Latent neural population dynamics underlying normal breathing, opioid induced respiratory depression, and gasping

Abstract

Breathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostro-caudally aligned set of medullary nuclei called the 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 characterize over 13,000 VRC units using high-density electrophysiology, opto-tagging, and histological reconstruction. Population dynamics analysis reveals interactions between inspiratory and expiratory dynamical states give rise to a low-dimensional, elliptical neural manifold. The structure of this manifold is robust and maintained even during opioid-induced respiratory depression (OIRD). However, during severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts.