Olfactory System Research Articles

Elimination of olfactory sensory neurons by zinc sulfate inoculation prevents SARS-CoV-2 infection of the brain in K18-hACE2 transgenic mice.

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain.

Possible Mechanisms of the Influence of Oxytocin and Vazopressin on Perception and Memory of Odors and on Social Behavior

A possible mechanism is proposed for the influence of oxytocin and vasopressin on the functioning of the neural network in the CNS, in which olfactory information is processed and stored, and which plays an important role in social behavior. The effect of these neuropeptides on postsynaptic receptors associated with Gq/11 proteins contributes to the induction of LTP of the efficacy of excitatory synaptic inputs to the main projection cells and to inhibitory interneurons in the prefrontal cortex, hippocampus, piriform cortex, anterior olfactory nucleus, olfactory bulb and nucleus accumbens, including the olfactory tubercle. As a result of disynaptic inhibition in each of the structures, the signal-to-noise ratio is improved and the transmission of strong signals through projection neurons to their target cells is facilitated. Due to the fact, that oxytocin promotes the release of dopamine by the neurons of the ventral tegmental area, the conditions for processing and memorizing olfactory information in the interconnected olfactory and hippocampal neural networks, including cortical and subcortical structures, are improved, and attention is also included in this processing. Long-term modification of the effectiveness of interneuronal connections in these networks under the influence of oxytocin and dopamine contributes to the formation and stabilization of contrasting neuronal representation of odors formed in cortical areas. Orientation of attention increases the significance of socially important olfactory stimuli and improves the conditions for the functioning of the reinforcement system necessary for adequate social behavior. Taking into account the known data on the correlation between social behavior and the density of oxytocin and vasopressin receptors on neurons of different structures, understanding the mechanisms of the influence of these neuropeptides on the functioning of the olfactory system can be useful for finding ways to correct behavior if necessary.

DDEL-03. INTRANASAL DELIVERY OF PDGFRA-TARGETED NANOTHERAPEUTICS FOR THE TREATMENT OF PEDIATRIC HIGH-GRADE GLIOMA

Abstract Pediatric high-grade glioma (pHGG) is the most common cause of cancer-related death in children, of which the most malignant and devastating tumors include diffuse midline glioma (DMG). Its anatomical location in the brainstem, infiltrative nature, and blood-brain barrier (BBB) limit surgical resection and the distribution of systemically administered drugs. Intranasal delivery (IND) is a noninvasive method that bypasses the BBB, by leveraging the unique anatomic connections of the olfactory and trigeminal nerve pathways with the nasal cavity. We previously demonstrated the efficacy of IND of nanoliposomal (LS) formulation of the active metabolite of the DNA topoisomerase I inhibitor, irinotecan, LS-SN-38, in orthotopic human brainstem xenograft models. The specificity of liposomes can be enhanced by using immunoliposome (iLS) formulation, which are coated with antibodies specific to the tumor cells leading to targeted drug delivery and reduced toxicity to normal cells. Platelet-derived growth factor receptor alpha (PDGFRA) plays a role in DMG oncogenesis and is expressed in as much as 70% of DMG by immunohistochemistry. In this study, we evaluated the effect of anti-PDGFRA monoclonal antibody-conjugated immunoliposome encapsulated SN-38 (PDGFRA-iLS-SN-38) in pHGG cell lines. PDGFRA signals were assessed in pHGG cells using western blotting. Cells were treated with rhodamine (Rho)-labeled PDGFRA-iLS and cellular uptake was confirmed with a fluorescent microscope. PDGFRA-iLS-SN38 had the additive effect on the LS-SN-38 in DIPG007 cells (PDGFRA positive), but not in SF8628 cells (PDGFRA negative) in vitro. We treated mice bearing human DMG xenografts with IND of PDGFRA-iLS-SN38. Tumor growth and response to therapy are quantitatively measured by bioluminescence imaging, and efficacy is assessed by survival analysis. Results of survival analysis will be reported at the meeting. PDGFRA-targeted nanotherapeutics represented a specific effect on glioma cells expressing PDGFRA, providing a promising therapeutic approach for targeting pHGG.

