Olfactory sensitivity to odorant molecules is a complex biological function influenced by both endogenous factors, such as genetic background and physiological state, and exogenous factors, such as environmental conditions. In animals, this vital ability is mediated by olfactory sensory neurons (OSNs), which are distributed across several specialized olfactory subsystems depending on the species. Using the phosphorylation of the ribosomal protein S6 (rpS6) in OSNs following sensory stimulation, we developed an ex vivo assay allowing the simultaneous conditioning and odorant stimulation of different mouse olfactory subsystems, including the main olfactory epithelium, the vomeronasal organ, and the Grueneberg ganglion. This approach enabled us to observe odorant-induced neuronal activity within the different olfactory subsystems and to demonstrate the impact of environmental conditioning, such as temperature variations, on olfactory sensitivity, specifically in the Grueneberg ganglion. We further applied our rpS6-based assay to the human olfactory system and demonstrated its feasibility. Our findings show that analyzing rpS6 signal intensity is a robust and highly reproducible indicator of neuronal activity across various olfactory systems, while avoiding stress and some experimental limitations associated with in vivo exposure. The potential extension of this assay to other conditioning paradigms and olfactory systems, as well as its application to other animal species, including human olfactory diagnostics, is also discussed.
- MeSH
- čich fyziologie MeSH
- čichová sliznice metabolismus MeSH
- čichové buňky * metabolismus fyziologie MeSH
- fosforylace MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- odoranty analýza MeSH
- ribozomální protein S6 * metabolismus MeSH
- vomeronazální orgán metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single-cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species-specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale.
The peripheral branch of sensory dorsal root ganglion (DRG) neurons regenerates readily after injury unlike their central branch in the spinal cord. However, extensive regeneration and reconnection of sensory axons in the spinal cord can be driven by the expression of α9 integrin and its activator kindlin-1 (α9k1), which enable axons to interact with tenascin-C. To elucidate the mechanisms and downstream pathways affected by activated integrin expression and central regeneration, we conducted transcriptomic analyses of adult male rat DRG sensory neurons transduced with α9k1, and controls, with and without axotomy of the central branch. Expression of α9k1 without the central axotomy led to upregulation of a known PNS regeneration program, including many genes associated with peripheral nerve regeneration. Coupling α9k1 treatment with dorsal root axotomy led to extensive central axonal regeneration. In addition to the program upregulated by α9k1 expression, regeneration in the spinal cord led to expression of a distinctive CNS regeneration program, including genes associated with ubiquitination, autophagy, endoplasmic reticulum (ER), trafficking, and signaling. Pharmacological inhibition of these processes blocked the regeneration of axons from DRGs and human iPSC-derived sensory neurons, validating their causal contributions to sensory regeneration. This CNS regeneration-associated program showed little correlation with either embryonic development or PNS regeneration programs. Potential transcriptional drivers of this CNS program coupled to regeneration include Mef2a, Runx3, E2f4, and Yy1. Signaling from integrins primes sensory neurons for regeneration, but their axon growth in the CNS is associated with an additional distinctive program that differs from that involved in PNS regeneration.SIGNIFICANCE STATEMENT Restoration of neurologic function after spinal cord injury has yet to be achieved in human patients. To accomplish this, severed nerve fibers must be made to regenerate. Reconstruction of nerve pathways has not been possible, but recently, a method for stimulating long-distance axon regeneration of sensory fibers in rodents has been developed. This research uses profiling of messenger RNAs in the regenerating sensory neurons to discover which mechanisms are activated. This study shows that the regenerating neurons initiate a novel CNS regeneration program which includes molecular transport, autophagy, ubiquitination, and modulation of the endoplasmic reticulum (ER). The study identifies mechanisms that neurons need to activate to regenerate their nerve fibers.
