Department of Physiology, Women and Children Research Institute & Centre for Neuroscience, University of Alberta, 3020F Katz Group Centre, Edmonton, AB, Canada
Breathing is an essential behavior for mammalian life that is controlled by neuronal networks located in the brainstem. The brainstem region of the paraFacial Respiratory Group (pFRG) has been proposed to be critical for expiratory rhythm generation. The major expiratory muscles in mammals are the abdominal (ABD) muscles that, if active during expiration, force air out of the lungs below its resting level (i.e., active expiration), facilitate the subsequent inspiration and thereby promote ventilation.
We previously demonstrated that active recruitment of expiratory muscle activity occurs during periods of REM in natural sleep and in REM-like states under urethane anesthesia (Pagliardini et al., 2012, J. Neurosci. 32(33) 11259-70; Pagliardini et al., 2013 PlosONE 8(7):e70411)
In this study, we tested the hypothesis that cholinergic transmission, which is potentiated in periods of REM sleep, is involved in the generation of expiratory activity in urethane anesthetized rats.
Adult rats were anesthetized with urethane (1.5mg/kg), vagotomised, and EMG electrodes were implanted in the diaphragm, genioglossus and ABD muscles. Tracheotomy was performed to measure inspiratory and expiratory airflow.
Local application into the pFRG of the acetylcholinesterase enzyme inhibitor Physostigmine (5mM,200nl), which locally increases endogenous acetylcholine levels potentiated ABDEMG activity as well as tidal volume.
Local application into the pFRG of the muscarinic agonist carbachol (1mM), induced potent recruitment of ABDEMG activity, expiratory flow and consequent increase in tidal volume. This effect was completely inhibited by pre-application of the muscarinic antagonist scopolamine (1mM) and reversed by a 2hr washout.
These results demonstrate that cholinergic muscarinic transmission contribute to excitation of pFRG neurons and promotes active recruitment of ABDEMG activity and active expiratory flow.
Research funded by NSERC (SP); RB was funded by an NSERC summer studentship