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A neuromorphic module of an electronic nose (E‐nose) is demonstrated by hybridizing a chemoresistive gas sensor made of a semiconductor metal oxide (SMO) and a single transistor neuron (1T‐neuron) made of a metal‐oxide‐semiconductor field‐effect transistor (MOSFET). By mimicking a biological olfactory neuron, it simultaneously detects a gas and encoded spike signals for in‐sensor neuromorphic functioning. It identifies an odor source by analyzing the complicated mixed signals using a spiking neural network (SNN). The proposed E‐nose does not require conversion circuits, which are essential for processing the sensory signals between the sensor array and processors in the conventional bulky E‐nose. In addition, they do not have to include a central processing unit (CPU) and memory, which are required for von Neumann computing. The spike transmission of the biological olfactory system, which is known to be the main factor for reducing power consumption, is realized with the SNN for power savings compared to the conventional E‐nose with a deep neural network (DNN). Therefore, the proposed neuromorphic E‐nose is promising for application to Internet of Things (IoT), which demands a highly scalable and energy‐efficient system. As a practical example, it is employed as an electronic sommelier by classifying different types of wines. [ABSTRACT FROM AUTHOR]

The phenomenal sensitivity of the olfactory system and its ability to detect an enormous diversity of olfactory stimuli are to a large extent due to the existence of numerous olfactory receptors. The genes encoding olfactory receptors (OR) form the largest family in mammalian genomes. The defining principle in the model of olfactory information encoding is the "one neuron–one receptor" rule, whereby just one gene of the OR gene family is selected for expression in each of the 107 olfactory neurons located in the olfactory epithelium. Although the physiological appropriateness of the "one neuron–one receptor" principle is undoubted, the rule is essentially hypothetical in nature and has not been verified experimentally to the necessary level. In particular, the question of the epigenetic mechanisms of stochastic, monogenic, and monoallelic expression of OR genes remains open. The results of deep sequencing of the transcriptomes of single cells unexpectedly revealed multireceptor neurons containing transcripts for several OR genes. Does this mean that the rule which more than 25 years ago was believed to be physiologically confirmed, unshakeable, and unarguable does not operate? This review will present different interpretations of results from studies of the transcriptomes of single olfactory neurons which explain the existence of "multireceptor" neurons and their role in the process of olfactory neurogenesis. [ABSTRACT FROM AUTHOR]

Background Coronavirus disease 2019 (COVID-19) is primarily an acute respiratory tract infection. Distinctively, a substantial proportion of COVID-19 patients develop olfactory dysfunction. Especially in young patients, loss of smell can be the first or only symptom. The roles of inflammatory obstruction of the olfactory clefts, inflammatory cytokines affecting olfactory neuronal function, destruction of olfactory neurons or their supporting cells, and direct invasion of olfactory bulbs in causing olfactory dysfunction are uncertain. Methods We investigated the location for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the olfactory epithelium (OE) to the olfactory bulb in golden Syrian hamsters. Results After intranasal inoculation with SARS-CoV-2, inflammatory cell infiltration and proinflammatory cytokine/chemokine responses were detected in the nasal turbinate tissues. The responses peaked between 2 and 4 days postinfection, with the highest viral load detected at day 2 postinfection. In addition to the pseudo-columnar ciliated respiratory epithelial cells, SARS-CoV-2 viral antigens were also detected in the mature olfactory sensory neurons labeled by olfactory marker protein, in the less mature olfactory neurons labeled by neuron-specific class III β-tubulin at the more basal position, and in the sustentacular cells, resulting in apoptosis and severe destruction of the OE. During the entire course of infection, SARS-CoV-2 viral antigens were not detected in the olfactory bulb. Conclusions In addition to acute inflammation at the OE, infection of mature and immature olfactory neurons and the supporting sustentacular cells by SARS-CoV-2 may contribute to the unique olfactory dysfunction related to COVID-19, which is not reported with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