Network transformation-based analysis of biochemical systems.

A dynamical system obtains a wide variety of kinetic realizations, which is advantageous for the analysis of biochemical systems. A reaction network, derived from a dynamical system, may or may not possess some properties needed for a thorough analysis. We improve and extend the work of Johnston and Hong et al. on network translations to network transformations, where the network is modified while preserving the dynamical system. These transformations can shrink, extend, or retain the stoichiometric subspace. Here, we show that a positive dependent network can be translated to a weakly reversible network. Using the kinetic realizations of (1) calcium signaling in the olfactory system and (2) metabolic insulin signaling, we demonstrate the benefits of transformed systems with positive deficiency for analyzing biochemical systems. Furthermore, we present an algorithm for a network transformation of a weakly reversible non-complex factorizable kinetic (NFK) system to a weakly reversible complex factorizable kinetic (CFK) system, thereby enhancing the Subspace Coincidence Theorem for NFK systems of Nazareno et al. Finally, using the transformed kinetic realization of monolignol biosynthesis in Populus xylem, we study the structural and kinetic properties of transformed systems, including the invariance of concordance and variation of injectivity and mono-/multi-stationarity under network transformation.

Female contact sex pheromone recognition in the German cockroach (Blattella germanica) is mediated by two male antennae-enriched sensory neuron membrane proteins.

The German cockroach Blattella germanica is a notorious urban health pest that has developed resistance to multiple pesticides. Thus, novel non-lethal pest control agents are urgently needed. Olfaction interference via disruption of sex pheromone recognition-related genes offers a promising approach. The German cockroach has a unique courtship behavior in which female adults emit contact sex pheromones (CSPs) in response to antennal touching, which subsequently triggers distinctive male sex behavioral responses. Due to the limited volatility of CSPs, the molecular mechanisms underlying their recognition and the specific olfactory pathways activated remain poorly defined. Although the odorant receptor coreceptor (Orco) is critical for most insect olfaction, sensory neuron membrane proteins (SNMPs), in particular SNMP1, also play crucial roles in sex pheromone recognition in moths and flies. While multiple SNMP1 homologs have been identified in multiple insect species, they have yet to be fully functionally characterized in cockroaches. In this study, RNA-interference (RNAi)-mediated knockdown of BgerOrco reduced both the electrophysiology responses and courtship behaviors of males, indicating CSP perception proceeds via an olfaction pathway. Similar RNAi knockdown of BgerSNMP1e and BgerSNMP1d, which are predominantly expressed in male antennae, revealed critical roles in perceiving the major component of the Blattella germanica CSP blend. Unlike BgerSNMP1e, BgerSNMP1d was also found to function in the perception of the minor CSP component. Molecular docking analyses revealed no differences in the binding affinities of BgerSNMP1d for the major and minor CSP components, whereas the binding affinities of BgerSNMP1e displayed clear selectivity for the major component. Our results show that the olfactory pathway is critical for CSP recognition and that two male-enriched SNMP genes, BgerSNMP1e and BgerSNMP1d, are crucial factors mediating the male response to CSP stimulation in German cockroaches. This study lays a foundation for studying the mechanisms of CSP recognition and provides novel molecular targets with potential to be exploited as disruptors of courtship behavior. © 2024 Society of Chemical Industry.

Direct piriform-to-auditory cortical projections shape auditory-olfactory integration.

In a real-world environment, the brain must integrate information from multiple sensory modalities, including the auditory and olfactory systems. However, little is known about the neuronal circuits governing how odors influence and modulate sound processing. Here, we investigated the mechanisms underlying auditory-olfactory integration using anatomical, electrophysiological, and optogenetic approaches, focusing on the auditory cortex as a key locus for cross-modal integration. First, retrograde and anterograde viral tracing strategies revealed a direct projection from the piriform cortex to the auditory cortex. Next, using in vivo electrophysiological recordings of neuronal activity in the auditory cortex of awake male or female mice, we found that odors modulate auditory cortical responses to sound. Finally, we used in vivo optogenetic manipulations during electrophysiology to demonstrate that olfactory modulation in auditory cortex, specifically, odor-driven enhancement of sound responses, depends on direct input from the piriform cortex. Together, our results identify a novel role of piriform-to-auditory cortical circuitry in shaping olfactory modulation in the auditory cortex, shedding new light on the neuronal mechanisms underlying auditory-olfactory integration.Significance Statement All living organisms exist within multisensory environments, yet there is a lack in our understanding of how the brain integrates multisensory information. This work highlights a direct piriform-to-auditory cortical circuit governing auditory-olfactory integration. Our results shed new light on a relatively understudied area of multisensory research, promising a more robust understanding of how animals and humans perceive and interact within complex environments.

