Attractor dynamics that govern breathing are differentially perturbed by inhibitory and excitatory populations of the Ventral Respiratory Column

Distributed and diverse populations of neurons throughout the Ventral Respiratory Column (VRC) are involved in the generation and maintenance of breathing. We have recently shown that the network-wide dynamics of these populations evolve through rotational trajectories in a low-dimensional latent neural space. These rotations evolve continuously through both inspiration and expiration, and they target a low-dimensional inspiratory-off attractor. It remains unknown how these rotational dynamics respond to perturbations of specific subsets of VRC populations. Here we record from the rostrocaudal extent of the VRC using high-density Neuropixel probes in-vivo in anesthetized mice while optogenetically stimulating subsets of neurons by Cre-driven expression of channel rhodopsin. These stimulations cause both widespread activation and deactivation of recorded populations. We find that brainstem wide stimulation of inhibitory neurons perturbs low-dimensional population trajectories towards the inspiration-off attractor, regardless of trajectory location at the time of stimulation. After cessation of stimulation, all trajectories proceed inexorably toward the inspiration-off point, and the cycle resets. When inhibitory populations are stimulated during the expiratory period, the population dynamics are clamped close to the inspiration-off attractor. Stimulation of glutamatergic populations, in contrast, directs the trajectories to a different region near the center of the rotation. However, upon cessation of excitatory stimulation, the trajectories immediately relax to the closest point along the rotational manifold, and the cycle resumes. Stimulation of either GABA-ergic or glutamatergic populations perturbs the dynamics perpendicular to the ongoing rotations; however stimulation of either Dbx1+ or cholinergic populations perturbs the populations along the current heading of the trajectories. Together, these data highlight a critical role of inhibition in the procession of VRC population dynamics, and suggest that the inspiration-off attractor is targeted by inhibitory mechanisms. R01 HL151389; R01 HL126523; R01 HL144801; F32HL159904 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.