The psychophysiology of the sigh: I: The sigh from the physiological perspective

Severs, Liza J.; Vlemincx, Elke; Ramirez, Jan‐Marino

doi:10.1016/j.biopsycho.2022.108313

Cited by 13 publications

(13 citation statements)

References 124 publications

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“…We conclude that glia and gliotransmission are not mandatory for sigh rhythmogenesis because attenuating purinergic signalling, the dominant means by which astrocytes interact with preBötC neurons (Huxtable et al, 2010;Okada et al, 2012;Rajani et al, 2016), did not preclude or modify sigh rhythmogenesis. In another experimental context, blocking P2Y 1 receptors stopped the sigh rhythm consistently in vitro, but it did not stop sigh breathing in more than half of the adult mice directly injected with a high (500 μM) dose of MRS2279 in the preBötC (Severs et al, 2023). Our conclusion is not incompatible -purinergic gliotransmission does not appear to be necessary for sigh behaviour -but our data in vitro are incongruous.…”

Section: Discussioncontrasting

confidence: 53%

“…Therefore, it is conceivable that astrocytes generate sigh rhythm and communicate it to preBötC neurons via purinergic P2 receptors. Specifically P2Y 1 receptors may be important for sigh rhythmogenesis in vitro (Severs et al, 2023).…”

Section: Inspiratory and Sigh Rhythms Can Be Separately Modulatedmentioning

confidence: 99%

“…The sigh mechanism involves intracellular calcium (Ca 2+ ) signalling. First, drugs that target voltage-gated Ca 2+ channels and intracellular Ca 2+ release, as well as Ca 2+ chelators perturb sighs (Lieske & Ramirez, 2006a;Lieske et al, 2000;Morgado-Valle et al, 2022;Severs et al, 2023;Toporikova et al, 2015). Further, the sigh rhythm can be accelerated by group I metabotropic glutamate receptors, M3 acetylcholine receptors and bombesin-like peptide receptors, all of which act via G q/11 and phospholipase C to produce inositol 1,4,5-trisphosphate-mediated intracellular Ca 2+ release (Li et al, 2016;Lieske & Ramirez, 2006b;Ramos-Álvarez et al, 2015;Tryba et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…First, the literature does not support dichotomous eupnoea-and sigh-specialized neuron populations in the preBötC; rather, the consensus is that rhythmogenic neurons belong to the same, or extensively overlapping, preBötC network(s) (Lieske & Ramirez, 2006a, b;Lieske et al, 2000;Tryba et al, 2008;Viemari et al, 2013). However, if there are discrete eupnoea-and sigh-dedicated cell populations, then one population may be non-neural, consisting instead of astrocytes (Severs et al, 2023). Second, an inspiratory rhythmogenic role for I NaP is still a matter of considerable debate, with a branch of genetic knockout, and knockdown perturbations (da Silva et al, 2023) and pharmacological experiments (Del Negro, Morgado-Valle, et al, 2002;Del Negro et al, 2005;Pace et al, 2007a;Peña et al, 2004) unsupportive, and a parallel branch of modelling, pharmacology, and optogenetic experiments supportive (Ausborn et al, 2018;Koizumi & Smith, 2008;Phillips & Rubin, 2019;Yamanishi et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex

Borrus,

Stettler,

Grover

et al. 2024

The Journal of Physiology

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Breathing behaviour involves the generation of normal breaths (eupnoea) on a timescale of seconds and sigh breaths on the order of minutes. Both rhythms emerge in tandem from a single brainstem site, but whether and how a single cell population can generate two disparate rhythms remains unclear. We posit that recurrent synaptic excitation in concert with synaptic depression and cellular refractoriness gives rise to the eupnoea rhythm, whereas an intracellular calcium oscillation that is slower by orders of magnitude gives rise to the sigh rhythm. A mathematical model capturing these dynamics simultaneously generates eupnoea and sigh rhythms with disparate frequencies, which can be separately regulated by physiological parameters. We experimentally validated key model predictions regarding intracellular calcium signalling. All vertebrate brains feature a network oscillator that drives the breathing pump for regular respiration. However, in air‐breathing mammals with compliant lungs susceptible to collapse, the breathing rhythmogenic network may have refashioned ubiquitous intracellular signalling systems to produce a second slower rhythm (for sighs) that prevents atelectasis without impeding eupnoea. imageKey points A simplified activity‐based model of the preBötC generates inspiratory and sigh rhythms from a single neuron population. Inspiration is attributable to a canonical excitatory network oscillator mechanism. Sigh emerges from intracellular calcium signalling. The model predicts that perturbations of calcium uptake and release across the endoplasmic reticulum counterintuitively accelerate and decelerate sigh rhythmicity, respectively, which was experimentally validated. Vertebrate evolution may have adapted existing intracellular signalling mechanisms to produce slow oscillations needed to optimize pulmonary function in mammals.