Late olfactory bulb involvement in COVID19.

Transient or persistent hypo-anosmia is common in SARS‑CoV‑2 infection but olfactory pathway late-term morphometric changes are still under investigation. We evaluated late olfactory bulb (OB) imaging changes and their correlates with the olfactory function in otherwise neurologically asymptomatic COVID-19 patients. Eighty-three subjects (mean-age 43±14 years; 54 females; time-interval infection/MRI: 129±68 days) affected by asymptomatic to mild COVID19 in 2020 and 25 healthy controls (mean-age 40±13 years; 9 females) underwent 3T-MRI and olfactory function evaluation through anamnestic questionnaire and Sniffin' Sticks. Exclusion criteria were intensive care treatment or neurological involvement other than olfaction. Maximal OB area was measured blindly on high-resolution coronal T2w images by two observers. Patients were subdivided into: i) persistently hypo/anosmic, ii) recovered normosmic and iii) never complaining smell dysfunction with proven normal olfactory function. No significant differences were observed among patients' subgroups (p=0.76). Intra-observer and inter-observer reliability were high.(r=0.96 and 0.86). Former COVID19 patients had decreased mean maximal OB area than controls (6.52±1.11mm2 vs 7.26±1.17mm2, p=0.008) even when considering persistently hypo-anosmic (6.46±0.90, p=0.006) or normosmic patients at MRI (6.57±1.25, p=0.04). SARS-CoV-2 infection is associated with mid/late-term morphological changes on the olfactory bulbs, regardless of presence or persistence of olfactory dysfunction. The long-term consequences on olfactory aging need to be further investigated including possible links with neurodegenerative disorders.

Olfactory Development and Dysfunction - Involvement of Microglia.

Olfactory deficits are increasingly recognized in a variety of neurological, neurodevelopmental, psychiatric and viral diseases. While the pathology underlying olfactory loss is likely to differ across diseases, one shared feature may be an immune response mediated by microglia. Microglia orchestrate the brain's response to environmental insults and maintain neurodevelopmental homeostasis. Here, we explore the potential involvement of microglia in olfactory development and loss in disease. The effects of microglia-mediated immune response during development may be of special relevance to the olfactory system, which is unique in both its vulnerability to environmental insults as well as its extended period of neurogenesis and neuronal migration.

Cannabinoid regulation of sex-dependent murine odorant-stimulated salivation

Salivation is easily taken for granted, but without normal salivation, simple essential tasks such as chewing and swallowing become difficult, with consequences for quality of life, nutrition and oral health. Many important drug classes cause dry mouth as a side effect, contributing substantially to patient non-compliance. Available treatments are mostly palliative. Cannabis user complaints of dry mouth prompted a study that showed that basal salivation is likely regulated by cannabinoid CB1 receptors on neurons that innervate the submandibular gland. But what about stimulated salivation? The adjoining parotid gland releases saliva in response to olfactory or other cues and contributes a large portion of the net salivation in humans. We investigated cannabinoid regulation of stimulated salivation using functional and protein-expression studies in mice. In developing a model of stimulated salivary responses to food-related odorants in mice, we noted sex-dependent responses to food-related cues. Only male mice learned to salivate in response to the odor of peanut butter while only female mice responded to a chocolate hazelnut spread. Both males and females responded to sugar or marmite. Testing peanut butter, we found that the cannabinoid receptor agonist CP55940 (0.5 mg/kg, IP) lowered baseline salivation, as shown previously, but also prevented the odorant-induced increase in salivation. CB1 receptors are expressed in axons innervating the parotid gland, paralleling our findings in the submandibular gland. Notably, we also found that CB1 deletion impaired some responses (those to peanut butter and chocolate hazelnut spread) but not others (sugar or marmite). In mice, the CB1 antagonist SR141716 (4 mg/kg, IP) prevented a previously learned salivary response to peanut butter. We find that CB1 receptors are expressed in a subset of glomeruli in coronal sections of olfactory bulb that may serve as a site of action for scent-specific effects of CB1 receptors. We additionally observe CB1 expression in accessory olfactory bulb. In summary, we find a novel sex-dependence in responses to a subset of food-related odorant cues and that cannabinoid receptors regulate some of these responses. We propose that CB1 receptors act at the parotid gland to inhibit stimulated salivation but also in the olfactory system, where functional CB1 receptors are required for salivary responses to specific appetitive odors.

