Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

Abstract

23The rhythm generating network for breathing must continuously adjust to 24 changing metabolic and behavioral demands. Here, we examine network-based 25 mechanisms in the mouse preBӧtzinger complex using substance P, a potent excitatory 26 modulator of breathing frequency and stability, as a tool to dissect network properties 27 that underlie dynamic breathing. We find that substance P does not alter the balance of 28 excitation and inhibition during breaths or the duration of the resulting refractory period. 29Instead, mechanisms of recurrent excitation between breaths are enhanced such that 30the rate that excitation percolates through the network is increased. Based on our 31 results, we propose a conceptual framework in which three distinct phases, the 32 inspiratory phase, refractory phase, and percolation phase, can be differentially 33 modulated to influence breathing dynamics and stability. Unravelling mechanisms that 34 support this dynamic control may improve our understanding of nervous system 35 disorders that destabilize breathing, many of which are associated with changes in 36 brainstem neuromodulatory systems.

Microglia shape the embryonic development of mammalian respiratory networks

“…In a number of preparations, we also assessed the sensitivity of the preBötC network to Substance P (SP), a well-known and potent modulatory peptide of this respiratory oscillator’s operation (Gray et al, 1999; Baertsch and Ramirez, 2019). Exposure to 0.5 µM SP (as commonly used on such reduced embryonic preparations; (Thoby-Brisson et al, 2005; Chevalier et al, 2016)) induced a significant increase ( P < 0.001) in the preBötC’s rhythm frequency in both genotypes to 10, 2 ± 0.6 bursts/min in WT preparations (n=4), and to 9,6 ± 0.6 bursts/min in Pu.1 -/- preparations (n = 4), (Fig.…”

Brain, Breathing and the Heart

“…1D). Critical for the generation of these rhythms are glutamatergic neurons that become active during the pre-inspiratory phase and are characterized by a peak discharge pattern during inspiration 37 . These excitatory inspiratory neurons are characterized by the transcription factor Dbx1.…”