Activation of airway sensory nerves causes respiratory and autonomic reflexes. The majority of the sensory nerves are only sensitive to noxious stimuli, such as inflammation, infection, irritants and pollutants. Activation of these nociceptive sensory nerves evokes protective mechanisms such as apnea, cough and bradycardia that can contribute to disease morbidity. Airway nociceptive sensory nerves are heterogeneous with respect to gene expression and neuroanatomy, and our objective is to characterize the specific reflexes evoked by activation of specific afferent subsets. To selectively activate these vagal afferent subpopulations in vivo, mice were exposed to nebulized selective stimuli such as capsaicin (transient receptor potential (TRP) vanillin 1 (V1) agonist), allyl isothiocyanate (AITC, TRP ankyrin 1 (A1) agonist) and clozapine-N-oxide (CNO, selective agonist for the designer receptors exclusively activated by designer drugs (DREADD) stimulatory receptor hM3Dq). hM3Dq expression was selectively expressed in sensory subpopulations under the control of cre recombinase in TRPV1-cre (all nociceptors) and Tac1-cre (peptidergic nerves). ECGs were recorded via radiotelemetry following implantation of biopotential sensing modules, and respiration was measured via whole body plethysmography. Our data indicate that stimulation of nociceptive subpopulations selectively evokes bradypnea and bradycardia in freely moving wild type mice.
Support or Funding Information
This research is funded by the National Heart Lung and Blood Institute (1R01HL152219).