Wing–antenna interaction reduces odour fatigue in butterfly odour-tracking flight

Flying insects exhibit remarkable capabilities in coordinating their olfactory sensory system and flapping wings during odour plume-tracking flights. While observations have indicated that their flapping wing motion can ‘sniff’ up the incoming plumes for better odour sampling range, how flapping motion impacts the odour concentration field around the antennae is unknown. Here, we reconstruct the body and wing kinematics of a forwards-flying butterfly based on high-speed images. Using an in-house computational fluid dynamics solver, we simulate the unsteady flow field and odourant transport process by solving the Navier–Stokes and odourant advection-diffusion equations. Our results show that, during flapping flight, the interaction between wing leading-edge vortices and antenna vortices strengthens the circulation of antenna vortices by over two-fold compared with cases without flapping motion, leading to a significant increase in odour intensity fluctuation along the antennae. Specifically, the interaction between the wings and antennae amplifies odour intensity fluctuations on the antennae by up to 8.4 fold. This enhancement is critical in preventing odour fatigue during odour-tracking flights. Further analysis reveals that this interaction is influenced by the inter-antennal angle. Adjusting this angle allows insects to balance between resistance to odour fatigue and the breadth of odour sampling. Narrower inter-antennal angles enhance fatigue resistance, while wider angles extend the sampling range but reduce resistance. Additionally, our findings suggest that while the flexibility of the wings and the thorax's pitching motion in butterflies do influence odour fluctuation, their impact is relatively secondary to that of the wing–antenna interaction.

Olfactory Dysfunction and Limbic Hypoactivation in Temporal Lobe Epilepsy.

The epileptogenic network in temporal lobe epilepsy (TLE) contains structures of the primary and secondary olfactory cortex such as the piriform and entorhinal cortex, the amygdala, and the hippocampus. Olfactory auras and olfactory dysfunction are relevant symptoms of TLE. This study aims to characterize olfactory function in TLE using olfactory testing and olfactory functional magnetic resonance imaging (fMRI). We prospectively enrolled 20 individuals with unilateral TLE (age 45 ± 20 years [mean ± SD], 65% female, 90% right-handed) and 20 healthy individuals (age 33 ± 15 years [mean ± SD], 35% female, 90% right-handed). In the TLE group, the presumed seizure onset zone was left-sided in 75%; in 45% of the individuals with TLE limbic encephalitis was the presumed etiology; and 15% of the individuals with TLE reported olfactory auras. Olfactory function was assessed with a Screening Sniffin' Sticks Test (Burkhart, Wedel, Germany) during a pre-assessment. During a pre-testing, all individuals were asked to rate the intensity, valence, familiarity, and associated memory of five different odors (eugenol, vanillin, phenethyl alcohol, decanoic acid, valeric acid) and a control solution. During the fMRI experiment, all individuals repeatedly smelled eugenol (positively valenced odor), valeric acid (negatively valenced odor), and the control solution and were asked to rate odor intensity on a five-point Likert scale. We acquired functional EPI sequences and structural images (T1, T2, FLAIR). Compared to healthy individuals, individuals with TLE rated the presented odors as more neutral (two-sided Mann-Whitney U tests, FDR-p < 0.05) and less familiar (two-sided Mann-Whitney U tests, FDR-p < 0.05). fMRI data analysis revealed a reduced response contrast in secondary olfactory areas (e.g., hippocampus) connected to the limbic system when comparing eugenol and valeric acid in individuals with TLE when compared with healthy individuals. However, no lateralization effect was obtained when calculating a lateralization index by the number of activated voxels in the olfactory system (two-sided Mann-Whitney U test; U = 176.0; p = 0.525). TLE is characterized by olfactory dysfunction and associated with hypoactivation of secondary olfactory structures connected to the limbic system. These findings contribute to our understanding of the pathophysiology of TLE. This study was preregistered on OSF Registries (www.osf.io).

