Role of synaptic inhibition in the coupling of the respiratory rhythms that underlie eupnea and sigh behaviors

Abstract

The preBotzinger Complex (preBotC) gives rise to two types of breathing behavior: eupnea and sighing. Here, we examine the neural mechanisms that couple their underlying rhythms by recording from the preBotC in neonatal mouse brainstem slice preparations. It has been proposed that chloride-mediated synaptic inhibition couples inspiratory (eupnea-related) bursts and sigh bursts, but we find no evidence to support that notion. First, we characterize a fluctuating temporal relationship between sigh bursts and their preceding inspiratory bursts; their coupling is far weaker than previously described. Surprisingly, selective blockade of inhibitory synapses strengthened (rather than weakened) that phasic inspiratory-sigh burst relationship. Furthermore, pharmacological disinhibition did not alter the duration of the prolonged interval that follows a sigh burst prior to resumption of the inspiratory rhythm. These results demonstrate that coupling between inspiratory and sigh rhythms does not depend on synaptic inhibition.\n\nSIGNIFICANCE STATEMENTBreathing consists of eupnea and sigh breaths, which differ in their magnitude and frequency. Both breath types emerge from a brainstem microcircuit that coordinates their timing. Here, we advance understanding of these rhythms by assessing the nature and strength of their coordination, and by showing that synaptic inhibition does not enforce their temporal coupling in contrast to conventional understanding. This study provides insights into the basic neural mechanisms that link oscillations of different amplitude and frequency in a core oscillator.