Hering‐Breuer evoked regulation of respiratory rhythm variability in rats (686.25)

Abstract

Hering‐Breuer‐related afferent activity affects respiratory patterning in disparate ways: constant mechanical ventilation entrains the respiratory rhythm; yet removal of vagal feedback reduces respiratory rhythm variability. We hypothesize that these effects are mechanistically linked and test this hypothesis by closing the Hering Breuer Reflex feedback loop via rhythmic vagal nerve stimulation in situ before and after suppressing activity in the nucleus tractus solitarii (nTS) or Kölliker‐Fuse nuclei (KFn) by microinjection of muscimol, a GABAAR agonist. We measured feedback‐evoked entrainment of respiration and the variability of the rhythm in the presence or absence of periodic vagal feedback. Rhythmic vagal feedback evoked periods of entrainment interposed by phase slips. Analysis of respiratory rhythm variability revealed that vagal feedback amplified intrinsic respiratory rhythm variability via the transitions from a phase slip to stable entrainment. Suppressing nTS activity eliminated both entrainment and variability amplification. Suppressing KFn activity increased entrainment strength, reduced phase slip frequency and blunted variability amplification. We conclude that 1) Hering‐Breuer feedback inputs are sufficient to amplify respiratory variability via a noisy synchronization mechanism and 2) both entrainment and variability depend on KFn and nTS activity.Grant Funding Source: Supported by NS069220 and T32 HL007913