Elucidating the origin of expiratory abdominal activity during sleep and analysis of its manifestation in conditions of an impaired inspiratory drive

• Author / Creator

  Pisanski, Annette

• This dissertation explored respiratory control mechanisms during sleep, with a specific focus on the contribution of the lateral parafacial area (pFL) to the generation of abdominal recruitment. Existing theories posit the preBötzinger complex (preBötC) as the inspiratory oscillator and identify the pFL as the driver of active expiration through abdominal muscle (ABD) recruitment. Despite induced muscle paralysis during REM sleep, ABD recruitment persists, exhibiting correlations with heightened tidal volume and the regularization of respiratory periods. Utilizing chemogenetic modulation of the pFL activity, this study revealed a state-dependent impact: inhibiting the pFL reduced REM events expressing ABD recruitment, while activation increased both the frequency and intensity of such events. Intriguingly, ABD recruitment during NREM sleep and wakefulness remained unaffected. Additionally, this thesis investigated the rostrocaudal localization of the pFL core, addressing the variability in prior studies regarding the pFL response coordinates. Through the measurement of the impact of GABAergic disinhibition on respiration at distinct rostro-caudal sites, this study identified that more rostral pFL locations are pivotal for substantial and enduring changes in ABD recruitment and respiratory responses. Moreover, this dissertation explored the occurrence of ABD recruitment in sleep-disordered breathing (SDB), a health concern with cardio-metabolic implications. By leveraging the Kappa-opioid-receptor-DREADD (KORD) system to depress preBötzinger complex activity in rats, this study observed heightened respiratory disturbances and ABD recruitment during REM sleep following KORD receptor ligand administration. These findings offer valuable insights into the role of the pFL in sleep-related respiratory control, elucidating state-dependent mechanisms and identifying potential therapeutic targets for sleep-related breathing disorders.

• Subjects / Keywords

  • active expiration
  • sleep disordered breathing
  • sleep apnea
  • breathing
  • pFL
  • preBötC

• Graduation date

  Spring 2024

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-b3e2-6d24

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.