Role of synaptic inhibition in the coupling of the respiratory rhythms that underlie eupnea and sigh behaviors

Borrus, Daniel S; Smith, Gregory D.; Negro, Christopher A. Del

doi:10.1101/721829

Cited by 3 publications

References 32 publications

(23 reference statements)

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Breathing Behaviors in Common Marmoset (Callithrix jacchus)

Bishop

Turk

Adeck

et al. 2020

Preprint

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The respiratory system maintains homeostatic levels of oxygen (O2) and carbon dioxide (CO2) in the body through rapid and efficient regulation of frequency and dept (tidal volume) of breathing. The use of common marmoset (Callithrix jacchus), a New World non-human primate (NHP) model, in neuroscience is increasing, however, the data on their breathing is limited and their respiratory behaviors have yet to be characterized. Using Whole-body Plethysmography in room air as well as in hypoxic (low O2) and hypercapnic (high CO2) conditions, we sought to define breathing behaviors in an awake, freely behaving marmosets. Additionally, we instituted and optimized an analysis toolkit for unsupervised analysis of the respiratory activities in common marmoset. Our findings indicate that marmoset’s exposure to hypoxia decreased metabolic rate and increased sigh rate. However, the hypoxic condition did not augment the ventilatory response as reported in other animals. Hypercapnia, on the other hand, increased both the frequency and tidal volume as expected. In this study, we shed light on the breathing behaviors of common marmosets in a variety of O2 and CO2 conditions to further understand the breathing behaviors in NHPs.

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Breathing Behaviors in Common Marmoset (Callithrix jacchus)

Bishop

Turk

Adeck

et al. 2020

Preprint

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Sigh breathing rhythm depends on intracellular calcium oscillations in a population of inspiratory rhythmogenic preBötzinger complex neurons in mice

Borrus

Grover

Smith

et al. 2022

Preprint

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The preBötzinger Complex (preBötC) of the lower brainstem generates two breathing-related rhythms: one for inspiration on a timescale of seconds and another that produces larger amplitude sighs on the order of minutes. Their underlying mechanisms and cellular origins remain incompletely understood. We resolve these problems via a joint experiment and modeling approach. Blocking purinergic gliotransmission does not perturb either rhythm and imaging experiments show that both rhythms emanate from the same glutamatergic neuron population. We hypothesized that these two disparate rhythms emerge in tandem wherein recurrent excitation gives rise to inspiratory rhythm while a calcium oscillator generates sighs; there is no obligatory role for gliotransmission, hyperpolarization activated mixed cationic current (Ih) in neurons, or synaptic inhibition-mediated coupling of separate populations. We developed a mathematical model that instantiates our working hypothesis. Tests of model predictions validate the single-population rhythmogenic framework, reproducing disparate breathing-related frequencies and the ability for inspiratory and sigh rhythms to be separately regulated in support of respiration under a wide array of conditions. Here we show how a single neuron population exploits two cellular tool-kits: one involving voltage-dependent membrane properties and synaptic excitation for inspiratory breathing (eupnea) and an intracellular biochemical oscillator for sighs, which ventilate and maintain optimal function in the compliant mammalian lung.

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Evaluating the Burstlet Theory of Inspiratory Rhythm and Pattern Generation

Kallurkar¹,

Grover²,

Picardo³

et al. 2019

eNeuro

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The preBötzinger complex (preBötC) generates the rhythm and rudimentary motor pattern for inspiratory breathing movements. Here, we test "burstlet" theory (Kam et al., 2013a), which posits that low amplitude burstlets, subthreshold from the standpoint of inspiratory bursts, reflect the fundamental oscillator of the preBötC. In turn, a discrete suprathreshold process transforms burstlets into full amplitude inspiratory bursts that drive motor output, measurable via hypoglossal nerve (XII) discharge in vitro. We recap observations by Kam and Feldman in neonatal mouse slice preparations: field recordings from preBötC demonstrate bursts and concurrent XII motor output intermingled with lower amplitude burstlets that do not produce XII motor output. Manipulations of excitability affect the relative prevalence of bursts and burstlets and modulate their frequency. Whole-cell and photonic recordings of preBötC neurons suggest that burstlets involve inconstant subsets of rhythmogenic interneurons. We conclude that discrete rhythm-and pattern-generating mechanisms coexist in the preBötC and that burstlets reflect its fundamental rhythmogenic nature.

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Role of synaptic inhibition in the coupling of the respiratory rhythms that underlie eupnea and sigh behaviors

Cited by 3 publications

References 32 publications

Breathing Behaviors in Common Marmoset (Callithrix jacchus)

Breathing Behaviors in Common Marmoset (Callithrix jacchus)

Sigh breathing rhythm depends on intracellular calcium oscillations in a population of inspiratory rhythmogenic preBötzinger complex neurons in mice

Evaluating the Burstlet Theory of Inspiratory Rhythm and Pattern Generation

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