Cell Heavyweights . . . Pioneering new directions, the first discovery was made by only about 100 neurons, dominating coughing, swallowing and other defensive reactions.

Inature sensory neurons activate defense reflex to ensure airway integrity. However, the related sensory pathways are still poorly understood.on April 6, 2020, Stephen D. liberles team of Harvard Medical School published a research paper entitled "an airway protection program revealed by sweeping genetic control of vagal affairs" online on cell. The study found that the rare pharyngeal nerve innervating nerve (about 100 neurons per mouse) can protect the respiratory tract from attack.the genetic tools used in this study cover a wide range of vagal / glossopharyngeal sensory neuron maps.the photogenetic activation of p2ry1 neurons in the vagus nerve causes a coordinated airway defense program - apnea, vocal cord adduction, swallowing and expiratory reflex.the absence of p2ry1 neurons in the vagus nerve eliminated the protective response to laryngeal water and acid stimulation.the anatomical map shows many types of laryngeal terminals. P2ry1 neurons form small body terminals with laryngeal taste buds.epithelial cells are the main airway outposts and communicate with the second-order p2ry1 neurons through ATP.these findings provide insights into the mechanism of vagal airway defense and the general molecular / genetic roadmap.the vagus nerve and other cranial nerves ensure the integrity of several major physiological systems.the peripheral sensory neurons monitor many important parameters, such as blood pressure, airway volume, gastric distension and circulating oxygen level. If a potential imbalance harmful to balance is detected, the neural circuit will be involved in initiating corrective physiological and behavioral responses.the monitoring range of neurons in internal organs is wide, but it is not fully drawn. So far, many neuron protection measures may still be hidden.in addition, organ to brain communication disorders can be fatal.one of the most basic functions of the vagus nerve is to provide the first line of defense to protect the airway from injury.reflex defects in the upper respiratory tract cause some of the most common and serious clinical problems associated with aging, including dysphagia, weight loss, asphyxia, language disorders and respiratory tract infections.in addition, hyperactivity or allergy of neurons in the upper respiratory tract may lead to asthma, chronic cough and sudden infant death syndrome (SIDS).swallowing and expiratory reflex (picture source cell) caused by pharyngeal stimulation and illumination. The larynx is the gateway to the respiratory system and a hot spot of neuronal innervation.the larynx is adjacent to the digestive tract, and the food and water ingested and gastric contents discharged must pass through the larynx and not through the airway. the complex laryngeal neural network protects the respiratory tract from invasion by causing characteristic occlusion and expulsion reflex. for example, each swallowing can cause reflexive reactions, including (1) stopping inhalation to prevent lung aspiration; (2) vocal cord adduction; and (3) closing the laryngeal vestibule by raising hyoid bone and descending epiglottis. if the foreign body does enter the respiratory tract, it causes secondary clearance reflexes, including coughing (in some species), expiratory reflex and swallowing. the vagus nerve innervates the upper respiratory tract through the branches of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN). the internal branches of the superior laryngeal nerve (SLN) provide the main sensory innervation from the vocal cord to the epiglottis and the tail pharynx. on the contrary, the afferent of recurrent laryngeal nerve (RLN) is dominant below the vocal cord, and the trachea and lung are densely innervated. nerve injury or short-term application of local anesthetics can lead to loss of upper laryngeal nerve (SLN), resulting in dysphagia, incomplete closure of the larynx and the risk of airway aspiration. electrical stimulation of the superior laryngeal nerve (SLN) has respiratory protective characteristics, including cough, apnea, vocal cord adduction and imaginary swallowing. these studies emphasize the general importance of neuronal feedback for airway protection, but do not differentiate the contribution of various vagal subtypes or the molecular mechanisms they employ. p2ry1 neuron mediated responses to laryngeal water and acid stimulation (picture source cell) have described a variety of laryngeal sensory terminals, including submucosal and epithelial free ends, red blood cell ends, cough receptors and taste buds near the terminals. however, different terminal types usually show overlapping areas of innervation in the larynx, and there is a lack of consistent anatomical terminology. as a result, previous descriptors may refer to the same end type redundantly. the researchers believe that genetic tools may provide more consistency throughout the study, and also allow specific functional manipulation to address the sensory effects of different laryngeal ends. neural recordings showed that sensory neurons in the larynx detected a variety of mechanical and chemical stimuli, including (1) water, salt and pharyngeal / laryngeal pressures produced by food and drink intake; (2) acids, bile and esophageal forces produced by gastric reflux; and (3) invasive threats such as pathogens and irritants such as smoke, oxidants, and dust particles. various irritant and pathogen detection mechanisms have been proposed, but little is known about the diversity and organization of sensory pathways to protect the respiratory tract from food, drink and gastric reflux. water, salt, acid and force stimulate SLN and also cause defensive reflexes including apnea, vocal cord adduction, pharyngeal swallowing and coughing. the response of larynx to water is very strong, but the primary sensory cells are not clear. Br / > in addition, it is not clear whether the laryngeal epithelial cells play the role of primary or secondary sensory neurons, such as those in the upper respiratory tract. here, researchers use molecular and genetic methods to gain insight into the sensory pathways of the upper respiratory tract. single cell RNA sequencing revealed significant diversity of vagal afferent, and obtained CRE mice to carry out genetic control on most neuronal subtypes in the form of single or small clusters, thus realizing the connection between cell identity, terminal morphology, sensory response and physiological function. cell type specific photogenetic studies have shown that the rare vagus p2ry1 neurons (about 100 in each mouse) cause a series of airway protective responses, including expiratory reflex, vocal cord adduction, apnea and imaginary swallowing. in addition, the loss of p2ry1 neurons in the vagus nerve impaired the defense response to acid and water (rather than salt or force) to throat stress. anatomic tracing guided by genetics showed that p2ry1 neurons of vagus nerve innervated the laryngeal epithelium intensively and closely juxtaposed the taste buds of larynx. the photogenetic activation of epithelial cells mimics the chemosensory reflex of the larynx, which is lost in gene knockout mice lacking ionic purinergic receptors. these findings provide insights into the mechanism of vagal airway defense and the general molecular / genetic roadmap. reference message: