Olfaction Research Articles

Genome-wide association analysis of hypertension and epigenetic aging reveals shared genetic architecture and identifies novel risk loci

Hypertension is a disease associated with epigenetic aging. However, the pathogenic mechanism underlying this relationship remains unclear. We aimed to characterize the shared genetic architecture of hypertension and epigenetic aging, and identify novel risk loci. Leveraging genome-wide association studies (GWAS) summary statistics of hypertension (129,909 cases and 354,689 controls) and four epigenetic clocks (N = 34,710), we investigated genetic architectures and genetic overlap using bivariate casual mixture model and conditional/conjunctional false discovery rate methods. Functional gene-sets pathway analyses were performed by functional mapping and gene annotation (FUMA) protocol. Hypertension was polygenic with 2.8 K trait-influencing genetic variants. We observed cross-trait genetic enrichment and genetic overlap between hypertension and all four measures of epigenetic aging. Further, we identified 32 distinct genomic loci jointly associated with hypertension and epigenetic aging. Notably, rs1849209 was shared between hypertension and three epigenetic clocks (HannumAge, IEAA, and PhenoAge). The shared loci exhibited a combination of concordant and discordant allelic effects. Functional gene-set analyses revealed significant enrichment in biological pathways related to sensory perception of smell and nervous system processes. We observed genetic overlaps with mixed effect directions between hypertension and all four epigenetic aging measures, and identified 32 shared distinct loci with mixed effect directions, 25 of which were novel for hypertension. Shared genes enriched in biological pathways related to olfaction.

Development of a noninvasive olfactory stimulation fMRI system in marmosets

Olfactory dysfunction is associated with aging and the earliest stages of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases; it is thought to be an early biomarker of cognitive decline. In marmosets, a small non-human primate model used in brain research, olfactory pathway activity during olfactory stimulation has not been well studied because of the difficulty in clearly switching olfactory stimuli inside a narrow MRI. Here, we developed an olfactory-stimulated fMRI system using a small-aperture MRI machine. The olfactory presentation system consisted of two tubes, one for supply and one for suction of olfactory stimulants and a balloon valve. A balloon valve installed in the air supply tube controlled the presentation of the olfactory stimulant, which enabled sharp olfactory stimulation within MRI, such as 30 s of stimulation repeated five times at five-minute intervals. The olfactory stimulation system was validated in vivo and in a simulated system. fMRI analysis showed a rapid increase in signal values within 30 s of olfactory stimulation in eight regions related to the sense of smell. As these regions include those associated with Alzheimer’s and Parkinson’s diseases, olfactory stimulation fMRI may be useful in clarifying the relationship between olfactory dysfunction and dementia in non-human primates.

Identification of nonsense variants in the genomes of 15 Murciano-Granadina bucks and analysis of their segregation in parent-offspring trios

Nonsense variants can inactivate gene function by causing the synthesis of truncated proteins or by inducing nonsense mediated decay of messenger RNAs. The occurrence of such variants in the genomes of livestock species is modulated by multiple demographic and selective factors. Even though nonsense variants can have causal effects on embryo lethality, abortions, and disease, their genomic distribution and segregation in domestic goats have not been characterized in depth yet. In this work, we have sequenced the genomes of 15 Murciano-Granadina bucks with an average coverage of 32.92 × ± 1.45 × . Bioinformatic analysis revealed 947 nonsense variants consistently detected with SnpEff and Ensembl-VEP. These variants were especially abundant in the 3'end of the protein-coding regions. Genes related to olfactory perception, ATPase activity coupled to transmembrane movement of substances, defense to virus, hormonal response, and sensory perception of taste were particularly enriched in nonsense variants. Seventeen nonsense variants expected to have harmful effects on fitness were genotyped in parent-offspring trios. We observed that several nonsense variants predicted to be lethal based on mouse knockout data did not have such effect, a finding that could be explained by the existence of multiple mechanisms counteracting lethality. These findings demonstrate that predicting the effects of putative nonsense variants on fitness is extremely challenging. As a matter of fact, such a goal could only be achieved by generating a high quality telomere-to-telomere goat reference genome combined with carefully curated annotation and functional testing of promising candidate variants.

