Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An airway protection program revealed by sweeping genetic control of vagal afferents

ABSTRACT: Sensory neurons evoke a suite of defensive reflexes to ensure airway integrity. Dysfunction of laryngeal neurons is life-threatening, causing pulmonary aspiration, dysphagia, and choking, yet relevant sensory pathways remain poorly understood. Here, we discover rare throat-innervating neurons (~100 neurons/mouse) that guard the airways against assault. We used genetic tools that broadly cover a vagal/glossopharyngeal sensory neuron atlas to map, ablate, and control specific afferent populations. Optogenetic activation of vagal P2RY1 neurons evokes a coordinated airway defense program- apnea, vocal fold adduction, swallowing, and expiratory reflexes. Selective ablation of vagal P2RY1 neurons eliminates protective responses to laryngeal water and acid challenge. Anatomical mapping revealed numerous terminal morphologies in the larynx, with P2RY1 neurons forming corpuscular endings that appose laryngeal taste buds. Epithelial cells are primary airway sentinels that communicate with second-order P2RY1 neurons through ATP. These findings provide mechanistic insights into airway defense, and a general molecular/genetic roadmap for internal organ sensation by the vagus nerve.

ORGANISM(S): Mus musculus

PROVIDER: GSE145216 | GEO | 2020/04/05

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A vagal reflex evoked by airway closure

Project description:Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and on a moment-by-moment basis, enact vital reflexes to maintain respiratory function. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax, or airway compression. Here, we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses, and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, while ablating NEBs or vagal PVALB neurons eliminated gasping to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of PIEZO2 in NEBs also eliminated responses to airway closure. NEBs are dispensable for the Hering-Breuer inspiratory reflex, indicating that discrete terminal structures detect airway closure and inflation. Like Merkel cells involved in touch sensation, NEBs are PIEZO2-expressing epithelial cells, and moreover, are critical for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways, and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

2024-03-06 | GSE252735 | GEO

Neuroendocrine cells initiate protective upper airway reflexes

Project description:Airway neuroendocrine (NE) cells have been proposed to serve as specialized sensory epithelial cells that modulate respiratory behavior by communicating with nearby nerve endings. However, their functional properties and physiological roles in the healthy lung, trachea and larynx remain largely unknown. Here, we show that NE cells in these compartments possess distinct biophysical properties, but share sensitivity to the commonly aspirated noxious stimuli, water and acid. Moreover, we found that tracheal and laryngeal NE cells protect the airways by releasing ATP to activate purinoreceptive sensory neurons that initiate swallowing and expiratory reflexes. Our work uncovers striking molecular and biophysical diversity of NE cells across the airways and reveals mechanisms by which these specialized excitable cells serve as sentinels for activating a critical nociceptive circuit.

2024-04-26 | GSE256180 | GEO

The impact of influenza pulmonary infection and inflammation on vagal bronchopulmonary sensory neurons

Project description:Influenza A virus (IAV) is rapidly detected in the airways by the immune system, with resident parenchymal cells and leukocytes orchestrating viral sensing and the induction of antiviral inflammatory responses. The airways are innervated by heterogenous populations of vagal sensory neurons which also play an important role in pulmonary defense. How these neurons respond to IAV respiratory infection remains unclear. Here, we use a murine model to provide the first evidence that vagal sensory neurons undergo significant transcriptional changes following a respiratory IAV infection. RNA sequencing on vagal sensory ganglia showed that IAV infection induced the expression of many genes associated with an antiviral and pro-inflammatory response

2021-06-20 | GSE161878 | GEO

Transcriptional profiling of individual airway projecting vagal sensory neurons

Project description:Transcriptional profiling of individual airway projecting vagal sensory neurons

| PRJNA554583 | ENA

Comparison of intubation using instruments as Ambu Auragain,fastrach LMA and Blockbuster LMA.

Project description:Intervention1: Tracheal intubation with supraglottic Airway devices: Comparison of tracheal intubation with Ambu AuraGain,fastrach Laryngeal Mask and Blockbuster Laryngeal Mask Airway. Control Intervention1: Ambu AuraGain: Tracheal intubation with Ambu AuraGain Control Intervention2: Fastrach Laryngeal Mask Airway: Tracheal intubation with Fastrach Laryngeal Mask Airway. Control Intervention3: Blockbuster Laryngeal Mask Airway: Tracheal intubation with Blockbuster Laryngeal Mask Airway. Primary outcome(s): First Attempt success rate of tracheal intubation.Timepoint: During intubation Study Design: Randomized, Parallel Group Trial Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Sequentially numbered, sealed, opaque envelopes Blinding and masking:Participant and Outcome Assessor Blinded

| 2605805 | ecrin-mdr-crc

Transcriptional profiling of individual airway projecting vagal sensory neurons

Project description:Mammalian airways and lungs are richly innervated by bronchopulmonary sensory neurons, the vast majority of which are derived from the vagal sensory ganglia. In the present study we set out to perform high coverage single cell RNA sequencing on a population of identified murine bronchopulmonary sensory neurons collected from the vagal sensory ganglia to better define the molecular expression profiles of these cell types. Given the importance of P2X2 in differentiating nodose from jugular sensory neurons, we further aimed to investigate the relationship between transcriptional expression of identified genes and P2X2 expression.

