Muscarinic Inhibition of Hypoglossal Motoneurons: Possible Implications for Upper Airway Muscle Hypotonia during REM Sleep DOI Creative Commons
Lin Zhu,

Nancy L. Chamberlin,

Elda Arrigoni

и другие.

Journal of Neuroscience, Год журнала: 2019, Номер 39(40), С. 7910 - 7919

Опубликована: Авг. 16, 2019

Proper function of pharyngeal dilator muscles, including the genioglossus muscle tongue, is required to maintain upper airway patency. During sleep, activity these muscles suppressed, and as a result individuals with obstructive sleep apnea experience repeated episodes closure when they are asleep, in particular during rapid-eye-movement (REM) sleep. Blocking cholinergic transmission hypoglossal motor nucleus (MoXII) restores REM activity, highlighting importance inhibition neurons (HMNs) Glutamatergic afferent input from parahypoglossal (PH) region HMNs critical for MoXII respiratory output. We hypothesized that state-dependent regulation may be mediated by this pathway. Here we studied effects adult male female mice using patch-clamp recordings brain slices. Using channelrhodopsin-2-assisted circuit mapping, first demonstrated PH glutamatergic directly robustly activate (PH Glut → HMNs). then show carbachol consistently depresses effect presynaptic. Additionally, affects variable combination muscarinic-mediated excitatory inhibitory responses. Altogether, our results suggest signaling impairs suppressing premotoneurons inhibiting HMNs. Our findings highlight complexity control at both presynaptic postsynaptic levels provide possible mechanism suppression activity. SIGNIFICANCE STATEMENT Individuals can breathe adequately awake but Similar skeletal postural responsible maintaining an open become hypotonic Unlike spinal motoneurons controlling inhibited glycinergic monoaminergic disfacilitation inhibition. In study, how inhibits through muscarinic receptors. potential hypotonia

Язык: Английский

Hypothesis: Pulmonary Afferent Activity Patterns During Slow, Deep Breathing Contribute to the Neural Induction of Physiological Relaxation DOI Creative Commons
Donald J. Noble, Shawn Hochman

Frontiers in Physiology, Год журнала: 2019, Номер 10

Опубликована: Сен. 13, 2019

Control of respiration provides a powerful voluntary portal to entrain and modulate central autonomic networks. Slowing deepening breathing as relaxation technique has shown promise in variety cardiorespiratory stress-related disorders, but few studies have investigated the physiological mechanisms conferring its benefits. Recent evidence suggests that at frequency near 0.1 Hz (6 breaths per minute) promotes behavioral baroreflex resonance effects maximize heart rate variability. Breathing around this appears elicit resonant coherent features neuro-mechanical interactions optimize function. Here we explore neurophysiology slow, deep propose coincident respiratory baroreceptor afferent activity cycling An important role is assigned preferential recruitment slowly-adapting pulmonary afferents (SARs) during prolonged inhalations project discrete areas brainstem within nucleus solitary tract (NTS) initiate inhibitory actions on downstream targets. Conversely, exhalations terminate SAR activate arterial baroreceptors via increases blood pressure stimulate, through NTS projections, parasympathetic outflow heart. Reciprocal afferent-evoked combine enhance sympathetic inhalation exhalation, respectively. This leads pronounced variability phase with cycle (respiratory sinus arrhythmia) improved ventilation-perfusion matching. relay neurons extensively network encode pattern may anxiety, arousal, attention. In our model, rhythms also support expression slow cortical induce functional state alert relaxation, and, nasal respiration-based olfactory signaling, recruit hippocampal pathways boost memory consolidation. Collectively, assert neurophysiological processes recruited cognitive therapeutic outcomes obtained various mind-body practices. Future are required better understand physio-behavioral involved, including animal models control for confounding factors such expectancy biases.

Язык: Английский

Процитировано

119

PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate DOI Creative Commons
Clément Menuet, Angela A. Connelly, Jaspreet K. Bassi

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Июнь 15, 2020

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, neurons entraining the activity pre-sympathetic parasympathetic cardiovascular neurons. Using a combination optogenetic inhibition excitation vivo situ rats, as well neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form kernel for inspiratory rhythm generation, directly modulate Specifically, inhibitory preBötC cardiac neuron whilst excitatory sympathetic vasomotor activity, generating heart respiration. Our data reveal yet more functions entrained to preBötC, role cardiorespiratory oscillations. The findings have implications pathologies, such hypertension failure, where entrainment diminished exaggerated.