- MeSH
- axony * fyziologie MeSH
- integriny metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mícha metabolismus MeSH
- nervové receptory fyziologie MeSH
- poranění míchy * terapie metabolismus MeSH
- potkani Sprague-Dawley MeSH
- regenerace nervu fyziologie MeSH
- spinální ganglia metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- lidé MeSH
- nervové receptory fyziologie MeSH
- nocicepce * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Obranný mechanizmus dýchacích ciest je zabezpečovaný aktiváciou vagových aferentných nervových zakončení. Tieto nervy sú aktivované mechanickými stimulmi prostredníctvom mechanosenzitívnych Aβ vlákien, ktoré sa delia na pomaly sa adaptujúce (SARs) a rýchlo sa adaptujúce receptory pľúcneho rozpätia (RARs). K mechanosenzitívnym vláknam sú priradené aj nodózne A-delta vlákna, ktoré sprostredkovávajú kašľový reflex. Chemická aktivácia je zabezpečená interakciou chemických látok so špecifickými receptormi. C-vlákna sú vysoko citlivé na priamu chemickú stimuláciu dosiahnutú aktiváciou ligandom riadených iónových kanálov. Vzhľadom na veľký vplyv a mechanizmy vagových aferentných nervov je pravdepodobné, že neprimeraná aktivácia týchto nervových zakončení môže spôsobiť príznaky respiračných ochorení, napr. kašeľ, dyspnoe alebo hyperreaktivitu dýchacích ciest. Cieľom tohto prehľadového článku je zhrnúť fyziológiu aferentných nervov dýchacích ciest a poukázať na úlohu dysfunkcie vagových senzorických nervov v patogenéze niektorých respiračných ochorení. Pochopenie týchto mechanizmov môže priniesť nové terapeutické stratégie u pacientov s ochoreniami dýchacích ciest.
Defensive airway mechanism is ensured by activation of vagal afferent nerve fibers. These nerves can be activated mechanically mainly through mechanosensitive Aβ fibers, which are divided into slowly adapting (SARs) and rapidly adapting stretch receptors (RARs). Nodose A-delta fibers that mediates the cough reflex are also associated with mechanosensitive fibers. Chemical activation is provided by interaction of chemical substances with specific receptors. C-fibers are highly sensitive to direct chemical stimulation accomplished by activation of ligand-gated ion channels. According to the large influence and mechanisms of vagal afferent nerves, there is a probability that inappropriate activity of these nerve endings can cause the symptoms of the respiratory diseases, e.g. cough, dyspnoea or airway hyperreactivity. The aim of this review is to summarize physiology of airway afferent nerves and point out the role of vagal sensory nerves dysfunction in the pathogenesis of some respiratory diseases. The understanding of those mechanisms could result in new therapeutic strategies in patients with airway-related pathology.
- MeSH
- aferentní nervové dráhy * fyziologie patofyziologie MeSH
- COVID-19 patofyziologie patologie MeSH
- dýchací soustava * inervace patofyziologie MeSH
- fyziologie dýchací soustavy MeSH
- kašel etiologie patofyziologie MeSH
- lidé MeSH
- nervová vlákna fyziologie MeSH
- nervové receptory klasifikace patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Different types of spiral ganglion neurons (SGNs) are essential for auditory perception by transmitting complex auditory information from hair cells (HCs) to the brain. Here, we use deep, single cell transcriptomics to study the molecular mechanisms that govern their identity and organization in mice. We identify a core set of temporally patterned genes and gene regulatory networks that may contribute to the diversification of SGNs through sequential binary decisions and demonstrate a role for NEUROD1 in driving specification of a Ic-SGN phenotype. We also find that each trajectory of the decision tree is defined by initial co-expression of alternative subtype molecular controls followed by gradual shifts toward cell fate resolution. Finally, analysis of both developing SGN and HC types reveals cell-cell signaling potentially playing a role in the differentiation of SGNs. Our results indicate that SGN identities are drafted prior to birth and reveal molecular principles that shape their differentiation and will facilitate studies of their development, physiology, and dysfunction.
- MeSH
- buněčná diferenciace genetika MeSH
- ganglion spirale * MeSH
- myši MeSH
- neurony * metabolismus MeSH
- RNA metabolismus MeSH
- vláskové buňky metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chronická bolest etiologie rehabilitace MeSH
- fascie * anatomie a histologie patologie MeSH
- fibróza etiologie komplikace terapie MeSH
- fyzioterapie (techniky) MeSH
- kineziologie aplikovaná MeSH
- lidé MeSH
- nociceptory fyziologie MeSH
- pánevní bolest * etiologie rehabilitace MeSH
- přenesená bolest terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- senzitivní dráhy,
- MeSH
- čití, cítění * fyziologie MeSH
- lidé MeSH
- mechanoreceptory fyziologie MeSH
- nervové dráhy anatomie a histologie fyziologie MeSH
- nocicepce fyziologie MeSH
- propriocepce fyziologie MeSH
- vnímání teploty fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
