Large scale neural dynamics that govern normal and disrupted breathing

Breathing is a vital sensorimotor behavior maintained throughout life that must be concurrently robust and flexible. Despite the relative simplicity of this behavior, the neural circuits that drive and maintain breathing are distributed throughout a large population of anatomically distributed and molecularly diverse neural population that compose the rostro-caudally extended Ventral Respiratory Column (VRC) The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here we introduce an experimental preparation that allows for large-scale electrophysiological recordings along the rostrocaudal extent of the medulla We combine recordings from Neuropixel probes with optogenetic tagging and 3D histological reconstructions to detail the respiratory-related activities of VRC populations in intact, freely breathing mice.
We apply dimensionality reduction techniques to the activity of simultaneously recorded VRC populations to show that dynamics of these populations evolve along a continuous, rotational, low-dimensional trajectory that is consistent across animals and recordings. Inspiratory and expiratory activity can be well described as an alternation between disjoint, but intersecting, linear dynamical systems governed by unstable fixed points. Notably, the offset of inspiration forms an attractive target in neural population space, expanding the classical idea of the “inspiratory off-switch” to the population dynamics of the entire VRC.
We further test how these rotational dynamics are disrupted by systemic perturbations to respiratory dynamics: opioids and hypoxia. We show that opioids cause myriad diverse changes in single unit spiking activity across the VRC. However, the underlying low-dimensional structure is preserved, but evolution through low-dimensional trajectories is slowed, suggesting that there are redundant network solutions to preserve respiratory function in response to such perturbations. In contrast, during hypoxia induced gasping, the rotational dynamics observed during normal breathing (eupnea) collapse to form ballistic all-or-nothing efforts.