Breathing Rhythm and Pattern and Their Influence on Emotion

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 223 - 247

Published: March 9, 2022

Breathing is a vital rhythmic motor behavior with surprisingly broad influence on the brain and body. The apparent simplicity of breathing belies complex neural control system, central pattern generator (bCPG), that exhibits diverse operational modes to regulate gas exchange coordinate an array behaviors. In this review, we focus selected advances in our understanding bCPG. At core bCPG preBötzinger (preBötC), which drives inspiratory rhythm via unexpectedly sophisticated emergent mechanism. Synchronization dynamics underlying preBötC rhythmogenesis imbue system robustness lability. These are modulated by inputs from throughout generate rhythmic, patterned activity widely distributed. connectivity emerging literature support link between breathing, emotion, cognition becoming experimentally tractable. bring great potential for elucidating function dysfunction other mammalian circuits.

Language: Английский

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Emergent Elements of Inspiratory Rhythmogenesis: Network Synchronization and Synchrony Propagation

Neuron, Journal Year: 2020, Volume and Issue: 106(3), P. 482 - 497.e4

Published: March 3, 2020

Language: Английский

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Neuronal mechanisms underlying opioid-induced respiratory depression: our current understanding

Journal of Neurophysiology, Journal Year: 2021, Volume and Issue: 125(5), P. 1899 - 1919

Published: April 7, 2021

Opioid-induced respiratory depression (OIRD) represents the primary cause of death associated with therapeutic and recreational opioid use. Within United States, rate from abuse since early 1990s has grown disproportionally, prompting classification as a nationwide “epidemic.” Since this time, we have begun to unravel many fundamental cellular systems-level mechanisms opioid-related death. However, factors such individual vulnerability, neuromodulatory compensation, redundancy effects across central peripheral nervous systems created barrier concise, integrative view OIRD. review, bring together multiple perspectives in field OIRD create an overarching viewpoint what know, where essential topic research going forward into future.

Language: Английский

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Understanding and countering opioid‐induced respiratory depression

British Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 180(7), P. 813 - 828

Published: June 5, 2021

Respiratory depression is the proximal cause of death in opioid overdose, yet mechanisms underlying this potentially fatal outcome are not well understood. The goal review to provide a comprehensive understanding pharmacological opioid‐induced respiratory depression, which could lead improved therapeutic options counter as other detrimental effects opioids on breathing. development tolerance system also discussed, differences degree caused by various agonists. Finally, potential future agents aimed at reversing or avoiding through non‐opioid receptor targets and certain advantages over naloxone. By providing an overview network, will benefit research countering depression. LINKED ARTICLES This article part themed issue Advances Opioid Pharmacology Time Epidemic. To view articles section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc

Language: Английский

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Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Aug. 17, 2021

The analgesic utility of opioid-based drugs is limited by the life-threatening risk respiratory depression. Opioid-induced depression (OIRD), mediated μ-opioid receptor (MOR), characterized a pronounced decrease in frequency and regularity inspiratory rhythm, which originates from medullary preBötzinger Complex (preBötC). To unravel cellular- network-level consequences MOR activation preBötC, MOR-expressing neurons were optogenetically identified manipulated transgenic mice vitro vivo. Based on these results, model OIRD was developed silico. We conclude that hyperpolarization - expressing preBötC alone does not phenocopy OIRD. Instead, effects are twofold: (1) pre-inspiratory spiking reduced (2) excitatory synaptic transmission suppressed, thereby disrupting network-driven rhythmogenesis. These dual mechanisms opioid action act synergistically to make normally robust rhythm-generating network particularly prone collapse when challenged with exogenous opioids.

Language: Английский

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Opioid suppression of an excitatory pontomedullary respiratory circuit by convergent mechanisms

eLife, Journal Year: 2023, Volume and Issue: 12

Published: June 14, 2023

Opioids depress breathing by inhibition of interconnected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population neurons dorsolateral pons, particularly Kölliker-Fuse (KF) nucleus, that are key mediators opioid-induced depression. However, projection target synaptic connections MOR-expressing KF unknown. Here, we used retrograde labeling brain slice electrophysiology to determine project ventrolateral medulla, including preBötzinger complex (preBötC) rostral ventral group (rVRG). These medullary-projecting, pontine express FoxP2 distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, release glutamate onto excitatory preBötC rVRG via monosynaptic projections, which is inhibited presynaptic receptors. Surprisingly, majority receiving MOR-sensitive glutamatergic input themselves hyperpolarized opioids, suggesting selective opioid-sensitive circuit inhibit this pontomedullary three mechanisms-somatodendritic MORs on medullary neuron terminals medulla-all could contribute

Language: Английский

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Anatomical distribution of µ-opioid receptors, neurokinin-1 receptors, and vesicular glutamate transporter 2 in the mouse brainstem respiratory network

Journal of Neurophysiology, Journal Year: 2024, Volume and Issue: 132(1), P. 108 - 129

Published: May 15, 2024

Opioid drugs can cause serious respiratory side-effects by binding to µ-opioid receptors (MORs) in brainstem regions that control breathing. To better understand the and their cellular subpopulations may be vulnerable modulation opioids, we provide a comprehensive map of Oprm1 (gene encoding MORs) mRNA expression throughout modulate Notably, identify glutamatergic neurokinin-1 receptor-expressing cells as potentially opioid worthy further investigation using targeted approaches.

Language: Английский

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Interdependence of cellular and network properties in respiratory rhythm generation

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(19)

Published: May 1, 2024

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (I

Language: Английский

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The role of acetazolamide in sleep apnea at sea level: a systematic review and meta-analysis

Journal of Clinical Sleep Medicine, Journal Year: 2021, Volume and Issue: 17(6), P. 1295 - 1304

Published: Feb. 4, 2021

The recognition of specific endotypes as drivers sleep apnea suggests the need therapies targeting individual mechanisms. Acetazolamide is known to stabilize respiration at high altitude but benefits sea level are less well understood.All controlled studies acetazolamide in obstructive and/or central (CSA) were evaluated. primary outcome was apnea-hypopnea index.Fifteen trials with a total 256 patients pooled our systematic review. reduced overall index (mean difference [MD] -15.82, 95% CI: -21.91 -9.74, P < .00001) (MD -22.60, -29.11 -16.09, .00001), not -10.29, -33.34 12.77, = .38). respiratory related arousal -0.82, -1.56 -0.08, .03), improved partial arterial oxygen 11.62, 9.13-14.11, mean saturation 1.78, 0.53-3.04, .005), time 25.74, 4.10-47.38, .02), N2 3.34, 0.12-6.56, .04) and efficiency 4.83, 0.53-9.13, .03).Acetazolamide improves several metrics apnea. drug may be clinical benefit loop gain various etiologies patterns. existence heterogeneity an important limitation applicability analysis.Registry: PROSPERO; Name: effect level: review meta analysis; URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020163316; Identifier: CRD42020163316.

Language: Английский

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Putting the theory into ‘burstlet theory’ with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex

eLife, Journal Year: 2022, Volume and Issue: 11

Published: April 5, 2022

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In vitro slice preparations containing preBötC, extracellular potassium must be elevated above physiological levels (to 7–9 mM) to observe regular rhythmic respiratory motor output hypoglossal nerve which preBötC projects. Reexamination of how K + affects has revealed that low-amplitude oscillations persist at levels. These oscillatory events are subthreshold standpoint transmission and dubbed burstlets. Burstlets neural rhythmogenic subpopulation within some instances may fail recruit larger network events, or bursts, required generate output. The fraction (burstlet fraction) decreases sigmoidally with increasing potassium. observations underlie burstlet theory rhythm generation. Experimental computational studies have suggested recruitment non-rhythmogenic component population requires intracellular Ca 2+ dynamics activation calcium-activated nonselective cationic current. this study, we show calcium driven by synaptically triggered influx well release/uptake endoplasmic reticulum conjunction current can reproduce offer an explanation for many key properties associated Altogether, our modeling work provides mechanistic basis unify wide range experimental findings on generation preBötC.

Language: Английский

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