Skip to content

Reduced computational modelling of Kölliker-Fuse contributions to breathing patterns in Rett syndrome

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)2651-2672
Number of pages22
JournalJournal of Physiology
Volume597
Issue number10
Early online date16 Apr 2019
DOIs
DateAccepted/In press - 7 Mar 2019
DateE-pub ahead of print - 16 Apr 2019
DatePublished (current) - 15 May 2019

Abstract

Key points: Reduced computational models are used to test effects of loss of inhibition to the Kölliker-Fuse nucleus (KFn). Three reduced computational models that simulate eupnoeic and vagotomized respiratory rhythms are considered. All models exhibit the emergence of respiratory perturbations associated with Rett syndrome as inhibition to the KFn is diminished. Simulations suggest that application of 5-HT 1A agonists can mitigate the respiratory pathology. The three models can be distinguished and tested based on their predictions about connections and dynamics within the respiratory circuit and about effects of perturbations on certain respiratory neuron populations. Abstract: Rett syndrome (RTT) is a developmental disorder that can lead to respiratory disturbances featuring prolonged apnoeas of variable durations. Determining the mechanisms underlying these effects at the level of respiratory neural circuits would have significant implications for treatment efforts and would also enhance our understanding of respiratory rhythm generation and control. While experimental studies have suggested possible factors contributing to the respiratory patterns of RTT, we take a novel computational approach to the investigation of RTT, which allows for direct manipulation of selected system parameters and testing of specific hypotheses. Specifically, we present three reduced computational models, developed using an established framework, all of which successfully simulate respiratory outputs across eupnoeic and vagotomized conditions. All three models show that loss of inhibition to the Kölliker-Fuse nucleus reproduces the key respiratory alterations associated with RTT and, as suggested experimentally, that effects of 5-HT 1A agonists on the respiratory neural circuit suffice to alleviate this respiratory pathology. Each of the models makes distinct predictions regarding the neuronal populations and interactions underlying these effects, suggesting natural directions for future experimental testing.

    Research areas

  • breathing, computational model, inhibition, Kölliker-Fuse nucleus, Rett syndrome, serotonin

Documents

Documents

  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277592 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 3.58 MB, PDF document

    Embargo ends: 16/04/20

    Request copy

DOI

View research connections

Related faculties, schools or groups