A6 neurons simultaneously modulate active expiration and upper airway resistance in rats

Author(s)

Magalhaes, Karolyne S. ^[1] ; de Britto, Alan A. ^[1] ; Paton, Julian F. R. ^[2] ; Moraes, Davi J. A. ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Physiol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, Cardiovasc Auton Res Cluster, Auckland - New Zealand

• Document type: Journal article
• Source: Experimental Physiology; v. 105, n. 1, p. 53-64, JAN 2020.
• Web of Science Citations: 1

Abstract

New Findings What is the central question of this study?Do A6 neurons modulate active expiratory and airway responses evoked by hypercapnia/acidosis? What is the main finding and its importance?Acute inhibition of A6 neurons reduced active expiratory, inspiratory and the associated oropharyngeal and laryngeal motor responses to hypercapnia/acidosis. A6 neurons provide excitatory synaptic drive contributing to the central generation of inspiratory and expiratory motor activity as well as the control of upper airway resistance. During rest, inspiration is an active phenomenon, whereas expiration is passive. Under conditions of high chemical drive, such as hypercapnia/acidosis, there is an increase in inspiratory activity, expiration becomes active and upper airway resistance is reduced. The locus coeruleus noradrenergic neurons (A6 neurons) are activated when exposed to elevated CO2/{[}H+] levels and modulate respiratory brainstem neurons regulating ventilation. However, the role of A6 neurons in the control of upper airway resistance is not fully understood. We tested the hypothesis that A6 neurons contribute to the central generation of active inspiratory and expiratory responses and the associated changes in the motor nerves controlling upper airway resistance during hypercapnia/acidosis in rats. Using a perfused brainstem-spinal cord preparation, we inhibited A6 neurons using pharmacogenetics and evaluated the active expiratory (abdominal nerve), laryngeal (cervical vagus nerve), oropharyngeal (hypoglossal nerve) and inspiratory (phrenic nerve) motor nerve responses to hypercapnia/acidosis. Acute inhibition of A6 neurons did not produce significant changes in the respiratory pattern in normocapnia. However, the hypercapnia/acidosis-induced active expiratory response and the associated changes in the motor nerves responsible for control of oropharyngeal and laryngeal resistance, as well as the inspiratory response were all reduced after inhibition of A6 neurons. Our data demonstrate that A6 neurons exert an important excitatory synaptic drive to the central generation of both active inspiratory and expiratory activities and modulate the control of upper airway resistance during hypercapnia/acidosis. (AU)

• FAPESP's process: 17/09071-9 - Participation of the noradrenergic neurons of locus coeruleus in the central generation of inspiratory and expiratory activities in response to the activation of the central chemoreceptors of rats
• Grantee: Karolyne Silva Magalhães
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/24994-3 - Participation of parafacial respiratory group in the orofacial and nasofacial motor responses of rats induced by activation of peripheral and central chemoreceptors
• Grantee: Alan Andrade de Britto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/10484-5 - Electrophysiological and molecular characterization of neurons involved in the generation of respiratory rhythm and pattern of rats during postnatal development
• Grantee: Davi José de Almeida Moraes
• Support Opportunities: Research Grants - Young Investigators Grants