Key result
Ventral Respiratory Column neural population dynamics exhibit a robust low-dimensional manifold that is maintained during opioid-induced respiratory depression but collapses into ballistic efforts during severe hypoxia-induced gasping.
Why the study?
Technical challenges have limited simultaneous interrogation of the entire Ventral Respiratory Column population to understand how its neural dynamics generate rhythmic breathing.
VRC neural population dynamics exhibit a robust low-dimensional elliptical manifold that is maintained during opioid-induced respiratory depression but collapses into ballistic trajectories during severe hypoxia-induced gasping.
Distinguishes neural dynamics in opioid vs hypoxic respiratory failure; leaves open human translation.
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.
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Bush et al. (2022) studied Normal breathing, opioid-induced respiratory depression, and gasping (n=30). Morphine and Hypoxia vs. Baseline (eupnea in 100% O2) was evaluated on Neural population dynamics (low-dimensional manifold structure). Ventral Respiratory Column neural population dynamics exhibit a robust low-dimensional manifold that is maintained during opioid-induced respiratory depression but collapses into ballistic efforts during severe hypoxia-induced gasping.
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