Novo plant-based mosquito repellent shows promise for exclusion of Aedes mosquitoes from "window" entry.

Mosquitoes threaten over half of the world's population through vectored diseases such as malaria, zika, yellow fever, dengue, and chikungunya. Mosquitoes have a highly developed olfactory system attuned to chemotaxis relating to host-seeking, mating, and oviposition behavior. In this study, we aimed to determine the spatial efficacy of 2 plant-based repellent blends (Blend3 and Blend4that had previously been found to successfully repel Aedes, Anopheles and Culex mosquitoes in wind tunnel assays)in excluding Aedes aegypti from the window entry. A new cage system was developed for parallel "no-choice" and "choice" olfactometric assays. In the no-choice trial, Blends 3 and 4, as well as commercial products (N, N-diethyl-3-methylbenzamide, p-menthane-3,8-diol [PMD], 3-(N-n-butyl-N-acetyl)-amino-propionic acid ethyl ester, and 2-(2-hydroxyethyl)-1-methylpropylstyrene 1-piperidine carboxylate), were adsorbed into filter papers of different sizes and placed in a window created between 2 attached bug dorms. Then, the number of mosquitoes entering the window was counted through a 6-min period. In choice olfactometric assays, Blends 3, 4, and PMD were adsorbed into filter paper and the number of mosquitoes moving away from Blend 3 and PMD were compared. No-choice assays showed that Blend3 (P < 0.001) and Blend4 (P = 0.0012) were more repellent than the best commercial product PMD. Additionally, while Blend 4 was significantly more repellent than Blend 3 (P = 0.012) in the choice assay, overall, these 2 blends show promise as new repellents for the spatial exclusion of Aedes aegypti from window entry alone or as part of a "push-pull'' strategy.

Rhythms in insect olfactory systems: underlying mechanisms and outstanding questions.

Olfaction is a critical sensory modality for invertebrates, and it mediates a wide range of behaviors and physiological processes. Like most living organisms, insects live in rhythmic environments: the succession of nights and days is accompanied by cyclic variations in light intensity and temperature, as well as in the availability of resources and the activity of predators. Responding to olfactory cues in the proper temporal context is thus highly adaptive and allows for the efficient allocation of energy resources. Given the agricultural or epidemiological importance of some insect species, understanding olfactory rhythms is critical for the development of effective control strategies. Although the vinegar fly Drosophila melanogaster has been a classical model for the study of olfaction and circadian rhythms, recent studies focusing on non-model species have expanded our understanding of insect olfactory rhythms. Additionally, recent evidence revealing receptor co-expression by sensory neurons has brought about an ongoing paradigm shift in our understanding of insect olfaction, making it timely to review the state of our knowledge on olfactory rhythms and identify critical future directions for the field. In this Review, we discuss the multiple biological scales at which insect olfactory rhythms are being analyzed, and identify outstanding questions.

Beyond anosmia: olfactory dysfunction as a common denominator in neurodegenerative and neurodevelopmental disorders.

Olfactory dysfunction has emerged as a hallmark feature shared among several neurological conditions, including both neurodevelopmental and neurodegenerative disorders. While diseases of both categories have been extensively studied for decades, their association with olfaction has only recently gained attention. Olfactory deficits often manifest already during prodromal stages of these diseases, yet it remains unclear whether common pathophysiological changes along olfactory pathways cause such impairments. Here we probe into the intricate relationship between olfactory dysfunction and neurodegenerative and neurodevelopmental disorders, shedding light on their commonalities and underlying mechanisms. We begin by providing a brief overview of the olfactory circuit and its connections to higher-associated brain areas. Additionally, we discuss olfactory deficits in these disorders, focusing on potential common mechanisms that may contribute to olfactory dysfunction across both types of disorders. We further debate whether olfactory deficits contribute to the disease propagation or are simply an epiphenomenon. We conclude by emphasizing the significance of olfactory function as a potential pre-clinical diagnostic tool to identify individuals with neurological disorders that offers the opportunity for preventive intervention before other symptoms manifest.

