The integrated brain network that controls respiration

eLife, Год журнала: 2023, Номер 12

Опубликована: Март 8, 2023

Respiration is a brain function on which our lives essentially depend. Control of respiration ensures that the frequency and depth breathing adapt continuously to metabolic needs. In addition, respiratory control network has organize muscular synergies integrate ventilation with posture body movement. Finally, coupled cardiovascular emotion. Here, we argue can handle this all by integrating brainstem central pattern generator circuit in larger also comprises cerebellum. Although currently not generally recognized as center, cerebellum well known for its coordinating modulating role motor behavior, autonomic nervous system. review, discuss regions involved respiration, their anatomical functional interactions. We how sensory feedback result adaptation these mechanisms be compromised various neurological psychological disorders. demonstrate generators are part integrated regions.

Язык: Английский

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Hypoxia sensing in the body: An update on the peripheral and central mechanisms

Experimental Physiology, Год журнала: 2023, Номер 109(4), С. 461 - 469

Опубликована: Ноя. 30, 2023

Abstract An adequate supply of O 2 is essential for the maintenance cellular activity. Systemic or local hypoxia can be experienced during decreased availability associated with diseases, a combination both. Exposure to triggers adjustments in multiple physiological systems body generate appropriate homeostatic responses. However, significant reductions arterial partial pressure , life‐threatening and cause maladaptive changes cell damage death. To mitigate impact limited on activity, chemoreceptors rapidly detect respond triggering orchestrated responses increased ventilation cardiac output, blood flow redistribution metabolic adjustments. In mammals, peripheral carotid are considered main hypoxic sensors primary source excitatory feedback driving respiratory, cardiovascular autonomic current evidence indicates that CNS contains specialized brainstem spinal cord regions also sense stimulate brain networks independently inputs. this manuscript, we review discoveries about functioning their contribution monitoring levels parenchyma mounting cardiorespiratory maintain homeostasis. We discuss implications chemoreflex‐related mechanisms paediatric adult pathologies.

Язык: 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, Год журнала: 2024, Номер 132(1), С. 108 - 129

Опубликована: Май 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.

Язык: Английский

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On The Biophysical Complexity of Brain Dynamics: An Outlook

Dynamics, Год журнала: 2022, Номер 2(2), С. 114 - 148

Опубликована: Май 5, 2022

The human brain is a complex network whose ensemble time evolution directed by the cumulative interactions of its cellular components, such as neurons and glia cells. Coupled through chemical neurotransmission receptor activation, these individuals interact with one another to varying degrees triggering variety activity from internal biological reconfigurations external other agents. Consequently, local dynamic connections mediating magnitude direction influence cells have on are highly nonlinear facilitate, respectively, potentially chaotic multicellular higher-order collaborations. Thus, statistical physical system, culmination produces global emergent behaviors, enabling dynamical, adaptive, efficient response macroscopic network. Microstate typically facilitated synaptic structural plasticity mechanisms that alter degree coupling (magnitude influence) upon each other, dictating type coordinated macrostate emergence in populations neural These can emerge form regions synchronized clusters about center frequency composed individual cell collaborations fundamental collective organization. A single mode synchronization insufficient for computational needs brain. components (cellular multiple synchronous populations, nuclei, even regions), different patterns behavior produce an spatiotemporal spectral bandwidth corresponding dynamical state Furthermore, hierarchical self-similar structures support properties operate effectively efficiently. Neuroscience has come long way since inception; however, comprehensive intuitive understanding how works still amiss. It becoming evident any singular perspective grandiose biophysical complexity within inadequate. purpose this paper provide outlook multitude perspectives, including constraints nature. Upon assessing prior research efforts, paper, we identify path future effort should pursue inspire progress neuroscience.

Язык: Английский

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Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment

Acta Physiologica, Год журнала: 2024, Номер 240(4)

Опубликована: Янв. 23, 2024

Abstract Aim The central CO 2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. retrotrapezoid nucleus crucial hub for chemosensitivity; its ablation or inhibition attenuates chemoreflexes diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying impairment in these disorders. Progesterone stimulates breathing chemoreflexes. However, mechanisms sites actions remain unknown the experimental use synthetic progestins patients animal models have been met with mixed outcomes. Methods We investigated whether acute chronic administration progestinic drug, etonogestrel, could rescue following selective lesion saporin toxin. Adult female Sprague Dawley rats were grouped based on size determined by number surviving chemosensitive neurons, ventilatory responses measured whole body plethysmography. Results Ventilatory hypercapnia (but not hypoxia) compromised lesion‐dependent manner. Chronic etonogestrel treatment improved chemosensitivity selectively moderate lesion, that residual neurons are required etonogestrel‐induced recovery. Conclusion This study provides new evidence as stimulants under testable model assessing mechanism action network.

