title: Rhythmic bursting of pre- and post-inspiratory neurones during central apnoea in mature mice.
abstract: 1. Stimulation of pulmonary vagal C fibres (PCFs) inhibits inspiration but the response pattern of respiratory rhythm-generating neurones is unknown. This study provides the first description of the effects of PCF stimulation on six different types of respiratory neurones located in the ventrolateral medulla of the mature mouse. 2. Studies were performed in both urethane-anaesthetized (1.5 g kg-1 I.P.) mature mice and in an arterially perfused working heart-brainstem preparation (WHBP). In both preparations the respiratory motor pattern of phrenic and recurrent laryngeal nerves were comparable. Stimulation of PCFs, using phenylbiguanide (2-5 micrograms) injected into the right atrium, evoked a similar respiratory and cardiac response pattern in both anaesthetized and perfused mice, which included: (i) a significant prolongation of the inter-inspiratory interval; (ii) an increase in the duration and amplitude of post-inspiratory (PI) activity; and (iii) an atropine-sensitive bradycardia (50-260 beats min-1). 3. In the WHBP, PCF stimulation evoked a depolarization (11 +/- 1 mV) and high frequency tonic discharge (up to 64 Hz) in ten out of twenty-one PI neurones. During the PCF-induced prolongation of PI activity all other PI neurones (n = 11), as well as pre-inspiratory neurones (PreI; n = 11), displayed oscillations in membrane potential and/or rhythmic bursting at a similar frequency of 0.7-1.0 Hz. Other respiratory neurones recorded, including stage II expiratory neurones (n = 7), early- (n = 6), ramp- (n = 16) and late-inspiratory neurones (n = 4), ceased firing rhythmically during PCF stimulation. 4. The firing behaviour of PI and PreI neurones was assessed after switching to a low Ca2+ (0.2 mM)-high Mg2+ (5.25 mM) perfusate to block synaptic transmission in the WHBP. In the absence of synaptic transmission, PreI neurones (n = 7/8) continued to discharge rhythmically, whereas all other respiratory cell types (including PI neurones, n = 5) fired tonically. 5. In conclusion, stimulation of PCFs elicits a reflex-evoked prolongation of the PI phase of the respiratory cycle and excitation of PI neurones including rhythmic discharging. It is suggested that this rhythmic bursting depends on inhibitory connections from PreI neurones. The functional significance of these central 'apnoeic rhythms' are discussed.
authors.affiliation: Department of Physiology, School of Medical Sciences, University of Bristol, UK. julian.f.r.paton@bris.ac.uk
authors.forename: J F
authors.initials: JF
authors.lastname: Paton
mesh_terms: D000367:Age Factors; D000758:Anesthesia; D000818:Animals; D001049:Apnea / Q000503:physiopathology*; D001933:Brain Stem / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002628:Chemoreceptor Cells / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D006321:Heart / Q000502:physiology; D008168:Lung / Q000294:innervation; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010507:Periodicity; D012119:Respiration / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology
chemical_list: D008274:Magnesium; D002118:Calcium