Key result
In mice, respiratory neural population activity evolves along continuous rotational trajectories that are slowed but preserved during opioid-induced respiratory depression, whereas severe hypoxia causes these dynamics to collapse into all-or-none ballistic efforts.
Why the study?
Technical challenges have limited the simultaneous interrogation of the entire ventral respiratory column neural population, despite the well-known rhythmic properties of its individual nuclei.
Latent neural population dynamics reveal that the ventral respiratory column operates via robust rotational trajectories during normal breathing and opioid depression, which collapse into ballistic efforts during hypoxic gasping.
Distinguishes opioid-resilient from hypoxia-vulnerable respiratory dynamics in mice; leaves open translation to human respiratory failure therapies.
Breathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostrocaudally 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 15,000 medullary units using high-density electrophysiology, opto-tagging and histological reconstruction. Population dynamics analysis reveals consistent rotational trajectories through a low-dimensional neural manifold. These rotations are robust and maintained even during opioid-induced respiratory depression. During severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts. Thus, latent dynamics provide a unifying lens onto the activities of large, heterogeneous populations of neurons involved in the simple, yet vital, behavior of breathing, and well describe how these populations respond to a variety of perturbations.
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Bush et al. (2024) studied Opioid-induced respiratory depression and gasping (animal model) (n=36). Morphine and Hypoxia vs. Baseline (normal breathing) was evaluated on Neural population dynamics (rotational trajectories in low-dimensional neural manifold). In mice, respiratory neural population activity evolves along continuous rotational trajectories that are slowed but preserved during opioid-induced respiratory depression, whereas severe hypoxia causes these dynamics to collapse into all-or-none ballistic efforts.
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