We examined the histopathological changes in the olfactory mucosa of cynomolgus and rhesus macaque models of SARS-CoV-2 infection. SARS-CoV-2 infection induced severe inflammatory changes in the olfactory mucosa. A major histocompatibility complex (MHC) class II molecule, HLA-DR was expressed in macrophage and supporting cells, and melanocytes were increased in olfactory mucosa. Supporting cells and olfactory neurons were infected, and SARS-CoV-2 N protein was detected in the axons of olfactory neurons and in olfactory bulbs. Viral RNA was detected in olfactory bulbs and brain tissues. The olfactory epithelium-olfactory bulb pathway may be important as a route for intracranial infection by SARS-CoV-2. • SARS-CoV-2 infection induces severe inflammatory changes in olfactory mucosa. • Supporting cells, olfactory neurons and olfactory bulbs are infected. • Supporting cells and macrophages express HLA-DR as antigen presenting cells. • Melanocytes increase in the infected olfactory mucosa. • Olfactory epithelium-olfactory bulb pathway as a route for intracranial infection. [ABSTRACT FROM AUTHOR]

The volatile plant compounds (VPC) alter pheromone perception by insects but mixture effects inside insect olfactory landscapes are poorly understood. We measured the activity of receptor neurons tuned to Z7-12Ac (Z7-ORN), a pheromone component, in the antenna and central neurons in male Agrotis ipsilon while exposed to simple or composite backgrounds of a panel of VPCs representative of the odorant variety encountered by a moth. Maps of activities were built using calcium imaging to visualize which areas in antennal lobes (AL) were affected by VPCs. We compared the VPC activity and their impact as backgrounds at antenna and AL levels, individually or in blends. At periphery, VPCs showed differences in their capacity to elicit Z7-ORN firing response that cannot be explained by differences in stimulus intensities because we adjusted concentrations according to vapor pressures. The AL neuronal network, which reformats the ORN input, did not improve pheromone salience. We postulate that the AL network evolved to increase sensitivity and to encode for fast changes of pheromone at some cost for signal extraction. Comparing blends to single compounds indicated that a blend shows the activity of its most active component. VPC salience seems to be more important than background complexity.

Oxaliplatin (OXAL) is regarded as a platinum-based anti-neoplastic agent. However, its perturbations on membrane ionic currents in neurons and neuroendocrine or endocrine cells are largely unclear, though peripheral neuropathy has been noted during its long-term administration. In this study, we investigated how the presence of OXAL and other related compounds can interact with two types of inward currents; namely, hyperpolarization-activated cation current (Ih) and membrane electroporation-induced current (IMEP). OXAL increased the amplitude or activation rate constant of Ih in a concentration-dependent manner with effective EC50 or KD values of 3.2 or 6.4 μM, respectively, in pituitary GH3 cells. The stimulation by this agent of Ih could be attenuated by subsequent addition of ivabradine, protopine, or dexmedetomidine. Cell exposure to OXAL (3 μM) resulted in an approximately 11 mV rightward shift in Ih activation along the voltage axis with minimal changes in the gating charge of the curve. The exposure to OXAL also effected an elevation in area of the voltage-dependent hysteresis elicited by long-lasting triangular ramp. Additionally, its application resulted in an increase in the amplitude of IMEP elicited by large hyperpolarization in GH3 cells with an EC50 value of 1.3 μM. However, in the continued presence of OXAL, further addition of ivabradine, protopine, or dexmedetomidine always resulted in failure to attenuate the OXAL-induced increase of IMEP amplitude effectively. Averaged current-voltage relation of membrane electroporation-induced current (IMEP) was altered in the presence of OXAL. In pituitary R1220 cells, OXAL-stimulated Ih remained effective. In Rolf B1.T olfactory sensory neurons, this agent was also observed to increase IMEP in a concentration-dependent manner. In light of the findings from this study, OXAL-mediated increases of Ih and IMEP may coincide and then synergistically act to increase the amplitude of inward currents, raising the membrane excitability of electrically excitable cells, if similar in vivo findings occur. [ABSTRACT FROM AUTHOR]

