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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Neuromedin B-Expressing Neurons in the Retrotrapezoid Nucleus Regulate Respiratory Homeostasis and Promote Stable Breathing in Adult Mice

Journal of Neuroscience, Год журнала: 2023, Номер 43(30), С. 5501 - 5520

Опубликована: Июнь 8, 2023

Respiratory chemoreceptor activity encoding arterial P co 2 and o is a critical determinant of ventilation. Currently, the relative importance several putative mechanisms for maintaining eupneic breathing respiratory homeostasis debated. Transcriptomic anatomic evidence suggests that bombesin-related peptide Neuromedin-B ( Nmb ) expression identifies neurons in retrotrapezoid nucleus (RTN) mediate hypercapnic ventilatory response, but functional support missing. In this study, we generated transgenic -Cre mouse used Cre-dependent cell ablation optogenetics to test hypothesis RTN are necessary CO -dependent drive breathe adult male female mice. Selective ∼95% causes compensated acidosis because alveolar hypoventilation, as well profound instability respiratory-related sleep disruption. Following lesion, mice were hypoxemic at rest prone severe apneas during hyperoxia, suggesting oxygen-sensitive mechanisms, presumably peripheral chemoreceptors, compensate loss neurons. Interestingly, ventilation following -lesion was unresponsive hypercapnia, behavioral responses (freezing avoidance) hypoxia response preserved. Neuroanatomical mapping shows highly collateralized innervate centers pons medulla with strong ipsilateral preference. Together, dedicated effects /pH maintain intact conditions suggest malfunction these could underlie etiology certain forms sleep-disordered humans. SIGNIFICANCE STATEMENT chemoreceptors stimulate neural motor output regulate , thereby optimal gas exchange. Neurons express proposed be important process, has not been established. Here, developed model demonstrated fundamental stimulatory on breathing. Our data indicate -expressing an integral component This work highlights interdependent dynamic integration - O -sensing mammals.

Язык: Английский

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Adrenergic C1 neurons monitor arterial blood pressure and determine the sympathetic response to hemorrhage

Cell Reports, Год журнала: 2022, Номер 38(10), С. 110480 - 110480

Опубликована: Март 1, 2022

Hemorrhage initially triggers a rise in sympathetic nerve activity (SNA) that maintains blood pressure (BP); however, SNA is suppressed following severe loss causing hypotension. We hypothesized adrenergic C1 neurons the rostral ventrolateral medulla (C1RVLM) drive increase during compensated hemorrhage, and reduction C1RVLM contributes to hypotension decompensated hemorrhage. Using fiber photometry, we demonstrate increases hemorrhage falls at onset of optogenetics combined with direct recordings SNA, show activation mediates BP stability whereas suppression associated cardiovascular collapse Notably, re-activating restores normal levels. In conclusion, are nodal point for response loss.

Язык: Английский

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Central respiratory chemoreception

Handbook of clinical neurology, Год журнала: 2022, Номер unknown, С. 37 - 72

Опубликована: Янв. 1, 2022

Язык: Английский

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Upregulation of breathing rate during running exercise by central locomotor circuits in mice

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Май 22, 2023

Abstract While respiratory adaptation to exercise is compulsory cope with the increased metabolic demand, neural signals at stake remain poorly identified. Using circuit tracing and activity interference strategies in mice, we uncover here two systems by which central locomotor network can enable augmentation relation running activity. One originates mesencephalic region (MLR), a conserved controller. Through direct projections onto neurons of preBötzinger complex that generate inspiratory rhythm, MLR trigger moderate increase frequency, prior to, or even absence of, locomotion. The other lumbar enlargement spinal cord containing hindlimb motor circuits. When activated, through retrotrapezoid nucleus (RTN), it also potently upregulates breathing rate. On top identifying critical underpinnings for hyperpnea, these data expand functional implication cell types pathways are typically regarded as “locomotor” “respiratory” related.

Язык: Английский

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Rostral ventrolateral medulla, retropontine region and autonomic regulations

Autonomic Neuroscience, Год журнала: 2021, Номер 237, С. 102922 - 102922

Опубликована: Ноя. 19, 2021

Язык: Английский

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Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

eLife, Год журнала: 2022, Номер 11

Опубликована: Янв. 4, 2022

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics WAG/Rij rat, an established rodent model of epilepsy, we demonstrate are highly sensitive arterial carbon dioxide, suggesting pH. Moreover, consistently activated neurons within intralaminar nuclei thalamus, a structure implicated seizure generation. We show thalamus also contains pH-sensitive neurons. Collectively, these observations suggest activates provoke seizures.

Язык: Английский

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Respiratory rhythm and pattern generation: Brainstem cellular and circuit mechanisms

Handbook of clinical neurology, Год журнала: 2022, Номер unknown, С. 1 - 35

Опубликована: Янв. 1, 2022

Язык: Английский

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Criteria for central respiratory chemoreceptors: experimental evidence supporting current candidate cell groups

Frontiers in Physiology, Год журнала: 2023, Номер 14

Опубликована: Сен. 1, 2023

An interoceptive homeostatic system monitors levels of CO 2 /H + and provides a proportionate drive to respiratory control networks that adjust lung ventilation maintain physiologically appropriate rapidly regulate tissue acid-base balance. It has long been suspected the sensory cells responsible for major CNS contribution this so-called chemoreception are located in brainstem—but there is still substantial debate field as which specific subserve function. Indeed, at present time, several cell types have championed potential chemoreceptors, including neurons astrocytes. In review, we advance set criteria necessary sufficient definitive acceptance any type chemoreceptor. We examine extant evidence supporting consideration different putative chemoreceptor candidate context these also note each where not yet fulfilled. By enumerating hope provide useful heuristic can be employed both evaluate various existing candidates, focus effort on experimental tests satisfy remaining requirements acceptance.

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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