Язык: Английский

Процитировано

72

The multifunctionality of the brainstem breathing control circuit DOI Creative Commons
Kevin Yackle, Jeehaeh Do

Current Opinion in Neurobiology, Год журнала: 2025, Номер 90, С. 102974 - 102974

Опубликована: Янв. 28, 2025

Subconscious breathing is generated by a network of brainstem nodes with varying purposes, like pacing or patterning certain breath phase. Decades anatomy, pharmacology, and physiology studies have identified characterized the system's fundamental properties that produce robust breathing, we now well-conceived computational models are based on detailed descriptions neuronal connectivity, biophysical properties, functions in breathing. In total, considerable understanding control circuit. But, last five years, utilization molecular genetic approaches to study neural subtypes within each node has led new era circuit research explains how integrated more complex behaviors speaking running connected other physiological systems our state-of-mind. This review will describe basic role key components then highlight transformative discoveries broaden these brain areas. These serve illustrate creativity exciting future research.

Язык: Английский

Процитировано

1

Defining the Rhythmogenic Elements of Mammalian Breathing DOI Open Access
Jan‐Marino Ramirez, Nathan A. Baertsch

Physiology, Год журнала: 2018, Номер 33(5), С. 302 - 316

Опубликована: Авг. 15, 2018

Breathing's remarkable ability to adapt changes in metabolic, environmental, and behavioral demands stems from a complex integration of its rhythm-generating network within the wider nervous system. Yet, this complicates identification specific rhythmogenic elements. Based on principles learned smaller rhythmic networks invertebrates, we define criteria that identify elements mammalian breathing discuss how they interact produce robust, dynamic breathing.

Язык: Английский

Процитировано

75

Optogenetic stimulation of pre–Bötzinger complex reveals novel circuit interactions in swallowing–breathing coordination DOI Creative Commons
Alyssa Huff, Marlusa Karlen‐Amarante, Teresa Pitts

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(29)

Опубликована: Июль 14, 2022

The coordination of swallowing with breathing, in particular inspiration, is essential for homeostasis most organisms. While much has been learned about the neuronal network critical inspiration mammals, pre-Bötzinger complex (preBötC), little known how this interacts swallowing. Here we activate within preBötC excitatory neurons (defined as

Язык: Английский

Процитировано

35

Role of the postinspiratory complex in regulating swallow–breathing coordination and other laryngeal behaviors DOI Creative Commons
Alyssa Huff, Marlusa Karlen‐Amarante, Luíz M. Oliveira

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Июнь 5, 2023

Breathing needs to be tightly coordinated with upper airway behaviors, such as swallowing. Discoordination leads aspiration pneumonia, the leading cause of death in neurodegenerative disease. Here, we study role postinspiratory complex (PiCo) coordinating breathing and Using optogenetic approaches freely anesthetized ChATcre:Ai32, Vglut2cre:Ai32 intersectional recombination ChATcre:Vglut2FlpO:ChR2 mice reveals PiCo mediates protective behaviors. Activation during inspiration or beginning postinspiration triggers swallow behavior an all-or-nothing manner, while there is a higher probability for stimulating only laryngeal activation when activated further into expiration. Laryngeal dependent on stimulation duration. Sufficient bilateral necessary preserving physiological motor sequence since few neurons unilateral blurred behavioral responses. We believe acts interface between pattern generator preBötzinger coordinate breathing. Investigating PiCo’s coordination will aid understanding discoordination neurological diseases.

Язык: Английский

Процитировано

23

Parabrachial tachykinin1-expressing neurons involved in state-dependent breathing control DOI Creative Commons

Joseph W. Arthurs,

Anna J. Bowen, Richard D. Palmiter

и другие.

