المؤلفون: Gary B. Kaplan, Gabrielle A. Lakis, Hryhoriy Zhoba

المصدر: Brain Research Bulletin, Vol 186, Iss , Pp 106-122 (2022)

مصطلحات موضوعية: Orexin, Orexin receptors, Neuropeptide, PTSD, Arousal, Sleep, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Post-traumatic stress disorder (PTSD) is a trauma-related condition that produces distressing fear memory intrusions, avoidance behaviors, hyperarousal/startle, stress responses and insomnia. This review focuses on the importance of the orexin neural system as a novel mechanism related to the pathophysiology of PTSD. Orexinergic neurons originate in the lateral hypothalamus and project widely to key neurotransmitter systems, autonomic neurons, the hypothalamic-pituitary-adrenal (HPA) axis, and fear-related neural circuits. After trauma or stress, the basolateral amygdala (BLA) transmits sensory information to the central nucleus of the amygdala (CeA) and in turn to the hypothalamus and other subcortical and brainstem regions to promote fear and threat behaviors. Orexin receptors have a prominent role in this circuit as fear conditioned orexin receptor knockout mice show decreased fear expression while dual orexin receptor antagonists (DORAs) inhibit fear acquisition and expression. Orexin activation of an infralimbic-amygdala circuit impedes fear extinction while DORA treatments enhance it. Increased orexin signaling to the amygdalo-cortical-hippocampal circuit promotes avoidance behaviors. Orexin has an important role in activating sympathetic nervous system (SNS) activity and HPA axis stress responses. Blockade of orexin receptors reduces fear-conditioned startle responses. In PTSD models, individuals demonstrate sleep disturbances such as increased sleep latency and more transitions to wakefulness. Increased orexin activity impairs sleep by promoting wakefulness and reducing total sleep time while DORA treatments enhance sleep onset and maintenance. The orexinergic neural system provides important mechanisms for understanding multiple PTSD behaviors and provides new medication targets to treat this often persistent and debilitating illness.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S0361923022001216Test; https://doaj.org/toc/1873-2747Test

الوصول الحر: https://doaj.org/article/2aeb9192955d4781abbc7fa66cec5e5fTest

المؤلفون: Mayda Rivas, Annabel Ferreira, Pablo Torterolo, Luciana Benedetto

المصدر: Frontiers in Behavioral Neuroscience, Vol 17 (2023)

مصطلحات موضوعية: hypocretin (orexin), neuropeptide, hypothalamus, medial preoptic area (mPOA), wakefulness, sleep, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1184885/fullTest; https://doaj.org/toc/1662-5153Test

الوصول الحر: https://doaj.org/article/933f01be5be54827a81033488c06e1efTest

المؤلفون: Suresh, Vinay, Bardhan, Mainak, Ghosh, Shankhaneel, Chandani, Yash, Satapathy, Prakasini, Roy, Priyanka, Shamim, Muhammad Aaqib, Gandhi, Aravind P, Sandeep, Mokanpally, Rustagi, Sarvesh, Sah, Ranjit, Padhi, Bijaya K

المصدر: Clin Neurol Neurosurg ; ISSN:1872-6968 ; Volume:242

مصطلحات موضوعية: Neuropeptide, Orexin-A, Parkinson’s disease, Sleep dysregulation

الوصف: Parkinson's disease (PD) is a progressive neurological condition that affects movement and coordination. Orexin-A (OXA) is an excitatory neuropeptide that is found throughout the central nervous system. There is growing interest in investigating the potential diagnostic and therapeutic utility of OXA in PD. To date, studies have reported a wide range of OXA concentrations in patients with PD. In this review, we discuss the current understanding of the dysregulation of OXA in PD and analyze its levels in the CSF.

العلاقة: https://doi.org/10.1016/j.clineuro.2024.108320Test; https://pubmed.ncbi.nlm.nih.gov/38781804Test

الإتاحة: https://doi.org/10.1016/j.clineuro.2024.108320Test
https://pubmed.ncbi.nlm.nih.gov/38781804Test

المؤلفون: Couvineau, Alain, Voisin, Thierry, Nicole, Pascal, Gratio, Valerie, Blais, Anne

المساهمون: Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

المصدر: ISSN: 1007-9327 ; World Journal of Gastroenterology ; https://agroparistech.hal.science/hal-04355985Test ; World Journal of Gastroenterology, 2021, 27, pp.7582 - 7596. ⟨10.3748/wjg.v27.i44.7582⟩.

