title: Late-expiratory activity: emergence and interactions with the respiratory CpG.
abstract: The respiratory rhythm and motor pattern are hypothesized to be generated by a brain stem respiratory network with a rhythmogenic core consisting of neural populations interacting within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes and controlled by drives from other brain stem compartments. Our previous large-scale computational model reproduced the behavior of this network under many different conditions but did not consider neural oscillations that were proposed to emerge within the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) and drive preinspiratory (or late-expiratory, late-E) discharges in the abdominal motor output. Here we extend the analysis of our previously published data and consider new data on the generation of abdominal late-E activity as the basis for extending our computational model. The extended model incorporates an additional late-E population in RTN/pFRG, representing a source of late-E oscillatory activity. In the proposed model, under normal metabolic conditions, this RTN/pFRG oscillator is inhibited by BötC/pre-BötC circuits, and the late-E oscillations can be released by either hypercapnia-evoked activation of RTN/pFRG or by hypoxia-dependent suppression of RTN/pFRG inhibition by BötC/pre-BötC. The proposed interactions between BötC/pre-BötC and RTN/pFRG allow the model to reproduce several experimentally observed behaviors, including quantal acceleration of abdominal late-E oscillations with progressive hypercapnia and quantal slowing of phrenic activity with progressive suppression of pre-BötC excitability, as well as to predict a release of late-E oscillations by disinhibition of RTN/pFRG under normal conditions. The extended model proposes mechanistic explanations for the emergence of RTN/pFRG oscillations and their interaction with the brain stem respiratory network.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Yaroslav I
authors.initials: YI
authors.lastname: Molkov
authors.forename: Ana P L
authors.initials: AP
authors.lastname: Abdala
authors.forename: Bartholomew J
authors.initials: BJ
authors.lastname: Bacak
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Smith
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
authors.forename: Ilya A
authors.initials: IA
authors.lastname: Rybak
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045853:Exhalation / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012119:Respiration / Q000187:drug effects; D019782:Riluzole / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole