP binds and activates the human GPR103, as well as mouse GPR103A and GPR103B, with nanomolar affinities in transfected cells. Systematic in situ hybridization analysis in mouse brains showed that QRFP is expressed exclusively in the periventricular and lateral hypothalamus, whereas the two receptor mRNAs are distinctly localized in various brain areas without an overlap to each other. When administered centrally in mice, QRFP induced feeding behavior, accompanied by increased general locomotor activity and metabolic rate. QRFP-induced food intake was abolished by preadministration of BIBP3226, a specific antagonist for the Y1 neuropeptide Y receptor. Hypothalamic prepro-QRFP mRNA expression was up-regulated upon fasting and in genetically obese ob/ob and db/db mice. Central QRFP administration also evoked highly sustained elevation of blood pressure and heart rate. Our findings suggest that QRFP and GPR103A/B may regulate diverse neuroendocrine and behavioral functions and implicate this neuropeptide system in metabolic syndrome.

https://www.pnas.org/content/pnas/103/19/7438.full.pdf

A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Kousaku Ohno

Author Tools

Chat about Author

Papers

Histamine‐1 receptor is not required as a downstream effector of orexin‐2 receptor in maintenance of basal sleep/wake states

Cholinergic Regulation of Orexin/Hypocretin Neurons Through M3 Muscarinic Receptor in Mice

A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice