Similar Datasets
Project description:Sensory neurons of the vagal ganglia (VG) innervate lungs and play a critical role in maintaining airway homeostasis. However, specific VG neurons that innervate lungs, and mechanisms by which these neurons sense and respond to airway insults, are not well understood. Here, we identify a subpopulation of lung-innervating VG neurons defined by their expression of TMC3. Single cell transcriptomics illuminated several subpopulations of TMC3+ VGs afferents, revealing distinct Piezo2 and Trpv1-expressing subclusters. Furthermore, TMC3 deficiency in VG neurons leads to global and subcluster specific transcriptional changes involved in metabolic and ion channel function. Importantly, we show that broncho-constriction and dilation can be modulated through inhibition or activation of TMC3+ VG neurons with a direct impact on lung tidal volume. Together, our data show that TMC3 is a marker of specific lung-innervating neurons and may play a pivotal role in maintaining fundamental inspiratory and expiratory processes.
2025-12-31 | GSE241083 | GEO
Project description:Sensory neurons of the vagal ganglia (VG) innervate lungs and play a critical role in maintaining airway homeostasis. However, specific VG neurons that innervate lungs, and mechanisms by which these neurons sense and respond to airway insults, are not well understood. Here, we identify a subpopulation of lung-innervating VG neurons defined by their expression of TMC3. Single cell transcriptomics illuminated several subpopulations of TMC3+ VGs afferents, revealing distinct Piezo2 and Trpv1-expressing subclusters. Furthermore, TMC3 deficiency in VG neurons leads to global and subcluster specific transcriptional changes involved in metabolic and ion channel function. Importantly, we show that broncho-constriction and dilation can be modulated through inhibition or activation of TMC3+ VG neurons with a direct impact on lung tidal volume. Together, our data show that TMC3 is a marker of specific lung-innervating neurons and may play a pivotal role in maintaining fundamental inspiratory and expiratory processes.
2025-12-31 | GSE232496 | GEO
Project description:Lung-innervating neurons expressing TMC3 control broncho-constriction and dilation with direct impact on lung tidal volume
| PRJNA1016470 | ENA
Project description:Lung-innervating neurons expressing TMC3 control broncho-constriction and dilation with direct impact on lung tidal volume (scRNA-Seq)
| PRJNA1006374 | ENA
Project description:Lung-innervating neurons expressing TMC3 control broncho-constriction and dilation with direct impact on lung tidal volume (RNA-Seq)
| PRJNA972451 | ENA
Project description:Toothache is a common painful consequence of damage to the teeth, particularly when coupled to infection. Clinical restoration of tooth integrity, sometimes involving physical and chemical sterilization of the tooth with nerve fiber ablation (i.e., endodontic therapy), generally alleviates pain and allows long-lasting dental function. These observations raise questions regarding the biological role of tooth-innervating fibers. Here, we determined the transcriptomic diversity of the sensory neurons that can be retrogradely labeled from mouse molar teeth. Our results demonstrate that individual molars are each targeted by a dedicated population of about 50 specialized trigeminal neurons. Transcriptomic profiling identifies the majority of these as expressing markers of fast-conducting neurons, with about two-thirds containing nociceptive markers. Our data provide a new view of dental innervation, extending previous reports that used candidate gene approaches. Importantly, almost all retrogradely labeled neurons, including nociceptors, express the recently characterized mechanosensor Piezo2, an ion channel that endows cells with sensitivity to gentle touch. Intriguingly, about a quarter of the labeled neurons do not appear to be nociceptors, perhaps insinuating a role for them in discriminative touch. We hypothesize that dental neurons are capable of providing mechanosensitive information to drive rapid behavioral responses and protect teeth from damage. Damage to the teeth and exposure of the large population of molar nociceptors may trigger prolonged or abnormal activation driving toothache. Future studies examining the responses of these transcriptomically defined classes of neurons will help define their significance in oral sensation.
