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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Activation of the periaqueductal gray controls respiratory output through a distributed brain network

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Introduction The periaqueductal gray (PAG) has been previously established to play a key role in producing the vital changes respiration occurring response threat. However, it is not fully understood how PAG activation alters ongoing respiratory output, nor which pathways mediate these effects, as several regions have identified influence activity. Methods We used optogenetic tools conjunction with EMG recordings of inspiratory and expiratory musculature determine on short (250 ms) longer (10–15 s) timescales muscle Through cFOS mapping, we also downstream brain were likely modulated by including preBötzinger Complex (preBötC) lateral parafacial area (pFL). then stimulated terminals those whether their activity can account for observed effects stimulation. Results Directly stimulating resulted prominent all recorded activities reset breathing rhythm either phase-independent or phase-dependent manner. In contrast, preBötC pFL long shorter timescale stimuli could completely replicate direct stimulation did produce any reset. Conclusions Our results show that are mediated solely inputs more involve integration across larger network brainstem areas.

Language: Английский

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Spatio-temporal segregation between sensory relay and swallowing pre-motor population activities by optical imaging in the rat nucleus of the solitary tract

Pflügers Archiv - European Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

The nucleus tractus solitarius (NTS) contains neurons that relay sensory swallowing commands information from the oropharyngeal cavity and premotor of dorsal group (DSG). However, spatio-temporal dynamics interplay between DSG is not well understood. Here, we employed fluorescence imaging after microinjection calcium indicator into NTS in an arterially perfused brainstem preparation rat (n = 8) to investigate neuronal population activity response superior laryngeal nerve (SLN) stimulation. Respiratory motor activities were determined by simultaneous recordings phrenic vagal (PNA, VNA). analysis SLN stimulation near threshold triggering a allowed us analyze Ca2+ signals related DSG. We show activation triggers spatially confined exclusively unilateral stimulated at short latencies (114.3 ± 94.4 ms). SLN-evoked triggered bilaterally longer (200 145.2 ms) engaged anatomically distributed across medulla oblongata. originating preceded evoked VNA swallow bursts, thus drive pools are located outside In conclusion, study illuminates spatial–temporal features sensory-motor integration further supports hypothesis harbors pre-motor may generate activity, while first-order

Language: Английский

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The Potential Role of Oxidative Stress in Modulating Airway Defensive Reflexes

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 568 - 568

Published: May 9, 2025

Airway defensive reflexes, such as pharyngeal swallowing, coughing, and sneezing, play a pivotal role in maintaining airway homeostasis. These reflexes are controlled by complex mechanisms primarily governed specific neuronal circuitry the brainstem, referred to central pattern generators. behaviors also require optimal conditions for peripheral organs within alimentary tracts, including nose, pharynx, larynx, trachea, which vital ensuring appropriate responsiveness motor outputs. Oxidative stress is linked development progress of impaired functions those behaviors. Dysphagia caused or impairments, neurodegeneration related networks laryngeal desensitization, likely associated with an increased level oxidative stress. Chronic inflammation allergic sensitization lower airways, asthma, elevate levels diminish activity antioxidant defense enzymes, exacerbate severity respiratory conditions. Antioxidant supplements offer promising therapeutic benefits facilitating recovery distorted although limited information has been provided concerning strategies. Further studies necessary enhance our understanding pathophysiology dysphagia diseases stress, well develop new treatment strategies these disorders.

Language: Английский

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Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: May 6, 2024

The sympathetic nervous system modulates arterial blood pressure. Individuals with obstructive sleep apnea (OSA) experience numerous nightly hypoxic episodes and exhibit elevated activity to the cardiovascular leading hypertension. This suggests that OSA disrupts normal respiratory-sympathetic coupling. study investigates role of postinspiratory complex (PiCo) preBötzinger (preBötC) in coupling under control conditions following exposure chronic intermittent hypoxia (CIH) for 21 days (5% O

Language: Английский

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Role of the Kölliker-Fuse/Parabrachial Complex in generation of post-inspiratory vagal and sympathetic nerve activities

Journal of Neurophysiology, Journal Year: 2024, Volume and Issue: 132(5), P. 1496 - 1506

Published: Oct. 2, 2024

Inhibition of neurons in the pontine Kölliker–Fuse/parabrachial complex (KF-PBN) differentially inhibited postinspiratory (post-I) activity vagal and sympathetic outputs. The strong recruitment post-I that occurs response to hypoxemia is selectively abolished by KF-PBN inhibition. This suggests 1) outputs may be generated partially independent mechanisms 2) are a preeminent source drive for generation eupneic activity.

Language: Английский

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Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

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

Published: Nov. 9, 2023

Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurological and systemic comorbidities, including dysphagia, or disordered swallow, discoordination with breathing. However, the mechanism which chronic hypoxia (CIH) causes dysphagia unknown. Recently, we showed postinspiratory complex (PiCo) acts as an interface between swallow pattern generator (SPG) inspiratory rhythm generator, preBötzinger complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo characterized by interneurons co-expressing transporters for glutamate (Vglut2) acetylcholine (ChAT). Here show optogenetic stimulation ChATcre:Ai32, Vglut2cre:Ai32, ChATcre:Vglut2FlpO:ChR2 mice exposed CIH does not alter coordination, but unexpectedly disrupts behavior via triggering variable motor patterns. This suggests glutamatergic-cholinergic neurons are only critical regulation also play important role modulation patterning. Our study disruption, seen OSA, involves central nervous mechanisms interfering patterning laryngeal activation. These findings crucial understanding underlying both other disorders.

Language: Английский

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Interdependence of cellular and network properties in respiratory rhythmogenesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

ABSTRACT How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and persistent sodium current ( I NaP ) lies at heart of this debate. Although widely expressed, pacemaker hypothesis considers it essential because endows a small subset neurons with intrinsic bursting or “pacemaker” activity. In contrast, burstlet theory dispensable rhythm emerges from “pre-inspiratory” spiking activity driven feed-forward network interactions. Using computational modeling, we discover that changes in spike shape can dissociate bursting. Consistent many experimental benchmarks, conditional effects on during simulated oxygenation, development, extracellular potassium, temperature alter prevalence pre-inspiratory without altering role . Our results support unifying where excitatory interactions, but not spiking, are critical interdependent features preBötC rhythmogenesis. SIGNIFICANCE STATEMENT Breathing vital rhythmic process originating complex. Since its discovery 1991, there has been spirited debate about whether respiratory generation as property specialized capabilities, endowed currents. Here, using propose data-driven model which bridges gap these competing theories. model, both cellular properties (a current) (recurrent excitation), bursting, generation.

Language: Английский

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The breath shape controls intonation of mouse vocalizations

Published: Jan. 18, 2024

Intonation in speech is the control of vocal pitch to layer expressive meaning communication, like increasing indicate a question. Also, stereotyped patterns are used create distinct “words”, ten sounds murine lexicon. A basic tone created by exhalation through constricted laryngeal voice box, and it thought that more complex utterances produced solely dynamic changes tension. But perhaps, shifting also results from altering power exhalation. Consistent with latter model, we describe intonation many adult vocalizations follows deviations brainstem vocalization central pattern generator, iRO, can this breath pattern. Consequently, ectopic activation iRO not only induces phonation, but compose most These reveal novel mechanism for intonation.

Language: Английский

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Apnea behavior in early- and late-stage mouse models of Parkinson's disease: Cineradiographic analysis of spontaneous breathing, acute stress, and swallowing

Respiratory Physiology & Neurobiology, Journal Year: 2024, Volume and Issue: 323, P. 104239 - 104239

Published: Feb. 22, 2024

Language: Английский

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