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BMC Biology Aug 2021In the olfactory system, odorant receptors (ORs) expressed at the cell membrane of olfactory sensory neurons detect odorants and direct sensory axons toward precise... (Review)
Review
In the olfactory system, odorant receptors (ORs) expressed at the cell membrane of olfactory sensory neurons detect odorants and direct sensory axons toward precise target locations in the brain, reflected in the presence of olfactory sensory maps. This dual role of ORs is corroborated by their subcellular expression both in cilia, where they bind odorants, and at axon terminals, a location suitable for axon guidance cues. Here, we provide an overview and discuss previous work on the role of ORs in establishing the topographic organization of the olfactory system and recent findings on the mechanisms of activation and function of axonal ORs.
Topics: Axons; Odorants; Olfactory Bulb; Olfactory Receptor Neurons; Receptors, Odorant; Smell
PubMed: 34452614
DOI: 10.1186/s12915-021-01116-y -
Proceedings of the National Academy of... Mar 2022SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain...
SignificanceDespite the identification of neural circuits and circulating hormones in olfactory regulation, the peripheral targets for olfactory modulation remain relatively unexplored. Here we show that dopamine D2 receptor (DRD2) is expressed in the cilia and somata of mature olfactory sensory neurons (OSNs), while nasal dopamine (DA) is mainly released from the sympathetic nerve terminals, which innervate the mouse olfactory mucosa (OM). We further demonstrate that DA-DRD2 signaling in the nose plays important roles in regulating olfactory function using genetic and pharmacological approaches. Moreover, the local DA synthesis in mouse OM is reduced during hunger, which contributes to starvation-induced olfactory enhancement. Altogether, we demonstrate that nasal DA and DRD2 receptor can serve as the potential peripheral targets for olfactory modulation.
Topics: Animals; Dopamine; Dopamine D2 Receptor Antagonists; Humans; Mice; Olfactory Receptor Neurons; Receptors, Dopamine D2; Signal Transduction; Smell
PubMed: 35263227
DOI: 10.1073/pnas.2118570119 -
Cell Dec 2021Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then...
Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.
Topics: Animals; Brain; Gene Expression Regulation; Mice, Inbred C57BL; Mice, Knockout; Odorants; Olfactory Bulb; Olfactory Receptor Neurons; Receptors, Odorant; Sensation; Transcription, Genetic; Transcriptome; Mice
PubMed: 34879231
DOI: 10.1016/j.cell.2021.11.022 -
The Journal of General Physiology Apr 2023JGP study (Takeuchi and Kurahashi. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202213165) reveals that segregation of signals within sensory cilia allows Ca2+ to...
JGP study (Takeuchi and Kurahashi. 2023. J. Gen. Physiol.https://doi.org/10.1085/jgp.202213165) reveals that segregation of signals within sensory cilia allows Ca2+ to play opposing roles in olfactory signal transduction.
Topics: Olfactory Receptor Neurons; Cilia; Calcium; Signal Transduction; Smell
PubMed: 36946993
DOI: 10.1085/jgp.202313378 -
The Journal of Neuroscience : the... May 2021odorant receptors (Ors) are ligand gated ion channels composed of a common receptor subunit Or co-receptor (ORCO) and one of 62 "tuning" receptor subunits that confer...
odorant receptors (Ors) are ligand gated ion channels composed of a common receptor subunit Or co-receptor (ORCO) and one of 62 "tuning" receptor subunits that confer odorant specificity to olfactory neuron responses. Like other sensory systems studied to date, exposing olfactory neurons to activating ligands results in reduced responses to subsequent exposures through a process called desensitization. We recently showed that phosphorylation of serine 289 on the common Or subunit ORCO is required for normal peak olfactory neuron responses. Dephosphorylation of this residue occurs on prolonged odorant exposure, and underlies the slow modulation of olfactory neuron responses we term "slow desensitization." Slow desensitization results in the reduction of peak olfactory neuron responses and flattening of dose-response curves, implicating changes in ORCO phosphorylation state as an important modulator of olfactory neuron responses. Here, we report the identification of the primary kinase responsible for ORCO phosphorylation, PKC98E. Antiserum localizes the kinase to the dendrites of the olfactory neurons. Deletion of the kinase from olfactory neurons in the naive state (the absence of prolonged odor exposure) reduces ORCO phosphorylation and reduces peak odorant responses without altering receptor localization or expression levels. Genetic rescue with a predicted to be constitutively active restores ORCO S289 phosphorylation and olfactory neuron sensitivity to the mutants in the naive state. However, the dominant kinase is defective for slow desensitization. Together, these findings reveal that PKC98E is an important regulator of ORCO receptors and olfactory neuron function. We have identified PKC98E as the kinase responsible for phosphorylation of the odorant receptor co-receptor (ORCO) at S289 that is required for normal odorant response kinetics of olfactory neurons. This is a significant step toward revealing the enzymology underlying the regulation of odorant response regulation in insects.