The validity of clinical guidelines and nasal endoscopy in the diagnosis of chronic rhinosinusitis—a prospective observational study

BackgroundChronic rhinosinusitis is a common disease entity seen by ENT surgeons as well as general practitioners all over the world. This study is aimed to evaluate and validate whether the clinical guideline symptoms (set by AAO-HNS 2015) alone and/or nasal endoscopic findings can predict the diagnosis of CRS, taking CT as the gold standard.MethodsA total of 118 patients with symptoms of chronic rhinosinusitis were taken. They were divided into two groups on the basis of whether they fulfilled the Guideline symptom criteria laid down by AAO-HNS in 2015 for diagnosing chronic rhinosinusitis. Each group underwent diagnostic nasal endoscopy (DNE), and patients with either purulence, edema in the middle meatus or ethmoid, and polyps in the nasal cavity or middle meatus were considered positive for DNE. A Lund-Mackay CT score of > 4 was considered diagnostic of CRS. Each group was analyzed separately. Sensitivity, specificity, and positive predictive value of guideline symptom with and without the addition of nasal endoscopy was recorded taking CT as the gold standard.ResultsNasal obstruction was the most common seen in all cases (100%) followed by headache in 45 (38.1%), facial pain in 32 (27.1%), anterior nasal discharge in 28 (23.7%), decreased sense of smell in 22 (18.6%), and posterior nasal discharge in 19 (16.1%). Two-thirds of patients (78, 66.1%) fulfilled the clinical guideline symptoms criteria, and one-third of patients (40, 33.9%) did not fulfill the clinical guideline symptoms criteria. A positive finding on DNE was found in 59.3% (n = 70) of patients. More than half of patients (62, 52.5%) had mild grade on endoscopic examination, while only 8 (6.8%) had moderate grade, and none had severe grade. Guideline symptoms have a high sensitivity (80%) but a low specificity (50.94%) in the diagnosis of CRS, with a fair level of agreement with CT diagnosis (Kappa = 0.32). DNE has a moderate sensitivity (72.31%) but a low specificity (56.60%) in the diagnosis of CRS, with a fair level of agreement with CT diagnosis (Kappa = 0.29). Sensitivity and specificity were 80.77% and 57.69% respectively when guideline symptoms and DNE findings are taken in series.ConclusionWe conclude that neither Guideline Symptom Criteria nor DNE is independently sufficient enough to have a high diagnostic accuracy for CRS. Comparing the diagnostic efficiency among various modalities, we report that in patients who meet guideline symptom criteria for CRS, the addition of nasal endoscopy turned out to be a cost-effective diagnostic approach and improves the diagnostic accuracy of DNE for CRS reasonably, hence should be emphasized as a diagnostic tool in the evaluation of patients for CRS.

Understanding Olfactory Perception and its Significance in The Exploration of Sensescape Scenarios in Asian Cities

Researchers and designers have begun to devote more time and energy to studying urban escape scenarios because they know how important it is to comprehend the complex ways in which people perceive and interact with the built environment. Olfaction, the sense of scent, is an important part of this multimodal experience since it greatly influences how perceive and engage with the environment. The importance of smell is magnified in Asian urban settings since these places frequently offer a varied and varied sensory landscape, marked by a multitude of environmental, cultural, and gastronomic influences. Architects, urban planners, and legislators may develop more inclusive and responsive natural settings that cater to the multimodal demands of various people by understanding the function of olfactory perception in constructing the sensescape in these cities.

Distinct olfactory mucosal macrophage populations mediate neuronal maintenance and pathogen defense