مصطلحات موضوعية: Alain Couvineau 0000-0003-2912-5168 Thierry Voisin 0000-0002-4320-5183 Pascal Nicole 0000-0002-0004-616X Valerie Gratio 0000-0001-8563-3293 Anne Blais 0000-0002-0897-7612 Invited article Externally peer reviewed Peer-review report's scientific quality classification Grade A (Excellent): 0 Grade B (Very good): 0 Orexin Neuropeptide G-protein coupled receptor superfamily Inflammation Metabolic syndrome Cancer, Alain Couvineau 0000-0003-2912-5168, Thierry Voisin 0000-0002-4320-5183, Pascal Nicole 0000-0002-0004-616X, Valerie Gratio 0000-0001-8563-3293, Anne Blais 0000-0002-0897-7612 Invited article, Externally peer reviewed Peer-review report's scientific quality classification Grade A (Excellent): 0 Grade B (Very good): 0 Orexin, Neuropeptide, G-protein coupled receptor superfamily, Inflammation, Metabolic syndrome, Cancer, [SDV]Life Sciences [q-bio]

الوصف: Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system. These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation, intestinal motility, hormone secretion, lipolyze and reproduction functions. Associated to these peripheral functions, it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation, metabolic syndrome and cancers. The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease, multiple sclerosis and septic shock, obesity and digestive cancers.

العلاقة: hal-04355985; https://agroparistech.hal.science/hal-04355985Test; https://agroparistech.hal.science/hal-04355985/documentTest; https://agroparistech.hal.science/hal-04355985/file/Orexins%20A%20promising%20target%20to%20digestive%20cancers,%20inflammation,.pdfTest

الإتاحة: https://doi.org/10.3748/wjg.v27.i44.7582Test
https://agroparistech.hal.science/hal-04355985Test
https://agroparistech.hal.science/hal-04355985/documentTest
https://agroparistech.hal.science/hal-04355985/file/Orexins%20A%20promising%20target%20to%20digestive%20cancers,%20inflammation,.pdfTest

المؤلفون: Aegidius, Helene M., Kruse, Lars, Christensen, Gitte L., Lorentzen, Marc P., Jorgensen, Niklas R., Moresco, Monica, Pizza, Fabio, Plazzi, Giuseppe, Jennum, Poul J., Kornum, Birgitte R.

المصدر: Aegidius , H M , Kruse , L , Christensen , G L , Lorentzen , M P , Jorgensen , N R , Moresco , M , Pizza , F , Plazzi , G , Jennum , P J & Kornum , B R 2021 , ' Pre-treatment of blood samples reveal normal blood hypocretin/orexin signal in narcolepsy type I ' , Brain Communications , vol. 3 , no. 2 , 050 . https://doi.org/10.1093/braincomms/fcab050Test

مصطلحات موضوعية: hypocretin, orexin, plasma hypocretin-1, narcolepsy type 1, radioimmunoassay, PLASMA OREXIN-A, EXPRESSION, RECEPTORS, NEURONS, NEUROPEPTIDE, LEPTIN, CELLS

الوصف: The hypocretin/orexin system regulates arousal through central nervous system mechanisms and plays an important role in sleep, wakefulness and energy homeostasis. It is unclear whether hypocretin peptides are also present in blood due to difficulties in measuring reliable and reproducible levels of the peptides in blood samples. Lack of hypocretin signalling causes the sleep disorder narcolepsy type 1, and low concentration of cerebrospinal fluid hypocretin-l/oreadn-A peptide is a hallmark of the disease. This measurement has high diagnostic value, but performing a lumbar puncture is not without discomfort and possible complications for the patient. A blood-based test to assess hypocretin-1 deficiency would therefore be of obvious benefit. We here demonstrate that heating plasma or scrum samples to 65 degrees C for 30 min at pH 8 significantly increases hypocretin-1 immunoreactivity enabling stable and reproducible measurement of hypocretin-1 in blood samples. Specificity of the signal was verified by high-performance liquid chromatography and by measuring blood samples from mice lacking hypocretin. Unspecific background signal in the assay was high. Using our method, we show that hypocretin-1 immunoreactivity in blood samples from narcolepsy type 1 patients does not differ from the levels detected in control samples. The data presented here suggest that hypocretin-1 is present in the blood stream in the low picograms per millilitres range and that peripheral hypocretin-1 concentrations are unchanged in narcolepsy type 1.

وصف الملف: application/pdf

الإتاحة: https://doi.org/10.1093/braincomms/fcab050Test
https://curis.ku.dk/portal/da/publications/pretreatment-of-blood-samples-reveal-normal-blood-hypocretinorexin-signal-in-narcolepsy-type-iTest(a9b43a32-b29f-45a6-b819-b63589930fcc).html
https://curis.ku.dk/ws/files/273811422/Pre_treatment_of_blood_samples_reveal_normal_blood_hypocretin_orexin_signal_in_narcolepsy_type_1.pdfTest

المؤلفون: Davies, Julie

المساهمون: Karteris, M.