Engineered odorant receptors illuminate the basis of odour discrimination.

How the olfactory system detects and distinguishes odorants with diverse physicochemical properties and molecular configurations remains poorly understood. Vertebrate animals perceive odours through G protein-coupled odorant receptors (ORs)1. In humans, around 400 ORs enable the sense of smell. The OR family comprises two main classes: class I ORs are tuned to carboxylic acids whereas class II ORs, which represent most of the human repertoire, respond to a wide variety of odorants2. A fundamental challenge in understanding olfaction is the inability to visualize odorant binding to ORs. Here we uncover molecular properties of odorant-OR interactions by using engineered ORs crafted using a consensus protein design strategy3. Because such consensus ORs (consORs) are derived from the 17 major subfamilies of human ORs, they provide a template for modelling individual native ORs with high sequence and structural homology. The biochemical tractability of consORs enabled the determination of four cryogenic electron microscopy structures of distinct consORs with specific ligand recognition properties. The structure of a class I consOR, consOR51, showed high structural similarity to the native human receptor OR51E2 and generated a homology model of a related member of the human OR51 family with high predictive power. Structures of three class II consORs revealed distinct modes of odorant-binding and activation mechanisms between class I and class II ORs. Thus, the structures of consORs lay the groundwork for understanding molecular recognition of odorants by the OR superfamily.

A Drosophila-inspired intelligent olfactory biomimetic sensing system for gas recognition in complex environments

The olfactory sensory system of Drosophila has several advantages, including low power consumption, high rapidity and high accuracy. Here, we present a biomimetic intelligent olfactory sensing system based on the integration of an 18-channel microelectromechanical system (MEMS) sensor array (16 gas sensors, 1 humidity sensor and 1 temperature sensor), a complementary metal‒oxide‒semiconductor (CMOS) circuit and an olfactory lightweight machine-learning algorithm inspired by Drosophila. This system is an artificial version of the biological olfactory perception system with the capabilities of environmental sensing, multi-signal processing, and odor recognition. The olfactory data are processed and reconstructed by the combination of a shallow neural network and a residual neural network, with the aim to determine the noxious gas information in challenging environments such as high humidity scenarios and partially damaged sensor units. As a result, our electronic olfactory sensing system is capable of achieving comprehensive gas recognition by qualitatively identifying 7 types of gases with an accuracy of 98.5%, reducing the number of parameters and the difficulty of calculation, and quantitatively predicting each gas of 3–5 concentration gradients with an accuracy of 93.2%; thus, these results show superiority of our system in supporting alarm systems in emergency rescue scenarios.

Genomes of Microtus rodents highlight the importance of olfactory and immune systems in their fast radiation.

The characterization of genes and biological functions underlying functional diversification and the formation of species is a major goal of evolutionary biology. In this study, we investigated the fast radiation of Microtus voles, one of the most speciose group of mammals, which shows strong genetic divergence despite few readily observable morphological differences. We produced an annotated reference genome for the common vole, Microtus arvalis, and resequenced the genomes of 10 different species and evolutionary lineages spanning the Microtus speciation continuum. Our full genome sequences illustrate the recent and fast diversification of this group, and we identified genes in highly divergent genomic windows that have likely particular roles in their radiation. We found three biological functions enriched for highly divergent genes in most Microtus species and lineages: olfaction, immunity and metabolism. In particular, olfaction-related genes (mostly olfactory receptors and vomeronasal receptors) are fast evolving in all Microtus species indicating the exceptional importance of the olfactory system in the evolution of these rodents. Of note is e.g. the shared signature among vole species on Olfr1019 which has been associated with fear responses against predator odours in rodents. Our analyses provide a genome-wide basis for the further characterization of the ecological factors and processes of natural and sexual selection that have contributed to the fast radiation of Microtus voles.