Background & objectives: It is well reported that exhaled CO 2 and skin odour from human being assist female mosquitoes to locate human host. Basically, the receptors for this activity are expressed in cpA neurons. In both Aedes aegypti and Anopheles gambiae, this CO 2-sensitive olfactory neuron detects myriad number of chemicals present in human skin. Therefore, manipulation of gustatory receptors housing these neurons may serve as important targets for behavioural intervention. The study was aimed towards virtual screening of small molecules in the analyzed conserved active site residues of gustatory receptor and molecular dynamics simulation study of optimum protein-ligand complex to identify a suitable lead molecule for distracting host-seeking behaviour of mosquitoes. Methods: The conserved residue analysis of gustatory receptor (GR) of Ae. aegypti and An. gambiae was performed. The structure of GR protein from Ae. aegypti was modeled and validated, and then molecular docking was performed to screen 2903 small molecules against the predicted active residues of GR. Further, simulation studies were also carried out to prove protein-ligand stability. Results: The glutamine 154 residue of GR was found to be highly conserved in Ae. aegypti and An. gambiae. Docking results indicated that the dodecanoic acid, 1,2,3-propanetriyl ester (dynasan 112) was interacting with this residue, as it showed better LibDock score than previously reported ethyl acetate used as mosquito repellant. Simulation studies indicated the structural instability of GR protein in docked form with dynasan 112 suggesting its involvement in structural changes. Based on the interaction energies and stability, this compound has been proposed to be used in mosquitoes′ repellant. Interpretation & conclusion: A novel effective odorant acting as inhibitor of GR is proposed based on its stability, docking score, interactions and RMSD, considering ethyl pyruvate as a standard inhibitor. Host preference and host-seeking ability of mosquito vectors play key roles in disease transmission, a clear understanding of these aspects is essential for preventing the spread of the disease.

The mosquito's antenna represents its main olfactory appendage for detecting volatile chemical cues from the environment. Whole-mount fluorescence in situ hybridization of ionotropic receptors (IRs) expressed in the antennae reveals that the antenna might be divisible into proximal and distal functional domains. The number of IR-positive cells appear stereotyped within each antennal segment (flagellomere). Highly expressed odor-tuning IRs exhibit distinct co-localization patterns with the IR coreceptors Ir8a, Ir25a, and Ir76b that might predict their functional properties. Genetic knockin and in vivo functional imaging of IR41c-expressing neurons indicate both odor-induced activation and inhibition in response to select amine compounds. Targeted mutagenesis of IR41c does not abolish behavioral responses to the amine compounds. Our study provides a comprehensive map of IR-expressing neurons in the main olfactory appendage of mosquitoes. These findings show organizing principles of Anopheles IR-expressing neurons, which might underlie their functional contribution to the detection of behaviorally relevant odors. [Display omitted] • Some antennal-expressed IRs are organized into proximal and distal domains • IR coreceptor co-expression patterns offer functional insights into odor detection • IR neuron populations are not changed after blood meal or in aged adults • IR41c-expressing neurons are activated and inhibited by select amine compounds Raji et al. present the spatial organizational pattern of ionotropic receptor (IR) expression in the mosquito antenna. The IR map suggests general odor properties for IR neurons. A knockin of an odor-tuning IR supports the prediction and shows excitatory and inhibitory responses to odors. [ABSTRACT FROM AUTHOR]

