Abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) - the causal agent in COVID-19 - affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

Abstract: Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Abstract: Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic However, the cellular mechanism behind the sudden loss of smell has not yet been investigated The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier In the present study, we explored the impact of SARS-CoV-2 infection on the olfactory system in golden Syrian hamsters We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE The OE was partially restored 14 days post infection Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria

Abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

Abstract: Background Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients. Methods Olfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). Patients with COVID-19 and abnormal olfaction were further evaluated using the smell identification test (SIT), sinus imaging, and nasoendoscopy. Selected patients received nasal biopsies. Systematic review was performed according to PRISMA guidelines. PubMed items from January 1, 2020 to April 23, 2020 were searched. Studies that reported clinical data on olfactory disturbances in COVID-19 patients were analyzed. Results We included 18 COVID-19 patients and 18 controls. Among COVID-19 patients, 12 of 18 (67%) reported olfactory symptoms and OD was confirmed in 6 patients by BTT and SIT. Olfactory dysfunction was the only symptom in 2 patients. Mean BTT score of patients was worse than controls (P = .004, difference in means = 1.8; 95% confidence interval, 0.6-2.9). Sinusitis and olfactory cleft obstruction were absent in most patients. Immunohistochemical analysis of nasal biopsy revealed the presence of infiltrative CD68+ macrophages harboring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in the stroma. Olfactory dysfunction persisted in 2 patients despite clinical recovery. Systematic review showed that the prevalence of olfactory disturbances in COVID-19 ranged from 5% to 98%. Most studies did not assess olfaction quantitatively. Conclusions Olfactory dysfunction is common in COVID-19 and may be the only symptom. Coronavirus disease 2019-related OD can be severe and prolonged. Mucosal infiltration by CD68+ macrophages expressing SARS-CoV-2 viral antigen may contribute to COVID-19-related OD.

Abstract: Animals rely on their chemosensory system to discriminate among a very large number of attractive or repulsive chemical cues in the environment, which is essential to respond with proper action. The olfactory sensory systems in insects share significant similarities with those of vertebrates, although they also exhibit dramatic differences, such as the molecular nature of the odorant receptors (ORs): insect ORs function as heteromeric ion channels with a common Orco subunit, unlike the G-protein-coupled olfactory receptors found in vertebrates. Remarkable progress has recently been made in understanding the evolution, development and function of insect odorant receptor neurons (ORNs). These studies have uncovered the diversity of olfactory sensory systems among insect species, including in eusocial insects that rely extensively on olfactory sensing of pheromones for social communication. However, further studies, notably functional analyses, are needed to improve our understanding of the origins of the Orco-OR system, the mechanisms of ORN fate determination, and the extraordinary diversity of behavioral responses to chemical cues.

Abstract: Insect intraspecific olfactory communication occurs in a complex sensory environment. Here we present recent results on how the olfactory system extracts specific information from a sensory background, and integrates it with complementary information to improve odor source localization. Recent advances on mechanisms of olfactory mixture processing, multi-modal integration, as well as plasticity of sensory processing are reviewed. Significant progress in the understanding of neural coding and molecular bases of olfaction reinforce our perception of the tremendous adaptability of insects to a changing environment. However several reports demonstrate that anthropogenic environmental perturbations interfere with insect olfactory communication and might as a consequence significantly alter the functioning of ecosystems and agroecosystems.

Abstract: Insects thrive in diverse ecological niches in large part because of their highly sophisticated olfactory systems. Over the last two decades, a major focus in the study of insect olfaction has been on the role of olfactory receptors in mediating neuronal responses to environmental chemicals. In vivo, these receptors operate in specialized structures, called sensilla, which comprise neurons and non-neuronal support cells, extracellular lymph fluid and a precisely shaped cuticle. While sensilla are inherent to odour sensing in insects, we are only just beginning to understand their construction and function. Here, we review recent work that illuminates how odour-evoked neuronal activity is impacted by sensillar morphology, lymph fluid biochemistry, accessory signalling molecules in neurons and the physiological crosstalk between sensillar cells. These advances reveal multi-layered molecular and cellular mechanisms that determine the selectivity, sensitivity and dynamic modulation of odour-evoked responses in insects.