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Section: Discussioncontrasting

confidence: 53%

Section: Inspiratory and Sigh Rhythms Can Be Separately Modulatedmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex

Borrus,

Stettler,

Grover

et al. 2024

The Journal of Physiology

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“…Another unique aspect of fentanyl's impact on respiratory function was its complete inhibition of sigh activity – an integral airway defence mechanism. Sighs, characterized as an augmented breath followed by a brief apnoea, serve crucial roles in maintaining lung function, preventing atelectasis and promoting gas exchange (Cammarota et al., 2011; Hess & Bigatello, 2002; Li & Yackle, 2017; Ramirez, 2014; Ramirez et al., 2022; Severs et al., 2022). In contrast to fentanyl, morphine only slightly reduced sigh activity.…”

Section: Discussionmentioning

confidence: 99%

A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability

Burgraff,

Baertsch,

Ramirez

2023

The Journal of Physiology

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This study provides an in‐depth analysis of the distinct consequences of the opioid drugs morphine and fentanyl during opioid‐induced respiratory depression (OIRD). We explored the physiological implications of both drugs on ventilation and airway patency in anaesthetized mice. Our results revealed a similar reduction in respiratory frequency with equivalent scaled dosages of fentanyl and morphine, though the onset of suppression was more rapid with fentanyl. Additionally, fentanyl resulted in transient airflow obstructions during the inspiratory cycle, which were absent following morphine administration. Notably, these fentanyl‐specific obstructions were eliminated with tracheostomy, implicating the upper airways as a major factor contributing to fentanyl‐induced respiratory depression. We further demonstrate that bronchodilators salbutamol and adrenaline effectively reversed these obstructions, highlighting the bronchi's contribution to fentanyl‐induced airflow obstruction. Our study also uncovered a significant reduction in sighs during OIRD, which were eliminated by fentanyl and markedly reduced by morphine. Finally, we found that fentanyl‐exposed mice had reduced survival under hypoxic conditions compared to mice given morphine, demonstrating that fentanyl becomes more lethal in the context of hypoxaemia. Our findings shed light on the distinct and profound impacts of these opioids on respiration and airway stability and lay the foundation for improved opioid use guidelines and more effective OIRD prevention strategies. imageKey points Both morphine and fentanyl significantly suppressed respiratory frequency, but the onset of suppression was faster with fentanyl. Also, while both drugs increased tidal volume, this effect was more pronounced with fentanyl. Fentanyl administration resulted in transient obstructions during the inspiratory phase, suggesting its unique impact on airway stability. This obstruction was not observed with morphine. The fentanyl‐induced obstructions were reversed by administering bronchodilators such as salbutamol and adrenaline. This suggests a possible therapeutic strategy for mitigating the adverse airway effects of fentanyl. Both drugs reduced the frequency of physiological sighs, a key mechanism to prevent alveolar collapse. However, fentanyl administration led to a complete cessation of sighs, while morphine only reduced their occurrence. Fentanyl‐treated mice showed a significantly reduced ability to survive under hypoxic conditions compared to those administered morphine. This indicates that the impacts of hypoxaemia during opioid‐induced respiratory depression can vary based on the opioid used.

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Stable Character Recognition Strategy Using Ventilation Manipulation in ERP-Based Brain-Computer Interface

Park,

Ju,

Won

2023

Lecture Notes in Computer Science

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The psychophysiology of the sigh: I: The sigh from the physiological perspective

Cited by 13 publications

References 124 publications

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex

A comparative examination of morphine and fentanyl: unravelling the differential impacts on breathing and airway stability

Stable Character Recognition Strategy Using Ventilation Manipulation in ERP-Based Brain-Computer Interface

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