In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor gene. By calcium imaging of individual OSNs in intact mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located in the most ventral olfactory receptor zone can mediate distinct signaling pathways when activated by structurally similar ligands. Calcium imaging showed that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4-heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP signaling while heptaldehyde triggered the diacylglycerol pathway. An increase of intracellular calcium evoked by cis-4-heptenal was due to a combination of activation mediated by the adenylate cyclase pathway and suppression generated by phospholipase C signaling. Pharmacological studies demonstrated that novel mechanisms were involved in the phospholipase C-mediated intracellular calcium changes. Binary-mixture studies and cross-adaptation data indicate that three odorants acted on the same olfactory receptor. The feature that an olfactory receptor mediates multiple signaling pathways was specific for Ho-OSNs and not established in another population of OSNs characterized. Our study suggests that distinct signaling pathways triggered by ligand-induced conformational changes of an olfactory receptor constitute a complex information process mechanism in olfactory transduction. This study has important implications beyond olfaction in that it provides insights of plasticity and complexity of G-protein-coupled receptor activation and signal transduction. [ABSTRACT FROM AUTHOR]

Peroxiredoxins (Prdxs) comprise a large family of cysteine-based peroxidases that are involved in a wide variety of physiological processes. At the single-cell level co-expression of Prdxs has not been studied. We performed gene expression profiling in mouse olfactory neurons and found that individual cells express distinct prdxs in multiple combinations. In the case of conventional interpretation of RT-PCR data, differential expression patterns indicate that each olfactory neuron selects specific set of prdxs to express. However, a new concept of stochastic dynamics of gene expression may provide an alternative interpretation of our data. Here we suggest that the lack of synchronization in transcriptional states of individual genes may give rise to temporal shifts in gene expression pattern, thus constituting a plausible source of variability detected at the single-cell level. If so, the olfactory neuron is likely to transcribe genes for each of the six Prdxs yet with entirely different transcriptional phases. Based on the discontinuous mode of gene expression, the composition of Prdx transcripts within a cell may be variable, and therefore, the outcome of gene expression analysis is likely to depend on the moment of cell harvesting. This assumption easily reconciles the apparent discrepancy between transcriptional profiles derived from single cells and from population of cells. [ABSTRACT FROM AUTHOR]

The olfactory signal transduction cascade transforms odor information into electrical signals by a cAMP-based amplification mechanism. The mechanisms underlying the very precise temporal and spatial organization of the relevant signaling components remains poorly understood. Here, we identify, using co-immunoprecipitation experiments, a macromolecular assembly of signal transduction components in mouse olfactory neurons, organized through MUPP1. Disruption of the PDZ signaling complex, through use of an inhibitory peptide, strongly impaired odor responses and changed the activation kinetics of olfactory sensory neurons. In addition, our experiments demonstrate that termination of the response is dependent on PDZ-based scaffolding. These findings provide new insights into the functional organization, and regulation, of olfactory signal transduction. [ABSTRACT FROM AUTHOR]

Highlights: [•] Chemotaxis of C. elegans toward an odor butanone was reduced by removal of NaCl from background. [•] Chemotaxis toward NaCl in a butanone or isoamyl alcohol background was not affected by the background. [•] In NaCl-free background, gustatory neurons ASE suppress the butanone-sensing neuron. [Copyright &y& Elsevier]

Phantosmia, the perception of an odor when there are no odorants in the environment, can be a very debilitating symptom. In the 1960s, Zilstorff reported olfactory distortions could be treated by the topical application of a cocaine solution to the olfactory epithelium. In evaluating this treatment, we observed no long-term benefit using cocaine on 6 patients with phantosmia. Based on our observations, the patient’s olfactory ability was not a determining factor in the initiation or quality of their phantosmia. Following topical cocainization, we observed a remarkable delay of hours to days in the return of olfactory ability, and when cocaine was applied to only 1 nostril, there was a decreased olfactory ability on the noncocainized side. These results may suggest the possibility that phantosmia is related to a central processing problem. [ABSTRACT FROM AUTHOR]