Abstract: Olfactory and metabolic dysfunctions are intertwined phenomena associated with obesity and neurodegenerative diseases; yet how mechanistically olfaction regulates metabolic homeostasis remains unclear. Specificity of olfactory perception integrates diverse environmental odors and olfactory neurons expressing different receptors. Here, we report that specific but not all olfactory neurons actively regulate fat metabolism without affecting eating behaviors in Caenorhabditis elegans, and identified specific odors that reduce fat mobilization via inhibiting these neurons. Optogenetic activation or inhibition of the responsible olfactory neural circuit promotes the loss or gain of fat storage, respectively. Furthermore, we discovered that FLP-1 neuropeptide released from this olfactory neural circuit signals through peripheral NPR-4/neuropeptide receptor, SGK-1/serum- and glucocorticoid-inducible kinase, and specific isoforms of DAF-16/FOXO transcription factor to regulate fat storage. Our work reveals molecular mechanisms underlying olfactory regulation of fat metabolism, and suggests the association between olfactory perception specificity of each individual and his/her susceptibility to the development of obesity. Olfaction is a key sensory modality with high diversity and olfactory defects has been associated with metabolic and neurodegenerative disorders. Here, the authors discovered that specific olfactory inputs actively regulate lipid metabolism in a dynamic and reversible manner.

Abstract: Background Endoscopic endonasal approaches pose the potential risk of olfactory loss. Loss of olfaction and potentially taste can be permanent and greatly affect patients' quality of life. Treatments for olfactory loss have had limited success. Omega-3 supplementation may be a therapeutic option with its effect on wound healing and nerve regeneration. Objective To evaluate the impact on olfaction in patients treated with omega-3 supplementation following endoscopic skull base tumor resection. Methods In this multi-institutional, prospective, randomized controlled trial, 110 patients with sellar or parasellar tumors undergoing endoscopic resection were randomized to nasal saline irrigations or nasal saline irrigations plus omega-3 supplementation. The University of Pennsylvania Smell Identification Test (UPSIT) was administered preoperatively and at 6 wk, 3 mo, and 6 mo postoperatively. Results Eighty-seven patients completed all 6 mo of follow-up (41 control arm, 46 omega-3 arm). At 6 wk postoperatively, 25% of patients in both groups experienced a clinically significant loss in olfaction. At 3 and 6 mo, patients receiving omega-3 demonstrated significantly less persistent olfactory loss compared to patients without supplementation (P = .02 and P = .01, respectively). After controlling for multiple confounding variables, omega-3 supplementation was found to be protective against olfactory loss (odds ratio [OR] 0.05, 95% CI 0.003-0.81, P = .03). Tumor functionality was a significant independent predictor for olfactory loss (OR 32.7, 95% CI 1.15-929.5, P = .04). Conclusion Omega-3 supplementation appears to be protective for the olfactory system during the healing period in patients who undergo endoscopic resection of sellar and parasellar masses.

Abstract: The loss of the senses of smell (anosmia) and taste (ageusia) are rather common disorders, affecting up to 20% of the adult population. Yet, this condition has not received the attention it deserves, most probably because per se such a disorder is not life threatening. However, loss of olfactory function significantly reduces the quality of life of the affected patients, leading to dislike in food and insufficient, exaggerated or unbalanced food intake, unintentional exposure to toxins such as household gas, social isolation, depression, and an overall insecurity. Not only is olfactory dysfunction rather prevalent in the healthy population, it is, in many instances, also a correlate or an early indicator of a panoply of diseases. Importantly, olfactory dysfunction is linked to the two most prominent neurodegenerative disorders, Parkinson's disease and Alzheimer's disease. Anosmia and hyposmia (reduced sense of smell) affect a majority of patients years before the onset of cognitive or motor symptoms, establishing olfactory dysfunction as early biomarker that can enable earlier diagnosis and preventative treatments. In the current health crisis caused by SARS-CoV2, anosmia and dysgeusia as early-onset symptoms in virus-positive patients may prove to be highly relevant and crucial for pre-symptomatic Covid-19 detection from a public health perspective, preceding by days the more classical respiratory tract symptoms such as cough, tightness of the chest or fever. Thus, the olfactory system seems to be at the frontline of pathologic assault, be it through pathogens or insults that can lead to or at least associate with neurodegeneration. The aim of this review is to assemble current knowledge from different medical fields that all share a common denominator, olfactory/gustatory dysfunction, and to distill overarching etiologies and disease progression mechanisms.

