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Previous research has demonstrated that the absence of orexin (Orx) can trigger narcolepsy, a condition characterized by frequent shifts between wakefulness and sleep. However, the specific mechanisms and temporal patterns through which Orx regulates wakefulness\/sleep are not fully understood. In this study, we developed a new model that combines the classical Phillips\u2013Robinson sleep model with the Orx network. Our model incorporates a recently discovered indirect inhibition of Orx on sleep-promoting neurons in the ventrolateral preoptic nucleus. By integrating appropriate physiological parameters, our model successfully replicated the dynamic behavior of normal sleep under the influence of circadian drive and homeostatic processes. Furthermore, our results from the new sleep model unveiled two distinct effects of Orx: excitation of wake-active neurons and inhibition of sleep-active neurons. The excitation effect helps to sustain wakefulness, while the inhibition effect contributes to arousal, consistent with experimental findings [De Luca et al., Nat. Commun. 13, 4163 (2022)]. Moreover, we utilized the theory of potential landscapes to investigate the physical mechanisms underlying the frequent transitions observed in narcolepsy. The topography of the underlying landscape delineated the brain\u2019s capacity to transition between different states. Additionally, we examined the impact of Orx on barrier height. Our analysis demonstrated that a reduced level of Orx led to a bistable state with an extremely low threshold, contributing to the development of narcoleptic sleep disorder.<\/jats:p>","DOI":"10.1063\/5.0156090","type":"journal-article","created":{"date-parts":[[2023,7,8]],"date-time":"2023-07-08T04:42:45Z","timestamp":1688791365000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["A physical understanding and quantification for the regulation of orexin on sleep"],"prefix":"10.1063","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-362X","authenticated-orcid":false,"given":"Chenggui","family":"Yao","sequence":"first","affiliation":[{"name":"College of Data Science, Jiaxing University 1 , Jiaxing 314000, China"},{"name":"Research Center for Augmented Intelligence, Research Institute of Artificial Intelligence, Zhejiang Lab 2 , Hangzhou, Zhejiang 311101, China"},{"name":"Wenzhou Key Laboratory of Biophysics, Wenzhou Institute, University of Chinese Academy of Sciences 3 , Wenzhou 325000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Physics, Xiamen University 4 , Xiamen 361005, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangdong","family":"Tang","sequence":"additional","affiliation":[{"name":"Sleep Medicine Center, Mental Health Center, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University 5 , Chengdu 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0683-0270","authenticated-orcid":false,"given":"Wei","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Mathematical Sciences, South China Normal University 6 , Guangzhou 510631, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongping","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center for Augmented Intelligence, Research Institute of Artificial Intelligence, Zhejiang Lab 2 , Hangzhou, Zhejiang 311101, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-0544","authenticated-orcid":false,"given":"Jianwei","family":"Shuai","sequence":"additional","affiliation":[{"name":"Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), and Wenzhou Institute, University of Chinese Academy of Sciences 7 , Wenzhou, Zhejiang 325001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"317","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"2023070804424020800_c1","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","volume":"92","year":"1998","journal-title":"Cell"},{"key":"2023070804424020800_c2","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1073\/pnas.95.1.322","volume":"95","year":"1998","journal-title":"Proc. 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