مصطلحات موضوعية: 616.8, Alzheimers disease, Orexin, Neuropeptide, Neurology

الوصف: Alzheimer’s disease (AD) is a neurodegenerative disease which affects over 500,000 people in the UK. Worldwide 44 million people are affected by AD and other dementias. Most cases occur over the age of 65 and is characterised by gradual and increasing loss of cognitive function and behavioural abnormalities. The main causes are a build-up of the toxic protein amyloid-β (Aβ) and hyperphosphorylation of the microtubule stabilising protein: tau, leading to neurofibrillary tangles (NFT). These two hallmarks of disease result in neuronal damage and cell death causing associated symptoms and eventually death. Orexins (OX) are neuropeptides which function to regulate the sleep-wake cycle and feeding behaviour. They are produced from a prepro-orexin (PPO) molecule and cleaved into two isoforms: orexin-A (OXA) and orexin-B (OXB). OXA and OXB are the ligands for two G-protein coupled receptors (GPCR): orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R). 50-80,000 OX producing neurons project to many areas of the brain including the lateral hypothalamus (LHA), locus coeruleus (LC), tuberomammillary nucleus (TMN), paraventricular nucleus (PVN) and raphe nuclei and from these areas regulate feeding and appetite and the sleep wake cycle through their receptors. QRFP is a newly discovered neuropeptide which exerts similar orexigenic activity including the control of feeding behaviour. It is the ligand for the GPCR GPR103, both of which are widely expressed in the brain and also in the retina, testes, thyroid, pituitary and prostate. GPR103 also shares 48 and 47% protein sequence homology with OX1R and OX2R respectively. It is in these tissues where it can exert other physiological functions including regulation of feeding, control of the gonadotropic axis and bone formation. The exact expression and signalling characteristics and physiological actions of QRFP/GPR103 are still poorly understood. It is through the physiological functions of the orexigenic system and the clinical symptoms observed in AD which suggests a possible link between the two. For example, in AD one of the main reasons for institutionalisation is the severely dysregulated sleep pattern that is experienced by sufferers. They experience increased nocturnal activity and early awakenings as well as hypersomnia and excessive daytime sleepiness; all of which is beyond what someone of the same age experiences. As well as this AD patients suffer from significant weight loss and a significant negative correlation has been identified between progression of disease and appetite. All of this points towards an involvement of the orexigenic system in AD. AD patients have been found to have a 40% loss of immunoreactive OX neurons and have severe reductions in circulating OXA. This led us to believe that the OX system is of vital importance in AD and could be targeted to ameliorate symptoms. Studies have implicated OX and OXR in memory processes, appetite regulation, and severe disturbances of the sleep-wake cycle all of which are phenotypes of AD. Given that they play a key role in energy homeostasis and physiological behaviour, we hypothesise that OXs and their receptors are implicated in the pathophysiology of AD. Therefore, in this study we will investigate the detailed expression and signalling characteristics of OXR and GPR103 in vitro and in clinical samples In this study we neuronally differentiated two human neuroblastoma cell lines: IMR32 and SH-SY5Y. Neuronally acquired phenotype was confirmed through increased neurite length, increased expression of key neuronal proteins and increases in microtubule-associated protein tau (MAPT), neurogenin1 (NG1) and neuron-specific enolase (NSE) as well as a reduction in the neuronal marker of immaturity; nestin (NES). OXR and GPR103 were confirmed in both cell lines after differentiation at mRNA and protein level and were shown to be fully functional through phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2). We also identified possible cross talk of GPR103 with the OXR though addition of selective OXR antagonists, which blocked QRFP induced ERK1/2 phosphorylation. We show for the first time that addition of Aβ42 and zinc sulphate to mimic AD in vitro, results in a significant reduction of OX1R and GPR103 in the cell lines SH-SY5Y and we have performed the first comprehensive study in clinical AD patients which demonstrate a loss of OX1R, OX2R and GPR103 at mRNA and protein level compared to age matched controls in the hippocampus. We performed microarray analysis which identified many genes and pathways regulated by the OXA, OXB and QRFP; including corticotropin-releasing hormone receptor (CRHR1), regulated in development and DNA damage responses 1 (REDD1), erythropoietin (EPO), Bcl-2-like protein 1 (BCL2L11), myb proto-oncogene protein (c-myb), vasoactive intestinal peptide (VIP), endothelin 1 (EDN1) as well as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) and hypoxia-inducible factor-1α (HIF-1α) pathways. These genes are all implicated in neuroprotection, particularly in AD. This represents the first comprehensive gene expression data in a neuroblastoma cell line for these orexigenic proteins. Collectively these data suggest a potential role of the orexigenic system in neuroprotection and a functional loss of the receptors in AD patients which could confer a loss of neuroprotection through the orexigenic system. Pharmacological intervention directed at the orexigenic system may prove to be an attractive avenue towards the discovery of novel therapeutics for diseases such as AD and improving neuroprotective signalling pathways.

