{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:14:16Z","timestamp":1778904856796,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:00:00Z","timestamp":1733616000000},"content-version":"am","delay-in-days":366,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008545","name":"Georgia State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["303481\/2021\u20108"],"award-info":[{"award-number":["303481\/2021\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DMS 1951095"],"award-info":[{"award-number":["DMS 1951095"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R01AT008632"],"award-info":[{"award-number":["R01AT008632"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>The K\u00f6lliker\u2013Fuse nucleus (KF), which is part of the parabrachial complex, participates in the generation of eupnoea under resting conditions and the control of active abdominal expiration when increased ventilation is required. Moreover, dysfunctions in KF neuronal activity are believed to play a role in the emergence of respiratory abnormalities seen in Rett syndrome (RTT), a progressive neurodevelopmental disorder associated with an irregular breathing pattern and frequent apnoeas. Relatively little is known, however, about the intrinsic dynamics of neurons within the KF and how their synaptic connections affect breathing pattern control and contribute to breathing irregularities. In this study, we use a reduced computational model to consider several dynamical regimes of KF activity paired with different input sources to determine which combinations are compatible with known experimental observations. We further build on these findings to identify possible interactions between the KF and other components of the respiratory neural circuitry. Specifically, we present two models that both simulate eupnoeic as well as RTT\u2010like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT\u2010like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late\u2010expiratory activity, a hallmark of active expiration featuring forced exhalation, with increasing inhibition to KF, as reported experimentally. Hence, these models instantiate plausible hypotheses about possible KF dynamics and forms of local network interactions, thus providing a general framework as well as specific predictions for future experimental testing.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15855-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The K\u00f6lliker\u2013Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dysfunction in KF neuronal activity is thought to contribute to respiratory abnormalities seen in Rett syndrome (RTT). This study utilizes computational modelling to explore different dynamical regimes of KF activity and their compatibility with experimental observations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT\u2010like respiratory patterns and proposes potential KF local circuit organizations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Two models are presented that simulate both normal breathing and RTT\u2010like breathing patterns.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285158","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T16:34:25Z","timestamp":1702053265000},"page":"93-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the role of the K\u00f6lliker\u2013Fuse nucleus in breathing variability by mathematical modelling"],"prefix":"10.1113","volume":"602","author":[{"given":"S. R.","family":"John","sequence":"first","affiliation":[{"name":"University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. H.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Indiana University Purdue University Indianapolis  Indianapolis IN USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6566-9205","authenticated-orcid":false,"given":"A. P. L.","family":"Abdala","sequence":"additional","affiliation":[{"name":"University of Bristol  Bristol UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0369-5907","authenticated-orcid":false,"given":"D. B.","family":"Zoccal","sequence":"additional","affiliation":[{"name":"S\u00e3o Paulo State University  Araraquara Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1513-1551","authenticated-orcid":false,"given":"J. 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