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

Опубликована: Фев. 21, 2023

Abstract Breathing is regulated automatically by neural circuits in the medulla to maintain homeostasis, but breathing also modified behavior and emotion. Mice have rapid patterns that are unique awake state distinct from those driven automatic reflexes. Activation of medullary neurons control does not reproduce these patterns. By manipulating transcriptionally defined parabrachial nucleus, we identify a subset express Tac1 , Calca gene exerts potent precise conditional awake, anesthetized, via projections ventral intermediate reticular zone medulla. Activating drives frequencies match physiological maximum through mechanisms differ underlie breathing. We postulate this circuit important for integration with state-dependent behaviors emotions.

Язык: Английский

Процитировано

22

Inspiratory and sigh breathing rhythms depend on distinct cellular signalling mechanisms in the preBötzinger complex DOI Creative Commons
Daniel S. Borrus,

Marco K. Stettler,

Cameron J. Grover

и другие.

The Journal of Physiology, Год журнала: 2024, Номер 602(5), С. 809 - 834

Опубликована: Фев. 14, 2024

Abstract Breathing behaviour involves the generation of normal breaths (eupnoea) on a timescale seconds and sigh order minutes. Both rhythms emerge in tandem from single brainstem site, but whether how cell population can generate two disparate remains unclear. We posit that recurrent synaptic excitation concert with depression cellular refractoriness gives rise to eupnoea rhythm, whereas an intracellular calcium oscillation is slower by orders magnitude rhythm. A mathematical model capturing these dynamics simultaneously generates frequencies, which be separately regulated physiological parameters. experimentally validated key predictions regarding signalling. All vertebrate brains feature network oscillator drives breathing pump for regular respiration. However, air‐breathing mammals compliant lungs susceptible collapse, rhythmogenic may have refashioned ubiquitous signalling systems produce second rhythm (for sighs) prevents atelectasis without impeding eupnoea. image Key points simplified activity‐based preBötC inspiratory neuron population. Inspiration attributable canonical excitatory mechanism. Sigh emerges The predicts perturbations uptake release across endoplasmic reticulum counterintuitively accelerate decelerate rhythmicity, respectively, was validated. Vertebrate evolution adapted existing mechanisms slow oscillations needed optimize pulmonary function mammals.

Язык: Английский

Процитировано

8

Trpm4 ion channels in pre-Bötzinger complex interneurons are essential for breathing motor pattern but not rhythm DOI Creative Commons
Maria Cristina D. Picardo, Yae K. Sugimura, Kaitlyn E. Dorst

и другие.

PLoS Biology, Год журнала: 2019, Номер 17(2), С. e2006094 - e2006094

Опубликована: Фев. 21, 2019

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized be rhythmogenic, reducing ICAN is predicted slow down or stop breathing; its contributions motor pattern would reflected in the magnitude of (output). We tested role(s) using reverse genetic techniques diminish putative ion channels Trpm4 Trpc3 preBötC neurons vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased tidal volume breaths yet surprisingly increased frequency, often followed by gasping and fatal respiratory failure. Mice Trpc3-targeted shRNA survived no changes breathing. Patch-clamp field recordings from mouse slices also showed an increase frequency a decrease bursts presence antagonist 9-phenanthrol, whereas pyrazole-3 (pyr-3) inconsistent effects effect frequency. These data suggest mediates ICAN, whose influence contradicts direct role rhythm generation. conclude Trpm4-mediated indispensable for output but not rhythmogenic core mechanism central generator.

Язык: Английский

Процитировано

44

Respiratory disorders of Parkinson’s disease DOI
Yasmin C. Aquino, Laís M. Cabral, Nicole C. Miranda

и другие.

Journal of Neurophysiology, Год журнала: 2021, Номер 127(1), С. 1 - 15

Опубликована: Ноя. 24, 2021

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in substantia nigra, mainly affecting people over 60 yr age. Patients develop both classic symptoms (tremors, muscle rigidity, bradykinesia, and postural instability) nonclassical (orthostatic hypotension, neuropsychiatric deficiency, sleep disturbances, respiratory disorders). Thus, patients with PD can have a significantly impaired quality life, especially when they do not multimodality therapeutic follow-up. The alterations associated this syndrome are main cause mortality PD. They be classified as peripheral caused disorders upper airways or muscles involved breathing central triggered functional deficits important located brainstem control. Currently, there little research describing these disorders, therefore, no well-established knowledge about subject, making treatment difficult. In review, history pathology data changes obtained thus far will addressed.

Язык: Английский

Процитировано

39