الوصول الحر: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.629959Test

المؤلفون: Lee M. T., Chiu Y. -T., Chiu Y. -C., Hor C. C., Lee H. -J., Guerrini R., Calo' G., Chiou L. -C.

المساهمون: Lee, M. T., Chiu, Y. -T., Chiu, Y. -C., Hor, C. C., Lee, H. -J., Guerrini, R., Calo', G., Chiou, L. -C.

مصطلحات موضوعية: Endocannabinoid, Metabotropic glutamate receptor, Neuropeptide S, Orexin, Periaqueductal gray, Substance P, Animal, Male, Mice, Neuropeptide, Orexin Receptor, Receptor, Cannabinoid, CB1, Metabotropic Glutamate 5, Stress, Psychological, Ventral Thalamic Nuclei, Analgesia

الوصف: Background: Stress-induced analgesia (SIA) is an evolutionarily conserved phenomenon during stress. Neuropeptide S (NPS), orexins, substance P, glutamate and endocannabinoids are known to be involved in stress and/or SIA, however their causal links remain unclear. Here, we reveal an unprecedented sequential cascade involving these mediators in the lateral hypothalamus (LH) and ventrolateral periaqueductal gray (vlPAG) using a restraint stress-induced SIA model. Methods: Male C57BL/6 mice of 8-12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice. Results: NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice. Conclusions: These results suggest that, during stress, NPS is released and ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/31915019; info:eu-repo/semantics/altIdentifier/wos/WOS:000512121200001; volume:27; issue:1; firstpage:1; lastpage:15; numberofpages:15; journal:JOURNAL OF BIOMEDICAL SCIENCE; http://hdl.handle.net/11577/3386670Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85077704312

الإتاحة: https://doi.org/10.1186/s12929-019-0590-1Test
http://hdl.handle.net/11577/3386670Test

المؤلفون: Cristina Concetti, Denis Burdakov

المصدر: Frontiers in Neuroscience, Vol 15 (2021)

مصطلحات موضوعية: hypothalamus, neuropeptide, orexin, melanin-concentrating hormone, memory, locomotion, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: The lateral hypothalamus (LH) is classically implicated in sleep-wake control. It is the main source of orexin/hypocretin and melanin-concentrating hormone (MCH) neuropeptides in the brain, which have been both implicated in arousal state switching. These neuropeptides are produced by non-overlapping LH neurons, which both project widely throughout the brain, where release of orexin and MCH activates specific postsynaptic G-protein-coupled receptors. Optogenetic manipulations of orexin and MCH neurons during sleep indicate that they promote awakening and REM sleep, respectively. However, recordings from orexin and MCH neurons in awake, moving animals suggest that they also act outside sleep/wake switching. Here, we review recent studies showing that both orexin and MCH neurons can rapidly (sub-second-timescale) change their firing when awake animals experience external stimuli, or during self-paced exploration of objects and places. However, the sensory-behavioral correlates of orexin and MCH neural activation can be quite different. Orexin neurons are generally more dynamic, with about 2/3rds of them activated before and during self-initiated running, and most activated by sensory stimulation across sensory modalities. MCH neurons are activated in a more select manner, for example upon self-paced investigation of novel objects and by certain other novel stimuli. We discuss optogenetic and chemogenetic manipulations of orexin and MCH neurons, which combined with pharmacological blockade of orexin and MCH receptors, imply that these rapid LH dynamics shape fundamental cognitive and motor processes due to orexin and MCH neuropeptide actions in the awake brain. Finally, we contemplate whether the awake control of psychomotor brain functions by orexin and MCH are distinct from their “arousal” effects.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fnins.2021.639313/fullTest; https://doaj.org/toc/1662-453XTest

الوصول الحر: https://doaj.org/article/5376bcba43cf4c9e824ae130603c1686Test

المؤلفون: Laurine Becquet, Catalina Abad, Mathilde Leclercq, Camille Miel, Laetitia Jean, Gaëtan Riou, Alain Couvineau, Olivier Boyer, Yossan-Var Tan

