Role of Synaptic Inhibition in the Coupling of the Respiratory Rhythms that Underlie Eupnea and Sigh Behaviors

The preBötzinger complex (preBötC) gives rise to two types of breathing behavior under normal physiological conditions: eupnea and sighing. Here, we examine the neural mechanisms that couple their underlying rhythms. We measured breathing in awake intact adult mice and recorded inspiratory rhythms from the preBötC in neonatal mouse brainstem slice preparations. We show previously undocumented variability in the temporal relationship between sigh breaths or bursts and their preceding eupneic breaths or inspiratory bursts. Investigating the synaptic mechanisms for this variability in vitro, we further show that pharmacological blockade of chloride-mediated synaptic inhibition strengthens inspiratory-to-sigh temporal coupling. These findings contrast with previous literature, which suggested glycinergic inhibition linked sigh bursts to their preceding inspiratory bursts with minimal time intervals. Furthermore, we verify that pharmacological disinhibition did not alter the duration of the prolonged interval that follows a sigh burst before resumption of the inspiratory rhythm. These results demonstrate that synaptic inhibition does not enhance coupling between sighs and preceding inspiratory events or contribute to post-sigh apneas. Instead, we conclude that excitatory synaptic mechanisms coordinate inspiratory (eupnea) and sigh rhythms.