Exploring the role of the Kölliker–Fuse nucleus in breathing variability by mathematical modelling

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversity of Pittsburgh-
Autor(es): dc.contributorIndiana University Purdue University Indianapolis-
Autor(es): dc.contributorUniversity of Bristol-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorGeorgia State University-
Autor(es): dc.creatorJohn, S. R.-
Autor(es): dc.creatorBarnett, W. H.-
Autor(es): dc.creatorAbdala, A. P.L.-
Autor(es): dc.creatorZoccal, D. B.-
Autor(es): dc.creatorRubin, J. E.-
Autor(es): dc.creatorMolkov, Y. I.-
Data de aceite: dc.date.accessioned2025-08-21T15:28:57Z-
Data de disponibilização: dc.date.available2025-08-21T15:28:57Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1113/JP285158-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/306458-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/306458-
Descrição: dc.descriptionAbstract: The Kölliker–Fuse 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-like breathing phenotypes. Using nullcline analysis, we identify the types of inhibitory inputs to the KF leading to RTT-like respiratory patterns and suggest possible KF local circuit organizations. When the identified properties are present, the two models also exhibit quantal acceleration of late-expiratory 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. (Figure presented.). Key points: The Kölliker–Fuse nucleus (KF), a part of the parabrachial complex, is involved in regulating normal breathing and controlling active abdominal expiration during increased ventilation. 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. By analysing different model configurations, the study identifies inhibitory inputs to the KF that lead to RTT-like respiratory patterns and proposes potential KF local circuit organizations. Two models are presented that simulate both normal breathing and RTT-like breathing patterns. These models provide testable hypotheses and specific predictions for future experimental investigations, offering a general framework for understanding KF dynamics and potential network interactions.-
Descrição: dc.descriptionGeorgia State University-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionNational Science Foundation-
Descrição: dc.descriptionNational Center for Complementary and Integrative Health-
Descrição: dc.descriptionUniversity of Pittsburgh-
Descrição: dc.descriptionIndiana University Purdue University Indianapolis-
Descrição: dc.descriptionUniversity of Bristol-
Descrição: dc.descriptionSão Paulo State University-
Descrição: dc.descriptionGeorgia State University-
Descrição: dc.descriptionSão Paulo State University-
Descrição: dc.descriptionCNPq: 303481/2021-8-
Descrição: dc.descriptionNational Science Foundation: DMS 1951095-
Descrição: dc.descriptionNational Center for Complementary and Integrative Health: R01AT008632-
Formato: dc.format93-112-
Idioma: dc.languageen-
Relação: dc.relationJournal of Physiology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectcontrol of breathing-
Palavras-chave: dc.subjectKölliker–Fuse-
Palavras-chave: dc.subjectmodelling-
Palavras-chave: dc.subjectRett syndrome-
Título: dc.titleExploring the role of the Kölliker–Fuse nucleus in breathing variability by mathematical modelling-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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