Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling

BMC Biology, Год журнала: 2023, Номер 21(1)

Опубликована: Апрель 15, 2023

Abstract Breathing is a singularly robust behavior, yet this motor pattern continuously modulated at slow and fast timescales to maintain blood-gas homeostasis, while intercalating orofacial behaviors. This functional multiplexing goes beyond the rhythmogenic function that typically ascribed medullary respiration-modulated networks may explain lack of progress in identifying mechanism constituents respiratory rhythm generator. By recording optically along ventral column medulla, we found convergent evidence distributed over dispersed heterogeneous network synchronized by electrotonic coupling across neuronal syncytium. First, high-speed recordings revealed inspiratory onset occurred synchronously did not emanate from core. Second, following synaptic isolation, stationary rhythmic activity was detected column. attenuated gap junction blockade silenced tetrodotoxin. The layering syncytial complicates identification mechanism, enabling multiplexing.

Язык: Английский

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Interdependence of cellular and network properties in respiratory rhythmogenesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 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.

Язык: Английский

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Modeling effects of variable preBötzinger Complex network topology and cellular properties on opioid-induced respiratory depression and recovery

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 31, 2023

Abstract The pre-Bötzinger complex (preBotC), located in the medulla, is essential rhythm-generating neural network for breathing. actions of opioids on this impair its ability to generate robust, rhythmic output, contributing life-threatening opioid-induced respiratory depression (OIRD). occurrence OIRD varies across individuals and internal external states, increasing risk opioid use, yet mechanisms variability are largely unknown. In study, we utilize a computational model preBötC perform several silico experiments exploring how differences topology intrinsic properties neurons influence sensitivity rhythm opioids. We find that rhythms produced by networks exhibit variable responses simulated opioids, similar vitro . This primarily due random can be manipulated imposed changes connectivity neuronal properties. Our results identify features may regulate susceptibility Significance Statement brainstem generates breathing disrupted drugs. However, response surprisingly unpredictable. By constructing models network, illustrate distribution biophysical patterns within individual predict their show modulation these make more susceptible or resistant effects

Язык: Английский

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How neural networks walk and chew gum

The Journal of Physiology, Год журнала: 2024, Номер 602(5), С. 767 - 768

Опубликована: Фев. 10, 2024

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by authors. Any queries (other than missing content) should be directed to corresponding author article.

Язык: Английский

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The hypoxic respiratory response of the pre-Bötzinger complex

Heliyon, Год журнала: 2024, Номер 10(14), С. e34491 - e34491

Опубликована: Июль 1, 2024

Язык: Английский

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Modeling Effects of Variable preBötzinger Complex Network Topology and Cellular Properties on Opioid-Induced Respiratory Depression and Recovery

eNeuro, Год журнала: 2024, Номер 11(3), С. ENEURO.0284 - 23.2023

Опубликована: Янв. 22, 2024

The preBötzinger complex (preBötC), located in the medulla, is essential rhythm-generating neural network for breathing. actions of opioids on this impair its ability to generate robust, rhythmic output, contributing life-threatening opioid-induced respiratory depression (OIRD). occurrence OIRD varies across individuals and internal external states, increasing risk opioid use, yet mechanisms variability are largely unknown. In study, we utilize a computational model preBötC perform several silico experiments exploring how differences topology intrinsic properties neurons influence sensitivity rhythm opioids. We find that rhythms produced by networks exhibit variable responses simulated opioids, similar vitro. This primarily due random can be manipulated imposed changes connectivity neuronal properties. Our results identify features may regulate susceptibility

Язык: Английский

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Exploring the role of the Kölliker–Fuse nucleus in breathing variability by mathematical modelling

The Journal of Physiology, Год журнала: 2023, Номер 602(1), С. 93 - 112

Опубликована: Дек. 8, 2023

Abstract The Kölliker–Fuse nucleus (KF), which is part of the parabrachial complex, participates in generation eupnoea under resting conditions and control active abdominal expiration when increased ventilation required. Moreover, dysfunctions KF neuronal activity are believed to play a role emergence respiratory abnormalities seen Rett syndrome (RTT), progressive neurodevelopmental disorder associated with an irregular breathing pattern frequent apnoeas. Relatively little known, however, about intrinsic dynamics neurons within how their synaptic connections affect contribute irregularities. In this study, we use reduced computational model consider several dynamical regimes paired different input sources determine combinations compatible known experimental observations. We further build on these findings identify possible interactions between other components neural circuitry. Specifically, present two models that both simulate eupnoeic as well RTT‐like phenotypes. Using nullcline analysis, types inhibitory inputs leading patterns suggest local circuit organizations. When identified properties present, also exhibit quantal acceleration late‐expiratory activity, hallmark featuring forced exhalation, increasing inhibition KF, reported experimentally. Hence, instantiate plausible hypotheses forms network interactions, thus providing general framework specific predictions for future testing. image Key points involved regulating normal controlling during ventilation. Dysfunction thought (RTT). This study utilizes modelling explore compatibility By analysing configurations, identifies lead proposes potential Two presented patterns. These provide testable investigations, offering understanding interactions.

Язык: Английский

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The role of Kölliker-Fuse nucleus in breathing variability

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 15, 2023

Abstract The Kölliker-Fuse nucleus (KF), which is part of the parabrachial complex, participates in generation eupnea under resting conditions and control active abdominal expiration when increased ventilation required. Moreover, dysfunctions KF neuronal activity are believed to play a role emergence respiratory abnormalities seen Rett syndrome (RTT), progressive neurodevelopmental disorder associated with an irregular breathing pattern frequent apneas. Relatively little known, however, about intrinsic dynamics neurons within how their synaptic connections affect contribute irregularities. In this study, we use reduced computational model consider several dynamical regimes paired different input sources determine combinations compatible known experimental observations. We further build on these findings identify possible interactions between other components neural circuitry. Specifically, present two models that both simulate eupneic as well RTT-like phenotypes. Using nullcline analysis, types inhibitory inputs leading patterns suggest local circuit organizations. When identified properties present, also exhibit quantal acceleration late-expiratory activity, hallmark featuring forced exhalation, increasing inhibition KF, reported experimentally. Hence, instantiate plausible hypotheses forms network interactions, thus providing general framework specific predictions for future testing. Key points involved regulating normal controlling during ventilation. Dysfunction thought (RTT). This study utilizes modeling explore compatibility By analyzing configurations, identifies lead proposes potential Two presented patterns. These provide investigations, offering understanding interactions.

Язык: Английский

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