المصدر: Journal of Neuroinflammation, Vol 16, Iss 1, Pp 1-12 (2019)

مصطلحات موضوعية: Orexin A, Neuropeptide, Neuro-immunomodulation, Multiple sclerosis, EAE, Neuroinflammation, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background Orexins (hypocretins, Hcrt) A and B are GPCR-binding hypothalamic neuropeptides known to regulate sleep/wake states and feeding behavior. A few studies have shown that orexin A exhibits anti-inflammatory and neuroprotective properties, suggesting that it might provide therapeutic effects in inflammatory and neurodegenerative diseases like multiple sclerosis (MS). In MS, encephalitogenic Th1 and Th17 cells trigger an inflammatory response in the CNS destroying the myelin sheath. Here, we investigated the effects of peripheral orexin A administration to mice undergoing experimental autoimmune encephalomyelitis (EAE), a widely used model of MS. Methods Mice were subcutaneously immunized with myelin oligodendrocyte glycoprotein peptide (MOG)35–55 in CFA. Mice were treated intraperitoneally for five consecutive days with either PBS or 300 μg of orexin A starting at a moderate EAE score. Molecular, cellular, and histological analysis were performed by real-time PCR, ELISA, flow cytometry, and immunofluorescence. Results Orexin A strongly ameliorated ongoing EAE, limiting the infiltration of pathogenic CD4+ T lymphocytes, and diminishing chemokine (MCP-1/CCL2 and IP-10/CXCL10) and cytokine (IFN-γ (Th1), IL-17 (Th17), TNF-α, IL-10, and TGF-β) expressions in the CNS. Moreover, orexin A treatment was neuroprotective, decreasing demyelination, astrogliosis, and microglial activation. Despite its strong local therapeutic effects, orexin A did not impair peripheral draining lymph node cell proliferation and Th1/Th17 cytokine production in response to MOG35–55 in vitro. Conclusions Peripherally-administered orexin A ameliorated EAE by reducing CNS neuroinflammation. These results suggest that orexins may represent new therapeutic candidates that should be further investigated for MS treatment.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12974-019-1447-yTest; https://doaj.org/toc/1742-2094Test

الوصول الحر: https://doaj.org/article/69e7f6833b604226b92795a7fa86ab95Test

المؤلفون: Concetti, Cristina, id_orcid:0 000-0002-9755-3298, Burdakov, Denis

المصدر: Frontiers in Neuroscience, 15

مصطلحات موضوعية: Hypothalamus, Neuropeptide, Orexin, Melanin-concentrating hormone, Memory, Locomotion

الوصف: The lateral hypothalamus (LH) is classically implicated in sleep-wake control. It is the main source of orexin/hypocretin and melanin-concentrating hormone (MCH) neuropeptides in the brain, which have been both implicated in arousal state switching. These neuropeptides are produced by non-overlapping LH neurons, which both project widely throughout the brain, where release of orexin and MCH activates specific postsynaptic G-protein-coupled receptors. Optogenetic manipulations of orexin and MCH neurons during sleep indicate that they promote awakening and REM sleep, respectively. However, recordings from orexin and MCH neurons in awake, moving animals suggest that they also act outside sleep/wake switching. Here, we review recent studies showing that both orexin and MCH neurons can rapidly (sub-second-timescale) change their firing when awake animals experience external stimuli, or during self-paced exploration of objects and places. However, the sensory-behavioral correlates of orexin and MCH neural activation can be quite different. Orexin neurons are generally more dynamic, with about 2/3rds of them activated before and during self-initiated running, and most activated by sensory stimulation across sensory modalities. MCH neurons are activated in a more select manner, for example upon self-paced investigation of novel objects and by certain other novel stimuli. We discuss optogenetic and chemogenetic manipulations of orexin and MCH neurons, which combined with pharmacological blockade of orexin and MCH receptors, imply that these rapid LH dynamics shape fundamental cognitive and motor processes due to orexin and MCH neuropeptide actions in the awake brain. Finally, we contemplate whether the awake control of psychomotor brain functions by orexin and MCH are distinct from their “arousal” effects. ; ISSN:1662-453X ; ISSN:1662-4548

وصف الملف: application/application/pdf

العلاقة: info:eu-repo/semantics/altIdentifier/wos/000636665300001; http://hdl.handle.net/20.500.11850/478114Test

الإتاحة: https://doi.org/20.500.11850/478114Test
https://doi.org/10.3929/ethz-b-000478114Test
https://doi.org/10.3389/fnins.2021.639313Test
https://hdl.handle.net/20.500.11850/478114Test