The olfactory mucosa is important for both the sense of smell and as a mucosal immune barrier to the upper airway and brain. However, little is known about how the immune system mediates the conflicting goals of neuronal maintenance and inflammation in this tissue. A number of immune cell populations reside within the olfactory mucosa and yet we have little understanding of how these resident olfactory immune cells functionally interact with the chemosensory environment. Identifying these interactions will allow therapeutic manipulations that treat disorders such as post-viral olfactory dysfunction. Macrophages are the most prevalent immune cell type in the uninflamed olfactory mucosa and here, we identify two distinct tissue macrophage populations in murine olfactory mucosa. P2ry12hi macrophages are transcriptionally specialized for neuron interactions, closely associated with olfactory neuron cell bodies, long-term tissue residents, and functionally specialized to phagocytose cells and debris, including olfactory neurons. Conversely, MHC Class IIhi macrophages are transcriptionally dedicated to cytokine production and antigen presentation, localized primarily within the olfactory lamina propria, more rapidly replaced by blood monocytes, and rapidly produce chemokines in response to viral infection. We further show that these macrophage signatures are present in human olfactory biopsies, and P2ry12-like olfactory macrophages are reduced in patients with long-term smell loss following COVID-19. Together, these data show that two olfactory macrophage populations regulate neurons and initiate the immune response, contributing to our understanding of both olfactory immunity and tissue-resident macrophage biology.

Identification and characterization of olfactory gene families in Macrobrachium rosenbergii based on full-length transcripts and genome sequences

The olfactory gene families include odorant binding proteins (OBPs), chemosensory proteins (CSPs), olfactory receptors (ORs), ionotropic receptors (IRs) and gustatory receptors (GRs). To investigate the molecular function of olfactory perception in Macrobrachium rosenbergii, we integrated the full-length transcripts and whole-genome sequences to identify the olfactory gene families. In this study, a total of 38,955 full-length transcripts with an N50 length of 3383 bp were obtained through PacBio SMRT sequencing. Through the annotation of full-length transcripts and whole-genome sequences, several olfactory gene families were identified, including 18 MrORs, 16 MrIRs, 151 MrIGluRs (ionotropic glutamate receptors), 2 MrVIGluRs (variant ionotropic glutamate receptors) and 3 MrCRs (chemosensory receptors). Notably, the CRs were first identified in prawns and shrimps. Additionally, the olfactory gene families in M. nipponense were identified, comprising 4 MnORs, 21 MnIRs, 79 MnIGluRs, 5 MnVIGluRs, 1 MnGR and 1 MnOBP, using the available whole-genome sequences. Meanwhile, the external morphology of the chemical sensory organs of M. rosenbergii was explored, and the presence of plumose setae (PS), hard thorn setae (HTS), bamboo shoot setae (BSS), soft thorn setae (STS) and aesthetascs (AE) on the antennules, HTS and BSS on the second antennae, and PS on the pereiopods were observed by scanning electron microscope. This study provides valuable insights for future functional studies into the olfactory perception of crustaceans and establishes a theoretical basis for molecular design breeding in M. rosenbergii.

Predicting multiple taste sensations with a multiobjective machine learning method

Taste perception plays a pivotal role in guiding nutrient intake and aiding in the avoidance of potentially harmful substances through five basic tastes - sweet, bitter, umami, salty, and sour. Taste perception originates from molecular interactions in the oral cavity between taste receptors and chemical tastants. Hence, the recognition of taste receptors and the subsequent perception of taste heavily rely on the physicochemical properties of food ingredients. In recent years, several advances have been made towards the development of machine learning-based algorithms to classify chemical compounds’ tastes using their molecular structures. Despite the great efforts, there remains significant room for improvement in developing multi-class models to predict the entire spectrum of basic tastes. Here, we present a multi-class predictor aimed at distinguishing bitter, sweet, and umami, from other taste sensations. The development of a multi-class taste predictor paves the way for a comprehensive understanding of the chemical attributes associated with each fundamental taste. It also opens the potential for integration into the evolving realm of multi-sensory perception, which encompasses visual, tactile, and olfactory sensations to holistically characterize flavour perception. This concept holds promise for introducing innovative methodologies in the rational design of foods, including pre-determining specific tastes and engineering complementary diets to augment traditional pharmacological treatments.