Topics: Animals; Dendrites; Dose-Response Relationship, Drug; Drosophila Proteins; Drosophila melanogaster; Electrophysiological Phenomena; Gene Deletion; Mutation; Odorants; Olfactory Receptor Neurons; Phosphorylation; Protein Kinase C; RNA Interference; Receptors, Odorant
PubMed: 33789918
DOI: 10.1523/JNEUROSCI.3019-20.2021 -
BMC Biology Sep 2022Ray-finned fishes (Actinopterygii) perceive their environment through a range of sensory modalities, including olfaction. Anatomical diversity of the olfactory organ...
BACKGROUND
Ray-finned fishes (Actinopterygii) perceive their environment through a range of sensory modalities, including olfaction. Anatomical diversity of the olfactory organ suggests that olfaction is differentially important among species. To explore this topic, we studied the evolutionary dynamics of the four main gene families (OR, TAAR, ORA/VR1 and OlfC/VR2) coding for olfactory receptors in 185 species of ray-finned fishes.
RESULTS
The large variation in the number of functional genes, between 28 in the ocean sunfish Mola mola and 1317 in the reedfish Erpetoichthys calabaricus, is the result of parallel expansions and contractions of the four main gene families. Several ancient and independent simplifications of the olfactory organ are associated with massive gene losses. In contrast, Polypteriformes, which have a unique and complex olfactory organ, have almost twice as many olfactory receptor genes as any other ray-finned fish.
CONCLUSIONS
We document a functional link between morphology of the olfactory organ and richness of the olfactory receptor repertoire. Further, our results demonstrate that the genomic underpinning of olfaction in ray-finned fishes is heterogeneous and presents a dynamic pattern of evolutionary expansions, simplifications, and reacquisitions.
Topics: Animals; Evolution, Molecular; Fishes; Genome; Olfactory Receptor Neurons; Phylogeny; Receptors, Odorant
PubMed: 36050670
DOI: 10.1186/s12915-022-01397-x -
Journal of Virology Nov 2021Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the...
Herpesvirus genomes show abundant evidence of past recombination. Its functional importance is unknown. A key question is whether recombinant viruses can outpace the immunity induced by their parents to reach higher loads. We tested this by coinfecting mice with attenuated mutants of murid herpesvirus 4 (MuHV-4). Infection by the natural olfactory route routinely allowed mutant viruses to reconstitute wild-type genotypes and reach normal viral loads. Lung coinfections rescued much less well. Attenuated murine cytomegalovirus mutants similarly showed recombinational rescue via the nose but not the lungs. These infections spread similarly, so route-specific rescue implied that recombination occurred close to the olfactory entry site. Rescue of replication-deficient MuHV-4 confirmed this, showing that coinfection occurred in the first encountered olfactory cells. This worked even with asynchronous inoculation, implying that a defective virus can wait here for later rescue. Virions entering the nose get caught on respiratory mucus, which the respiratory epithelial cilia push back toward the olfactory surface. Early infection was correspondingly focused on the anterior olfactory edge. Thus, by concentrating incoming infection into a small area, olfactory entry seems to promote functionally significant recombination. All organisms depend on genetic diversity to cope with environmental change. Small viruses rely on frequent point mutations. This is harder for herpesviruses because they have larger genomes. Recombination provides another means of genetic optimization. Human herpesviruses often coinfect, and they show evidence of past recombination, but whether this is rare and incidental or functionally important is unknown. We showed that herpesviruses entering mice via the natural olfactory route meet reliably enough for recombination routinely to repair crippling mutations and restore normal viral loads. It appeared to occur in the first encountered olfactory cells and reflected a concentration of infection at the anterior olfactory edge. Thus, natural host entry incorporates a significant capacity for herpesvirus recombination.