| S-EPMC7684839 | biostudies-literature
Project description:Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes Gram-negative lung infections and fatal pneumonic sepsis for which limited therapeutic options are available. The lungs are densely innervated by nociceptor sensory neurons that mediate breathing, cough, and bronchoconstriction. The role of nociceptors in defense against Gram-negative lung pathogens is unknown. Here, we found that lung-innervating nociceptors promote CRKP pneumonia and pneumonic sepsis. Ablation of nociceptors in mice increased lung CRKP clearance, suppressed trans-alveolar dissemination of CRKP, and protected mice from hypothermia and death. Furthermore, ablation of nociceptors enhanced the recruitment of neutrophils and Ly6Chi monocytes and cytokine induction. Depletion of Ly6Chi monocytes, but not of neutrophils, abrogated lung and extrapulmonary CRKP clearance in ablated mice, suggesting that Ly6Chi monocytes are a critical cellular population to regulate pneumonic sepsis. Further, neuropeptide calcitonin gene-related peptide suppressed the induction of reactive oxygen species in Ly6Chi monocytes and their CRKP-killing abilities. Targeting nociceptor signaling could be a therapeutic approach for treating multidrug-resistant Gram-negative infection and pneumonic sepsis.
| S-EPMC11378917 | biostudies-literature
Project description:The physical properties of events are known to modulate perceived time. This study tested the effect of different quantitative (walking speed) and qualitative (walking-forward vs. walking-backward) features of observed motion on time perception in three complementary experiments. Participants were tested in the temporal discrimination (bisection) task, in which they were asked to categorize durations of walking animations as "short" or "long." We predicted the faster observed walking to speed up temporal integration and thereby to shift the point of subjective equality leftward, and this effect to increase monotonically with increasing walking speed. To this end, we tested participants with two different ranges of walking speeds in Experiment 1 and 2 and observed a parametric effect of walking speed on perceived time irrespective of the direction of walking (forward vs. rewound forward walking). Experiment 3 contained a more plausible backward walking animation compared to the rewound walking animation used in Experiments 1 and 2 (as validated based on independent subjective ratings). The effect of walking-speed and the lack of the effect of walking direction on perceived time were replicated in Experiment 3. Our results suggest a strong link between the speed but not the direction of perceived biological motion and subjective time.
| S-EPMC6309241 | biostudies-literature
Project description:Afferent vagal neurons convey gut-brain signals related to the mechanical and chemical sensing of nutrients, with the latter also mediated by gut hormones secreted from enteroendocrine cells. Cell bodies of these neurons are located in the nodose ganglia (NG), with the right NG playing a key role in metabolic regulation. Notably, glucagon-like peptide-1 receptor (GLP1R) neurons primarily innervate the muscle layer of the stomach, distant from glucagon-like peptide-1 (GLP-1)-secreting gut cells. However, the co-expression of gut hormone receptors in these NG neurons remains unclear. Using RNAscope combined with immunohistochemistry, we confirmed GLP1R expression in a large population of NG neurons, with Glp1r, cholecystokinin A receptor (Cckar), and Neuropeptide Y Y2 Receptor (Npy2r) being more highly expressed in the right NG, while neurotensin receptor 1 (Ntsr), G protein-coupled receptor (Gpr65), and 5-hydroxytryptamine receptor 3A (5ht3a) showed equal expressions in the left and right NG. Co-expression analysis demonstrated the following: (i) most Glp1r, Cckar, and Npy2r neurons co-expressed all three receptors; (ii) nearly all Ntsr1- and Gpr65-positive neurons co-expressed both receptors; and (iii) 5ht3a was expressed in subpopulations of all peptide-hormone-receptor-positive neurons. Retrograde labeling demonstrated that the anterior part of the stomach was preferentially innervated by the left NG, while the right NG innervated the posterior part. The entire gastrointestinal (GI) tract, including the distal colon, was strongly innervated by NG neurons. Most importantly, dual retrograde labeling with two distinct tracers identified a population of neurons co-expressing Glp1r, Cckar, and Npy2r that innervated both the stomach and the colon. Thus, neurons co-expressing GLP-1, cholecystokinin (CCK), and peptide YY (PYY) receptors, predominantly found in the right NG, sample chemical, nutrient-induced signals along the entire GI tract and likely integrate these with mechanical signals from the stomach.
| S-EPMC11899847 | biostudies-literature
Project description:The lungs and the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). Whereas the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNA sequencing (RNA-seq) in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting, we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program, leading to increased expression of gene products such as the G protein-coupled receptor Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG, and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induces a nerve injury-related state, changing vagal excitability.
| S-EPMC7272742 | biostudies-literature