Reinforced colour preference of parasitoid wasps in the presence of floral scent: a case study of a cross-modal effect

We examined the possibility of a cross-modal effect in naïve Cotesia vestalis, a parasitoid wasp of diamondback moth larvae, by using artificial flower models of four colours (blue, green, yellow, and red) in the absence or presence of floral scent collected from Brassica rapa inflorescences. In a four-choice test, regardless of the floral scent, non-starved female wasps visited green and yellow models significantly more often than blue and red ones, although no significant difference was observed between visits to the green and yellow models. They seldom visited blue and red models. When starved, the wasps became even more particular, visiting yellow significantly more frequently than green models, irrespective of the presence of the floral scent, indicating that they preferred to use yellow visual cues in their food search. Furthermore, a factorial analysis of variance revealed a significant effect of the interaction between model colour and floral scent on the wasps’ visits to flower models. The floral scent induced starved and non-starved wasps to visit yellow and green models about twice as often as without the scent. A cross-modal effect of olfactory perception on the use of chromatic information by wasps may allow them to search efficiently for food sources.

Identification and Functional Analysis of Odorant Binding Proteins in Apriona germari (Hope).

Apriona germari (Hope) presents a significant threat as a dangerous wood-boring pest, inflicting substantial harm to forest trees. Investigating the olfactory sensory system of A. germari holds substantial theoretical promise for developing eco-friendly control strategies. To date, however, the olfactory perception mechanism in A. germari remains largely unknown. Therefore, we performed transcriptome sequencing of A. germari across four distinct body parts: antennae, foreleg tarsal segments, mouthparts (maxillary and labial palps), and abdomen terminals, pinpointing the odorant binding protein (OBP) genes and analyzing their expression. We found eight AgerOBPs (5, 19, 23, 25, 29, 59, 63, 70) highly expressed in the antennae. In our competitive binding experiments, AgerOBP23 showed strong binding abilities to the pheromone component fuscumol acetate, eight plant volatiles (farnesol, cis-3-hexenal, nerolidol, myristol acetate, cis-3-hexenyl benzoate, (-)-α-cedrene, 3-ethylacetophenone, and decane), and four insecticides (chlorpyrifos, phoxim, indoxacarb, and cypermethrin). However, AgerOBP29 and AgerOBP63 did not show prominent binding activities to these tested chemicals. Through homology modeling and molecular docking, we identified the key amino acid sites involved in the binding process of AgerOBP23 to these ligands, which shed light on the molecular interactions underlying its binding specificity. Our study suggests that AgerOBP23 may serve as a potential target for future investigations of AgerOBP ligand binding. This approach is consistent with the reverse chemical ecology principle, establishing the groundwork for future studies focusing on attractant or repellent development by exploring further the molecular interactions between OBP and various compounds.

Sexual size dimorphism in mammals is associated with changes in the size of gene families related to brain development

In mammals, sexual size dimorphism often reflects the intensity of sexual selection, yet its connection to genomic evolution remains unexplored. Gene family size evolution can reflect shifts in the relative importance of different molecular functions. Here, we investigate the associate between brain development gene repertoire to sexual size dimorphism using 124 mammalian species. We reveal significant changes in gene family size associations with sexual size dimorphism. High levels of dimorphism correlate with an expansion of gene families enriched in olfactory sensory perception and a contraction of gene families associated with brain development functions, many of which exhibited particularly high expression in the human adult brain. These findings suggest a relationship between intense sexual selection and alterations in gene family size. These insights illustrate the complex interplay between sexual dimorphism, gene family size evolution, and their roles in mammalian brain development and function, offering a valuable understanding of mammalian genome evolution.

Head and neck complications of cancer therapies: taste and smell.

Sensory deficits affect awareness of the environment and information processing, leading to dysfunction that may have significant consequences. Deterioration of taste and/or smell sensation has been linked to impaired nutritional intake, and overall decreased quality of life (QoL). Recent data suggest that loss of these senses is also associated with cognitive decline and worse overall cancer treatment prognosis. Cancer therapies have commonly been associated with sensory deterioration. We review these associations with taste and smell in light of new findings and discuss potential prophylactic and therapeutic modalities for taste and smell function.