2019-07-16 | GSE134260 | GEO

Brainstem Dbh+ Neurons Control Chronic Allergen-Induced Airway Hyperreactivity

Project description:Exaggerated airway constriction triggered by exposure to irritants such as allergen, also called hyperreactivity, is a hallmark of asthma and can be life-threatening. Aside from immune cells, vagal sensory neurons are important for airway hyperreactivity 1-4. However, the identity and signature of the downstream nodes of this adaptive circuit remains poorly understood. Here we show that Dbh+ neurons in the nucleus of the solitary tract (nTS) of the brainstem, and downstream neurons in the nucleus ambiguus (NA), are both necessary and sufficient for chronic allergen-induced airway hyperreactivity. We found that repeated exposures of mice to inhaled allergen activates nTS neurons in a mast cell-, interleukin 4 (IL-4)- and vagal nerve-dependent manner. Single-nucleus RNA-seq followed by RNAscope quantification of the nTS at baseline and following allergen challenges reveals that a Dbh+ population is preferentially activated. Ablation or chemogenetic inactivation of Dbh+ nTS neurons blunted, while chemogenetic activation promoted hyperreactivity. Viral tracing indicates that Dbh+ nTS neurons, capable of producing norepinephrine, project to the NA, and NA neurons are necessary and sufficient to relay allergen signals to postganglionic neurons that then directly drive airway constriction. Focusing on transmitters, delivery of norepinephrine antagonists to the NA blunted allergen-induced hyperreactivity. Together, these findings provide molecular, anatomical and functional definitions of key nodes of a canonical allergen response circuit. The knowledge opens the possibility of targeting neural modulation as an approach to control allergen-induced airway constriction.

2024-04-15 | GSE200003 | GEO

Brainstem Dbh+ Neurons Control Chronic Allergen-Induced Airway Hyperreactivity

2024-04-15 | GSE211538 | GEO

A vagal-brainstem interoceptive circuit for cough-like defensive behaviors in mice

Project description:Respiratory defensive behaviors, like coughing, play a crucial role in protecting the respiratory system, ensuring its integrity and optimal function. How these critical behaviors are regulated by sensory stimuli within the body remains largely unknown. Here, we show that the nucleus of the solitary tract (NTS) in mice, a key hub in the brain for processing internal sensory signals and mediating interoceptive processes, contains heterogenous neuronal populations that differentially control breathing. Within these subtypes, activation of tachykinin 1 (Tac1) neurons triggers a specific respiratory behavior. Our detailed characterization of respiratory defensive behaviors reveals that these responses are cough-like behaviors. Chemogenetic silencing or genetic ablation of Tac1 neurons significantly reduces cough-like behaviors induced by tussive challenges. These Tac1 neurons receive synaptic inputs from the bronchopulmonary chemosensory and mechanosensory neurons in the vagal ganglion, and directly integrate the medullary regions to control sequential phases of cough-like defensive behaviors. We propose that these Tac1 neurons are a key component of the airway-vagal-brain neural circuit that controls cough-like defensive behaviors in mice, and they coordinate the downstream modular circuits to elicit the sequential motor pattern of forceful expiratory responses.

2024-06-05 | GSE268741 | GEO

Activation of a nerve injury transcriptional signature in airway-innervating sensory neurons after lipopolysaccharide induced lung inflammation III

Project description:While the inflammatory immune response of the lung to allergens and pathogens has been extensively studied, little is known about how sensory nerves change in response to an inflammatory insult within the organ they innervate. In our study we describe the collection of vagal sensory neurons innervating the mouse lung, labelled with a retrograde fluorescent tracer instilled into the airways, and the analysis of their transcriptomes by RNAseq. We also determined transcriptomes of the complete sensory ganglia (vagal, trigeminal, DRG) for comparison. We identified transcripts of genes exclusively expressed in vagal nerves, and not in any other sensory nerve type or any other organ. These include unique ion channels, G-protein coupled receptors and several transcripts of unknown function.

2020-03-15 | GSE141399 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data