title: Functional connectivity in raphé-pontomedullary circuits supports active suppression of breathing during hypocapnic apnea.
abstract: Hyperventilation is a common feature of disordered breathing. Apnea ensues if CO2 drive is sufficiently reduced. We tested the hypothesis that medullary raphé, ventral respiratory column (VRC), and pontine neurons have functional connectivity and persistent or evoked activities appropriate for roles in the suppression of drive and rhythm during hyperventilation and apnea. Phrenic nerve activity, arterial blood pressure, end-tidal CO2, and other parameters were monitored in 10 decerebrate, vagotomized, neuromuscularly-blocked, and artificially ventilated cats. Multielectrode arrays recorded spiking activity of 649 neurons. Loss and return of rhythmic activity during passive hyperventilation to apnea were identified with the S-transform. Diverse fluctuating activity patterns were recorded in the raphé-pontomedullary respiratory network during the transition to hypocapnic apnea. The firing rates of 160 neurons increased during apnea; the rates of 241 others decreased or stopped. VRC inspiratory neurons were usually the last to cease firing or lose rhythmic activity during the transition to apnea. Mayer wave-related oscillations (0.04-0.1 Hz) in firing rate were also disrupted during apnea. Four-hundred neurons (62%) were elements of pairs with at least one hyperventilation-responsive neuron and a correlational signature of interaction identified by cross-correlation or gravitational clustering. Our results support a model with distinct groups of chemoresponsive raphé neurons contributing to hypocapnic apnea through parallel processes that incorporate disfacilitation and active inhibition of inspiratory motor drive by expiratory neurons. During apnea, carotid chemoreceptors can evoke rhythm reemergence and an inspiratory shift in the balance of reciprocal inhibition via suppression of ongoing tonic expiratory neuron activity.
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Nuding
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Segers
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Iceman
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Russell
authors.initials: R
authors.lastname: O'Connor
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Jay B
authors.initials: JB
authors.lastname: Dean
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida; and.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Bolser
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida; and.
authors.forename: David M
authors.initials: DM
authors.lastname: Baekey
authors.affiliation: Departments of Medicine and Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Dick
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Roger
authors.initials: R
authors.lastname: Shannon
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida;
authors.forename: Kendall F
authors.initials: KF
authors.lastname: Morris
authors.affiliation: Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida; blindsey@health.usf.edu.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Lindsey
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001049:Apnea / Q000503:physiopathology*; D002415:Cats; D004567:Electrodes, Implanted; D016857:Hypocapnia / Q000503:physiopathology*; D008526:Medulla Oblongata / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D011149:Pons / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000503:physiopathology*; D012119:Respiration; D012121:Respiration, Artificial
keywords: apnea; brainstem; breathing; hyperventilation; network