Olfactory and Gustatory Perception among Plant-Based vs. Omnivorous Dieters: A Systematic Review and Meta-Analysis

Driven by heightened awareness of environmental sustainability, personal health, and animal welfare, there has been a rapid surge in adoption of plant-based diets (PBDs) by global consumers. Despite the important implications of potential links between PBDs and chemosensory (e.g., olfactory and gustatory) perception, the empirical evidence has yet to be comprehensively reviewed. This systematic review aims to synthesise existing data comparing olfactory and gustatory perceptions among individuals following plant-based (including vegan, vegetarian, and flexitarian) and omnivorous diets. Seven databases produced 1038 publications for screening against the pre-registered criteria. Eleven studies were included in this review, with three focusing on olfaction and eight on gustation. Of these, three gustatory studies provided sufficient data for meta-analysis, revealing little difference between plant-based and omnivore dieters on an overall level. The PBD group exhibited a significantly lower threshold (i.e., higher sensitivity) to sweetness compared to the omnivore group (ES = −0.336, 95% CI between −0.630 and −0.042, p < 0.05). Additionally, olfactory studies indicated that PBD followers perceived meat-related odours to be less pleasant compared to omnivores. Overall, this review points to a sensory–diet relationship, highlighting the potential role of sensory perception in sustainable plant-based dietary behaviours. The findings also encourage food manufacturers to consider potential chemosensory alterations among plant-based consumers.

Behavioral adjustment of C. elegans to mechanosensory loss requires intact mechanosensory neurons.

Sensory neurons specialize in detecting and signaling the presence of diverse environmental stimuli. Neuronal injury or disease may undermine such signaling, diminishing the availability of crucial information. Can animals distinguish between a stimulus not being present and the inability to sense that stimulus in the first place? To address this question, we studied Caenorhabditis elegans nematode worms that lack gentle body touch sensation due to genetic mechanoreceptor dysfunction. We previously showed that worms can compensate for the loss of touch by enhancing their sense of smell, via an FLP-20 neuropeptide pathway. Here, we find that touch-deficient worms exhibit, in addition to sensory compensation, also cautious-like behavior, as if preemptively avoiding potential undetectable hazards. Intriguingly, these behavioral adjustments are abolished when the touch neurons are removed, suggesting that touch neurons are required for signaling the unavailability of touch information, in addition to their conventional role of signaling touch stimulation. Furthermore, we found that the ASE taste neurons, which similarly to the touch neurons, express the FLP-20 neuropeptide, exhibit altered FLP-20 expression levels in a touch-dependent manner, thus cooperating with the touch circuit. These results imply a novel form of neuronal signaling that enables C. elegans to distinguish between lack of touch stimulation and loss of touch sensation, producing adaptive behavioral adjustments that could overcome the inability to detect potential threats.

A new surgical technique to increase airflow in the olfactory cleft: superior turbinate lateralization procedure.

The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established. We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function. ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group. The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.

A deep position-encoding model for predicting olfactory perception from molecular structures and electrostatics

Predicting olfactory perceptions from odorant molecules is challenging due to the complex and potentially discontinuous nature of the perceptual space for smells. In this study, we introduce a deep learning model, Mol-PECO (Molecular Representation by Positional Encoding of Coulomb Matrix), designed to predict olfactory perceptions based on molecular structures and electrostatics. Mol-PECO learns the efficient embedding of molecules by utilizing the Coulomb matrix, which encodes atomic coordinates and charges, as an alternative of the adjacency matrix and its Laplacian eigenfunctions as positional encoding of atoms. With a comprehensive dataset of odor molecules and descriptors, Mol-PECO outperforms traditional machine learning methods using molecular fingerprints and graph neural networks based on adjacency matrices. The learned embeddings by Mol-PECO effectively capture the odor space, enabling global clustering of descriptors and local retrieval of similar odorants. This work contributes to a deeper understanding of the olfactory sense and its mechanisms.

Smell perception in virtual spacecraft? A ground‐based approach to sensory data collection

SummaryThe study explored context‐driven food odour perception with links to chemical profiling of flavour compounds. Participants rated the intensity of three food odours (vanilla, almond, lemon) in a Neutral context and VR simulation of the International Space Station. The study involved 54 adults aged 18–39 years with no history of motion sickness and/or vertigo. The VR context demonstrated significantly higher intensity ratings for vanilla (P = 0.009) and almond (P < 0.001) odours, compared to the Neutral context. Clustering based on perceived intensity identified that those less sensitive to the odours perceived significantly stronger almond odour in VR (P = 0.011). Gas chromatography–mass spectrometry analysis linked these findings to benzaldehyde, a common compound in both vanilla and almond odours. Therefore, a VR space context may impact odour perception, subject to their volatile composition and individual sensitivity. This underscores VR's potential as a ground‐based analogue for future sensory research, translating across similar settings beyond the space context.

