An inspiration-off attractor supports the robust and flexible control of breathing.

Breathing is a fundamental motor rhythm necessary to sustain life. The rhythm and pattern of breathing arises from the coordination of a rostrocaudally extended ventral respiratory column (VRC) in the medulla. Although recurrent excitation is sufficient for rhythmic bursting in reduced in vitro preparations, comparatively less is understood about how inhibition and excitation interact with feedback circuits to generate the breathing rhythm in vivo. Here, we expand on the classical "inspiratory-off switch" model that inhibitory signaling from lung stretch afferent pathways plays a critical role in generating the breathing rhythm in vivo. We perform high-density extracellular recordings along the length of the VRC during optogenetic and physiological manipulations and apply computational analyses to characterize how these perturbations govern low-dimensional neural dynamics. We show that stimulation of GABAergic afferents of the nucleus of the solitary tract advance or delay breathing in a manner similar to, but quantitatively distinct from, inhibition local to the VRC. We use generative dynamical models to show that inhibitory activity controls respiratory activity through transient stabilization of an attractive region of the low-dimensional manifold corresponding to expiration. Together, these results propose an "inspiratory-off attractor" model that underlies network level control of breathing in vivo.