Sex pheromo.ies are intraspecific olfactory signals emitted by one sex to attract a potential mating partner. Behavioural responses to sex pheromones are generally highly stereotyped. However, they can be modulated by experience, as male moths previously exposed to female sex pheromone respond with a lower threshold upon further detection, even after long delays. Here, we address the question of the neural mechanisms underlying such long-term modulation. As previous work has shown increased responses to pheromone in central olfactory neurons, we asked whether brief exposure to the pheromone increases input activity from olfactory receptor neurons. Males pre-exposed to sex pheromone exhibited increased peripheral sensitivity to the main pheromone component. Among nine antennal genes targeted as putatively involved in pheromone reception, one encoding a pheromone-binding protein showed significant upregulation upon exposure. In the primary olfactory centre (antennal lobe), the neural compartment processing the main pheromone component was enlarged after a brief pheromone exposure, thus suggesting enduring structural changes. We hypothesise that higher peripheral sensitivity following pre-exposure leads to increased input to the antennal lobe, thus contributing to the structural and functional reorganization underlying a stable change in behaviour. [ABSTRACT FROM AUTHOR]

Signal transduction depends critically on the spatial localization of protein constituents. A key question in odor transduction is whether chemotransduction proteins organize into discrete molecular complexes throughout olfactory cilia or distribute homogeneously along the ciliary membrane. Our recordings of Ca2+ changes in individual cilia with unprecedented spatial and temporal resolution, by the use of two-photon microscopy, provide solid evidence for Ca2+ microdomains (transducisomes). Dissociated frog olfactory neurons were preloaded with caged-cAMP and fluo-4 acetoxymethyl ester probe Ca2+ indicator. Ca2+ influx through cyclic nucleotide-gated (CNG) channels was evoked by uniformly photoreleasing cAMP, while ciliary Ca2+ was measured. Discrete fluorescence events were clearly resolved. Events were missing in the absence of external Ca2+, consistent with the absence of internal Ca2+ sources. Fluorescence events at individual microdomains resembled single-CNG channel fluctuations in shape, mean duration and kinetics, indicating that transducisomes typically contain one to three CNG channels. Inhibiting the Na+/Ca2+ exchanger or the Ca2+-ATPase prolonged the decay of evoked intraciliary Ca2+ transients, supporting the participation of both transporters in ciliary Ca2+ clearance, and suggesting that both molecules localize close to the CNG channel. Chemosensory transducisomes provide a physical basis for the low amplification and for the linearity of odor responses at low odor concentrations. [ABSTRACT FROM AUTHOR]

The unique ability of mammals to detect and discriminate between thousands of different odorant molecules is governed by the diverse array of olfactory receptors expressed by olfactory sensory neurons in the nasal epithelium. Olfactory receptors consist of seven transmembrane domain G protein-coupled receptors and comprise the largest gene superfamily in the mammalian genome. We found that approximately 30% of olfactory receptors possess a classical post-synaptic density 95, Drosophila discs large, zona-occludens 1 (PDZ) domain binding motif in their C-termini. PDZ domains have been established as sites for protein–protein interaction and play a central role in organizing diverse cell signaling assemblies. In the present study, we show that multi-PDZ domain protein 1 (MUPP1) is expressed in the apical compartment of olfactory sensory neurons. Furthermore, on heterologous co-expression with olfactory sensory neurons, MUPP1 was shown to translocate to the plasma membrane. We found direct interaction of PDZ domains 1 + 2 of MUPP1 with the C-terminus of olfactory receptors in vitro. Moreover, the odorant-elicited calcium response of OR2AG1 showed a prolonged decay in MUPP1 small interfering RNA-treated cells. We have therefore elucidated the first building blocks of the putative ‘olfactosome’, brought together by the scaffolding protein MUPP1, a possible central nucleator of the olfactory response. Structured digital abstract • : OR2AG1 (uniprotkb: ) physically interacts ( ) with MUPP1 (uniprotkb: ) by anti tag coimmunoprecipitation ( ) • , , , : OR2AG1 (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by peptide array ( ) • : mOR283-1 (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by peptide array ( ) • : mOR-EG (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by peptide array ( ) • : h OR3A1 (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by peptide array ( ) • : h OR1D2 (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by peptide array ( ) • : AC3 (uniprotkb: ) and MUPP1 (uniprotkb: ) colocalize ( ) by fluorescence microscopy ( ) • , , : O R2AG1 (uniprotkb: ) binds ( ) to MUPP1 (uniprotkb: ) by pull down ( ) [ABSTRACT FROM AUTHOR]