Multisensory nature exposure in the workplace: Exploring the restorative benefits of smell experiences

Previous research has extensively documented several benefits of interacting with nature. Biophilic design applications aimed at connecting the built environment back to nature have been shown to improve employee health, well-being, and productivity at workplaces. However, most research regarding restorative environments has prioritized the visual qualities of nature experiences, neglecting other sensory modalities. The significance of the sense of smell in the restoration process has been largely ignored. This research investigates the combined effects of multi-domain nature experiences within workplace contexts. Specifically, the restorative benefits of combined multisensory elements, including visual, olfactory, and auditory, and the relative contributions of each sensory cue to the restoration process were examined. A pretest-posttest experimental approach was employed to compare the restorative outcomes of workplaces under two conditions, one lacking natural elements vs another offering multi-domain experiences of nature. Thirty-two participants engaged in a multisensory virtual reality simulation replicating the environmental conditions of an actual workplace in Sydney, Australia. The results revealed that the multisensory biophilic workplace significantly improved cognitive performance, reduced stress levels, and enhanced mood states compared to the non-biophilic one. There was a statistically significant association between the sense of smell and restorative benefits. Although visual elements emerged as the primary means of creating restorative workplace environments, our results suggest that the sense of smell plays a significant role in the restoration process. This paper provides empirical evidence on the paramount importance of olfactory cues in nature-based experiences, contributing to the knowledge within the realms of biophilia and architectural discourse.

Tropospheric ozone effect on olfactory perception and olfactory bulb dopaminergic interneuron excitability

Ozone (O3) forms in the Earth’s atmosphere, both naturally and by reactions of man-made air pollutants. Deleterious effects of O3 have been found in the respiratory system. Here, we examine whether O3 alters olfactory behavior and cellular properties in the olfactory system. For this purpose, mice were exposed to O3 at a concentration found in highly polluted city air [0.8 ppm], and the behavior elicited by social and non-social odors in habituation/dishabituation tests was assessed. In addition, the electrical responses of dopaminergic olfactory bulb (OB) neurons were also evaluated. O3 differentially compromises olfactory perception to odors: it reduces responses to social and non-social odors in Swiss Webster mice, while this effect was observed in C57BL/6 J mice only for some non-social odors. Additionally, O3 reduced the rate of spontaneous spike firing in periglomerular dopaminergic cells (PG-DA) of the OB. Because this effect could reflect changes in excitability and/or synaptic inputs, the ability of O3 to alter PG-DA spontaneous activity was also tested together with cell membrane resistance, membrane potential, rheobase and chronaxie. Taken together, our data suggest the ability of O3 to affect olfactory perception.

Sensory input from osphradium is involved in fluoride detection that alters feeding and memory phenotype in Lymnaea stagnalis

Fluoride (F-) exposure in organisms remains a significant concern due to its widespread presence and potential health implications. Investigating its detection and subsequent effects on behaviour in aquatic organisms like Lymnaea stagnalis provides valuable insights. Our study focused on elucidating the sensory pathways involved in F- detection and its impact on feeding and memory formation. We explored two potential detection mechanisms: direct flow across the integument onto neurons; and sensory input to the central nervous system (CNS) via the osphradium-osphradial ganglion-osphradial nerve pathway (snails use this system for olfactory sensation of multiple compounds). Injection of F- into snails did not alter feeding behaviour or central neuronal activity, suggesting that internalization might not be the primary detection mode. In contrast, severing the osphradial nerve abolished F-'s suppressive effects on feeding and memory formation, implicating the osphradial pathway in F- sensing and behavioural changes. This finding supports the idea that osphradial nerve signaling mediates the behavioural effects of F-. Our study underscores the importance of sensory pathways in F- detection and behavioural modulation in L. stagnalis. Understanding these mechanisms could provide critical insights into how organisms respond to and adapt to environmental chemical stressors like F-.