Язык: Английский

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Intrinsic and synaptic mechanisms controlling the expiratory activity of excitatory lateral parafacial neurones of rats

The Journal of Physiology, Год журнала: 2021, Номер 599(21), С. 4925 - 4948

Опубликована: Сен. 12, 2021

Abstract Active expiration is essential for increasing pulmonary ventilation during high chemical drive (hypercapnia). The lateral parafacial (pF L ) region, which contains expiratory neurones, drives abdominal muscles active in response to hypercapnia. However, the electrophysiological properties and synaptic mechanisms determining activity of pF as well specific conditions their emergence, are not fully understood. Using whole cell electrophysiology single quantitative RT‐PCR techniques, we describe intrinsic properties, phenotype respiratory‐related inputs expression under hypercapnia‐induced expiration, using situ preparations juvenile rats. We also evaluated whether these neurones possess CO 2 /[H + ] sensitivity burst generating properties. GABAergic glycinergic inhibition inspiration suppressed glutamatergic normocapnia. In hypercapnia, escape generate discharges at end expiration. Evidence contribution post‐inhibitory rebound, Ca V 3.2 isoform T‐type 2+ channels intracellular [Ca presented. Neither bursting mediated by persistent Na current, nor or sensitive ion channels/receptors (TASK GPR4) were observed. On other hand, hyperpolarisation‐activated cyclic nucleotide–gated twik‐related K leak recorded. Post‐synaptic disinhibition play important roles generation oscillations region hypercapnia image Key points Hypercapnia induces rats recruitment a population region. both suppress inspiratory phases reduces leading neurones; evidence voltage‐gated neither burster sensors, do express receptors.

Язык: Английский

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

Frontiers in Physiology, Год журнала: 2025, Номер 16

Опубликована: Янв. 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.

Язык: Английский

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Cholinergic projections to the preBötzinger complex

The Journal of Comparative Neurology, Год журнала: 2023, Номер 531(13), С. 1317 - 1332

Опубликована: Май 21, 2023

Abstract Rhythmic inspiratory activity is generated in the preBötzinger complex (preBötC), a neuronal network located bilaterally ventrolateral medulla. Cholinergic neurotransmission affects respiratory rhythmogenic neurons and inhibitory glycinergic preBötC. Acetylcholine has been extensively investigated given that cholinergic fibers receptors are present functional preBötC, important sleep/wake cycling, modulate frequency through its action on preBötC neurons. Despite role modulating rhythm, source of acetylcholine input to not known. In study, we used retrograde anterograde viral tracing approaches transgenic mice expressing Cre‐recombinase driven by choline acetyltransferase promoter identify inputs Surprisingly, observed very few, if any, projections originating from laterodorsal pedunculopontine tegmental nuclei (LDT/PPT), two main cholinergic, state‐dependent systems long hypothesized as On contrary, identified glutamatergic GABAergic/glycinergic PPT/LDT send Although these contribute minimally direct modulation neurons, they could be involved regulation breathing. Our data also suggest appears originate neighboring regions medulla, intermediate reticular formation, lateral paragigantocellularis, nucleus solitary tract.

Язык: Английский

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Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats

eLife, Год журнала: 2024, Номер 13

Опубликована: Фев. 14, 2024

PHOX2B is a transcription factor essential for the development of different classes neurons in central and peripheral nervous system. Heterozygous mutations coding region are responsible occurrence Congenital Central Hypoventilation Syndrome (CCHS), rare neurological disorder characterised by inadequate chemosensitivity life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects caused part improper or function expressing retrotrapezoid nucleus (RTN), hub CO 2 chemosensitivity. Although rodents during well established, its role adult respiratory network remains unknown. In this study, we investigated whether reduction expression chemosensitive neuromedin-B (NMB) RTN altered function. Four weeks following local injection lentiviral vector short hairpin RNA (shRNA) targeting Phox2b mRNA, was observed Nmb compared to both naive rats injected with non-target shRNA. knockdown did not affect breathing room air under hypoxia, but ventilation significantly impaired hypercapnia. alter it associated reduced Task2 Gpr4 , two /pH sensors RTN. We conclude brain has an important chemoreception CCHS beyond developmental period may contribute

Язык: Английский

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Etonogestrel Administration Reduces the Expression of PHOX2B and Its Target Genes in the Solitary Tract Nucleus

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4816 - 4816

Опубликована: Апрель 27, 2022

Heterozygous mutations of the transcription factor PHOX2B are responsible for Congenital Central Hypoventilation Syndrome, a neurological disorder characterized by inadequate respiratory response to hypercapnia and life-threatening hypoventilation during sleep. Although no cure is currently available, it was suggested that potent progestin drug provides partial recovery chemoreflex response. Previous in vitro data show direct molecular link between progestins expression. However, mechanism through which these drugs ameliorate breathing vivo remains unknown. Here, we investigated effects chronic administration Etonogestrel (ETO) on function transcriptional activity adult female rats. We assessed with whole-body plethysmography measured genomic changes brain regions important control. Our results ETO reduced metabolic activity, leading an enhanced concurrent increased cycle variability at rest. Furthermore, ETO-treated brains showed mRNA protein expression its target genes selectively dorsal vagal complex, while other areas were unaffected. Histological analysis suggests occurred solitary tract nucleus (NTS). Thus, propose NTS, rich both progesterone receptors PHOX2B, good candidate ETO-induced modulation.

Язык: Английский

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