We report on the identification and characterization of a new cDNA encoding the pheromone-binding protein1 (PxylPBP1) from male antennae of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae). The deduced amino acid sequences of PxylPBP1 revealed a mature protein of 164 amino acids, with six cysteine residues in conserved positions relative to other known PBP. The alignment of the mature PxylPBP1 with other Lepidoptera PBP showed high sequence similarity (70–80%) with other full-length sequences from GenBank. Reverse transcription polymerase chain reaction (PCR) analysis revealed that the PxylPBP1 gene is only expressed in antennae. Real-time PCR further indicated that the expression of PxylPBP1 gene is higher in male moths, and higher in mated moths regardless of gender. The transcription levels of PxylPBP1 gene of unmated male moths reduced with age, and peaked in 4-h-old female moths. [ABSTRACT FROM AUTHOR]

The vertebrate olfactory system has fascinated neurobiologists over the last six decades because of its ability to replace its neurons and synaptic connections continuously throughout adult life, under both physiological and pathological conditions. Among the factors that are proposed to be involved in this regenerative potential, brain-derived neurotrophic factor (BDNF) is a candidate for having an important role in the neuronal turnover in the olfactory epithelium (OE) because of its well-documented neurogenic and trophic effects throughout the nervous system. The aim of the present study was to generate a suitable model to study the participation of BDNF in the recovery of the OE after injury in vivo. We developed an experimental design in which the OE of Rhinella arenarum tadpoles could be easily and selectively damaged by immersing the animals in ZnSO4 solutions of various concentrations for differing time periods. Image analysis of histological sections showed that different combinations of each of these conditions produced statistically different degrees of injury to the olfactory tissue. We also observed that the morphology of the OE was restored within a few days of recovery after ZnSO4 treatment. Immunohistochemical analysis of BDNF was performed with an antiserum whose specificity was confirmed by Western blotting, and which showed drastic changes in the abundance and distribution pattern of this neurotrophin in the damaged olfactory system. Our results thus suggest that BDNF is involved in the regeneration of the OE of amphibian larvae, and that our approach is suitable for further investigations of this topic. [ABSTRACT FROM AUTHOR]

Neural oscillations, which appear in several areas of the nervous system and cover a wide frequency range, are a prominent issue in current neuroscience. Extracellularly recorded oscillations are generally thought to be a manifestation of a neural population with synchronized electrical activity resulting from coupling mechanisms. The vertebrate olfactory neuroepithelium exhibits β-band oscillations, termed peripheral waves (PWs), in their population response to odor stimulation. Here, we examine PWs in the channel catfish and propose that their properties could be explained as the superposition of asynchronous oscillators. Our model shows that the intriguing random pattern of amplitude-modulated PWs could be explained by Rayleigh fading, an interference phenomenon well known in physics and recognizable using statistical methods and signal analysis. We are proposing a mathematical fingerprint to characterize neural signals generated by the addition of random phase oscillators. Our interpretation of PWs as arising from asynchronous oscillators could be generalized to other neuronal populations, because it suggests that neural oscillations, detected in local field potential recordings within a narrow frequency band, do not necessarily originate from synchronization events. [ABSTRACT FROM AUTHOR]