Convergent olfactory circuits for courtship in Drosophila revealed by ds-Tango.

Animals exhibit sex-specific behaviors that are governed by sexually dimorphic circuits. One such behavior in male Drosophila melanogaster, courtship, is regulated by various sensory modalities, including olfaction. Here, we reveal how sexually dimorphic olfactory pathways in male flies converge at the third-order, onto lateral horn output neurons, to regulate courtship. To achieve this, we developed ds-Tango, a modified version of the monosynaptic tracing and manipulation tool trans-Tango. In ds-Tango, two distinct configurations of trans-Tango are positioned in series, thus providing selective genetic access not only to the monosynaptic partners of starter neurons but also to their disynaptic connections. Using ds-Tango, we identified a node of convergence for three sexually dimorphic olfactory pathways. Silencing this node results in deficits in sex recognition of potential partners. Our results identify lateral horn output neurons required for proper courtship behavior in male flies and establish ds-Tango as a tool for disynaptic circuit tracing.

Olfactory Dysfunction in Obesity and Type 2 Diabetes

The article analyzes literature data on the close relationship between energy balance and sense of smell. Olfaction is one of the main modalities of hedonic evaluation of food. Odor is one of the most important sensory signals predicting food quality and plays a key role in food selection and consumption. Appetite can be stimulated by various stimuli, but the leading role belongs to olfactory signals (tasty smells) and levels of hormones that signal hunger and satiety. Olfactory perception is subject to hormonal modulation. In this regard, special attention in the article is paid to the modulating function of insulin. Insulin, one of the main metabolic hormones that controls food intake, has an anorexigenic effect not only at the level of the hypothalamus, but also at the level of the olfactory pathway, especially strong in the olfactory bulb. It has a rate of insulin transport two to eight times higher than in other parts of the brain, and it contains the highest concentration of insulin and the highest density of insulin receptor kinase. Thus, insulin is not only able to penetrate to the site of olfactory information processing, but do so quickly. At the same time, insulin and its receptors are localized in the olfactory epithelium, namely in mature olfactory sensory neurons. Therefore, insulin affects the primary stage of perception of an odorous molecule – odor detection, which occurs at the level of the olfactory epithelium. The sense of smell is impaired up to its complete loss in obesity and type 2 diabetes, worsening the quality of life of such patients. The paper examines the effectiveness of intranasal insulin administration to restore olfactory function in metabolic disorders and other diseases.

Olfactory and gustatory chemical sensor systems in the African turquoise killifish: Insights from morphology.

Smell and taste are extensively studied in fish species as essential for finding food and selecting mates while avoiding toxic substances and predators. Depending on the evolutionary position and adaptation, a discrete variation in the morphology of these sense organs has been reported in numerous teleost species. Here, for the first time, we approach the phenotypic characterization of the olfactory epithelium and taste buds in the African turquoise killifish (Nothobranchius furzeri), a model organism known for its short lifespan and use in ageing research. Our observations indicate that the olfactory epithelium of N. furzeri is organized as a simple patch, lacking the complex folding into a rosette, with an average size of approximately 600µm in length, 300µm in width, and 70µm in thickness. Three main cytotypes, including olfactory receptor neurons (CalbindinD28K), supporting cells (β-tubulin IV), and basal cells (Ki67), were identified across the epithelium. Further, we determined the taste buds' distribution and quantification between anterior (skin, lips, oral cavity) and posterior (gills, pharynx, oesophagus) systems. We identified the key cytotypes by using immunohistochemical markers, i.e. CalbindinD28K, doublecortin, and neuropeptide Y (NPY) for gustatory receptor cells, glial fibrillary acidic protein (GFAP) for supporting cells, and Ki67, a marker of cellular proliferation for basal cells. Altogether, these results indicate that N. furzeri is a microsmatic species with unique taste and olfactory features and possesses a well-developed posterior taste system compared to the anterior. This study provides fundamental insights into the chemosensory biology of N. furzeri, facilitating future investigations into nutrient-sensing mechanisms and their roles in development, survival, and ageing.