Topics: Animals; Herpesviridae; Herpesviridae Infections; Lung; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mutation; Nose; Olfactory Mucosa; Open Reading Frames; Receptors, Odorant; Recombination, Genetic; Rhadinovirus; Virus Internalization
PubMed: 34523965
DOI: 10.1128/JVI.01555-21 -
Frontiers in Immunology 2022In the vertebrate olfactory tract new neurons are continuously produced throughout life. It is widely believed that neurogenesis contributes to learning and memory and...
In the vertebrate olfactory tract new neurons are continuously produced throughout life. It is widely believed that neurogenesis contributes to learning and memory and can be regulated by immune signaling molecules. Proteins originally identified in the immune system have subsequently been localized to the developing and adult nervous system. Previously, we have shown that olfactory imprinting, a specific type of long-term memory, is correlated with a transcriptional response in the olfactory organs that include up-regulation of genes associated with the immune system. To better understand the immune architecture of the olfactory organs we made use of cell-specific fluorescent reporter lines in dissected, intact adult brains of zebrafish to examine the association of the olfactory sensory neurons with neutrophils and blood-lymphatic vasculature. Surprisingly, the olfactory organs contained the only neutrophil populations observed in the brain; these neutrophils were localized in the neural epithelia and were associated with the extensive blood vasculature of the olfactory organs. Damage to the olfactory epithelia resulted in a rapid increase of neutrophils both within the olfactory organs as well as the central nervous system. Analysis of cell division during and after damage showed an increase in BrdU labeling in the neural epithelia and a subset of the neutrophils. Our results reveal a unique population of neutrophils in the olfactory organs that are associated with both the olfactory epithelia and the lymphatic vasculature suggesting a dual olfactory-immune function for this unique sensory system.
Topics: Animals; Neutrophils; Olfactory Bulb; Olfactory Mucosa; Olfactory Receptor Neurons; Zebrafish
PubMed: 35693773
DOI: 10.3389/fimmu.2022.881702 -
Current Biology : CB Jun 2023The olfactory system uses hundreds of odorant receptors (ORs), the largest group of the G-protein-coupled receptor (GPCR) superfamily, to detect a vast array of...
The olfactory system uses hundreds of odorant receptors (ORs), the largest group of the G-protein-coupled receptor (GPCR) superfamily, to detect a vast array of odorants. Each OR is activated by specific odorous ligands, and like other GPCRs, antagonism can block activation of ORs. Recent studies suggest that odorant antagonisms in mixtures influence olfactory neuron activities, but it is unclear how this affects perception of odor mixtures. In this study, we identified a set of human ORs activated by methanethiol and hydrogen sulfide, two potent volatile sulfur malodors, through large-scale heterologous expression. Screening odorants that block OR activation in heterologous cells identified a set of antagonists, including β-ionone. Sensory evaluation in humans revealed that β-ionone reduced the odor intensity and unpleasantness of methanethiol. Additionally, suppression was not observed when methanethiol and β-ionone were introduced simultaneously to different nostrils. Our study supports the hypothesis that odor sensation is altered through antagonistic interactions at the OR level.
Topics: Humans; Odorants; Receptors, Odorant; Smell; Perception; Olfactory Receptor Neurons; Olfactory Perception
PubMed: 37220745
DOI: 10.1016/j.cub.2023.04.072 -
Animals : An Open Access Journal From... May 2022The olfactory mucosa contains olfactory ecto-mesenchymal stem cells (OE-MSCs) which show stemness features, multipotency capabilities, and have a therapeutic potential....
The olfactory mucosa contains olfactory ecto-mesenchymal stem cells (OE-MSCs) which show stemness features, multipotency capabilities, and have a therapeutic potential. The OE-MSCs have already been collected and isolated from various mammals. The aim of this study was to evaluate the feasibility of collecting, purifying and amplifying OE-MSCs from the cat nasal cavity. Four cats were included in the study. Biopsies of olfactory mucosa were performed on anesthetized animals. Then, the olfactory OE-MSCs were isolated, and their stemness features as well as their mesodermal differentiation capabilities were characterized. Olfactory mucosa biopsies were successfully performed in all subjects. From these biopsies, cellular populations were rapidly generated, presenting various stemness features, such as a fibroblast-like morphology, nestin and MAP2 expression, and sphere and colony formation. These cells could differentiate into neural and mesodermal lineages. This report shows for the first time that the isolation of OE-MSCs from cat olfactory mucosa is possible. These cells showed stemness features and multilineage differentiation capabilities, indicating they may be a promising tool for autologous grafts and feline regenerative medicine.
PubMed: 35625130
DOI: 10.3390/ani12101284