Abstract: Olfactory neurons obtained through nasal biopsy were characterized. Using standard immunohistochemical techniques, nascent, developing, and mature neurons were identified in the tissues obtained. This technique shows that aspects of canine olfactory function may be potentially assessed using a relatively simple and minimally invasive biopsy technique. Such samples provide direct access to neuronal tissue that is otherwise difficult to obtain and assess in living animals. This technique may have potential value to those interested in assessing olfactory abilities in dogs. [Copyright &y& Elsevier]

Behavioral plasticity induced by the integration of two sensory signals, such as associative learning, is an important issue in neuroscience, but its evolutionary origin and diversity have not been explored sufficiently. We report here a new type of such behavioral plasticity, which we call butanone enhancement, in Caenorhabditis elegans adult hermaphrodites: C. elegans specifically enhances chemotaxis to butanone by preexposure to butanone and food. Mutant analysis revealed that this plasticity requires the AWCON olfactory neuron, whose fate is known to be determined by the NSY-1/ASK1 MAPKKK (mitogen-activated protein kinase kinase kinase) cascade as well as the DAF-11 and ODR-1 guanylyl cyclases. These proteins also control many aspects of olfactory sensation/plasticity in AWC neurons and seem to provide appropriate cellular conditions for butanone enhancement in the AWCON neuron. Butanone enhancement also required the functions of Bardet-Biedl syndrome genes in the AWCON neuron but not other genes that control ciliary transport. Furthermore, preexposure to butanone and the odor of food was enough for the enhancement of butanone chemotaxis. These results suggest that the AWCON olfactory neuron may conduct a behavioral plasticity resembling associative learning and that the functions of Bardet-Biedl syndrome genes in sensory cilia may play an important role in this plasticity. [ABSTRACT FROM AUTHOR]

Abstract: Multicellular organisms undergo programmed cell death (PCD) as a mechanism for tissue remodeling during development and tissue renewal throughout adult life. Overdose of some neuronal receptor agonists like glutamate can trigger a PCD process termed excitotoxicity in neurons of the central nervous system. Calcium has an important role in PCD processes, especially in excitotoxicity. Since the normal turnover of olfactory receptor neurons (ORNs) relies, at least in part, on an apoptotic mechanism and odor transduction in ORNs involves an increase in intracellular Ca2+ concentration ([Ca2+]i), we investigated the possibility that long-term exposures to odorants could trigger an excitotoxic process in olfactory epithelial cells (EC). We used single-cell [Ca2+]i determinations and fluorescence microscopy techniques to study the effects of sustained odorant exposures in olfactory EC in primary culture. Induction of PCD was evaluated successively by three independent criteria: (1) measurements of DNA fragmentation, (2) translocation of phosphatidylserine to the external leaflet of the plasma membrane, and (3) caspase-3 activation. Our results support the notion of an odorant-induced PCD in olfactory EC. This odorant-induced PCD was prevented by LY83583, an odorant response inhibitor, suggesting that ORNs are the main epithelial cell population undergoing odorant-induced PCD. [Copyright &y& Elsevier]

Compartmentalization of β-tubulin isotypes within cells according to function was examined in gerbil olfactory and respiratory epithelia by using specific antibodies to four β-tubulin isotypes (βI, βII, βIII, and βIV). Isotype synthesis was cell-type-specific, but the localization of the isotypes was not compartmentalized. All four isotypes were found in the cilia, dendrites, somata, and axons of olfactory neurons. Only two isotypes (βI and βIV) were present in the cilia of nasal respiratory epithelial cells. The βIV isotype, thought to be an essential component of cilia, was present in olfactory neurons and respiratory epithelial cells, which are ciliated, but was not found in basal cells (the stem cells of olfactory sensory neurons, which have no cilia). Olfactory neurons therefore do not synthesize βIV-tubulin until they mature, when functioning cilia are also elaborated. The failure to observe compartmentalization of β-tubulin isotypes in olfactory neurons sheds new light on potential functions of the β-tubulin isotypes. [ABSTRACT FROM AUTHOR]