Abstract: COVID-19, caused by a novel coronavirus, is a persistent global pandemic. It is crucial to examine existing reports to effectively summarize and characterize its clinical course. We used a large-scale meta-analysis to establish prevalence rates for loss of olfaction and gustation in COVID-19 positive patients. PubMed/Medline, Embase, and Web of Sciences were searched for articles published until April 30, 2020. Furthermore, to avoid missing papers, more searches were carried out in the reference lists of covered studies. Articles that mentioned olfactory and/or gustatory disorder in patients with COVID-19 were included for further analysis. Articles that did not report the aforementioned information were excluded. Duplicated articles, reviews, and meta-analysis were excluded as well. The quality of the references was assessed according to the checklist provided by JBI (Joanna Briggs Institute). We used independent extraction of data by multiple observers. The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. The main outcome measures reported were the pooled frequency of olfaction and pooled frequency of gustation disorder in patients with COVID-19 calculated using a random effect model weighted by the study population. The 15 included studies had 3,739 participants which all had confirmed COVID-19. Olfactory and gustatory disorders were assessed and a total number of 1,354 and 1,729 were reported to have taste or smell impairment, respectively. The estimated rate of taste disorder in patients with COVID-19 was 49.0% [95% confidence interval (CI) 34.0-64.0, I2: 96%] (Figure 2). The estimated rate of olfactory disorder in patients with COVID-19 was 61.0% (95% CI 44.0%-75.0%). Our meta-analysis demonstrated high rates of taste (49.0%) and smell (61.0%) disorders in patients with confirmed COVID-19. Results increase the power of recent reports-loss of olfactory and loss of gustation should now routinely be considered in the setting of COVID-19 infection.

Abstract: Olfactory perception has implications for human chemosensory communication and in a broader context, it affects well-being. However, most of the studies investigating the consequences of olfactory ...

Abstract: Introduction: To evaluate the recovery rate of loss of smell (LOS) with objective olfactory testing in COVID-19 patients. Methods: Adults with confirmed COVID-19 and self-reported sudden LOS were prospectively recruited through a public call from the University of Mons (Belgium). Epidemiological and clinical data were collected using online patient-reported outcome questionnaires. Patients benefited from objective olfactory evaluation (Sniffin-Sticks-test) and were invited to attend for repeated evaluation until scores returned to normal levels. Results: From March 22 to May 22, 2020, 88 patients with sudden-onset LOS completed the evaluations. LOS developed after general symptoms in 44.6% of cases. Regarding objective evaluation, 22 patients (25.0%) recovered olfaction within 14 days following the onset of LOS. The smell function recovered between the 16th and the 70th day post-LOS in 48 patients (54.5%). At the time of final assessment at 2 months, 20.5% of patients (N = 18) had not achieved normal levels of olfactory function. Higher baseline severity of olfactory loss measured using Sniffin-Sticks was strongly predictive of persistent loss (p < 0.001). Conclusion: In the first 2 months, 79.5% of patients may expect to have complete recovery of their olfactory function. The severity of olfactory loss, as detected at the first Sniffin-Sticks-test, may predict the lack of mid-term recovery.

Abstract: Associative memory formation and recall in the adult fruit fly Drosophila melanogaster is subserved by the mushroom body (MB). Upon arrival in the MB, sensory information undergoes a profound transformation. Olfactory projection neurons (PNs), the main MB input, exhibit broadly tuned, sustained, and stereotyped responses to odorants; in contrast, their postsynaptic targets in the MB, the Kenyon cells (KCs), are nonstereotyped, narrowly tuned, and only briefly responsive to odorants. Theory and experiment have suggested that this transformation is implemented by random connectivity between KCs and PNs. However, this hypothesis has been challenging to test, given the difficulty of mapping synaptic connections between large numbers of neurons to achieve a unified view of neuronal network structure. Here we used a recent whole-brain electron microscopy (EM) volume of the adult fruit fly to map large numbers of PN-to-KC connections at synaptic resolution. Comparison of the observed connectome to precisely defined null models revealed unexpected network structure, in which a subset of food-responsive PN types converge on individual downstream KCs more frequently than expected. The connectivity bias is consistent with the neurogeometry: axons of the overconvergent PNs tend to arborize near one another in the MB main calyx, making local KC dendrites more likely to receive input from those types. Computational modeling of the observed PN-to-KC network showed that input from the overconvergent PN types is better discriminated than input from other types. These results suggest an 9associative fovea9 for olfaction, in that the MB is wired to better discriminate more frequently occurring and ethologically relevant combinations of food-related odors.

Abstract: The species-specific mode of action for DEET and many other mosquito repellents is often unclear. Confusion may arise for many reasons. First, the response of a single mosquito species is often used to represent all mosquito species. Second, behavioural studies usually test the effect of repellents on mosquito attraction towards human odorants, rather than their direct repulsive effect on mosquitoes. Third, the mosquito sensory neuron responses towards repellents are often not directly examined. A close proximity response assay was used to test the direct repulsive effect of six mosquito repellents on Anopheles coluzzii, Aedes aegypti and Culex quinquefasciatus mosquitoes. Additionally, the behavioural assay and calcium imaging recordings of antennae were used to test the response of An. coluzzii mosquitoes towards two human odorants (1-octen-3-ol and benzaldehyde) at different concentrations, and mixtures of the repellents lemongrass oil and p-menthane-3,8-diol (PMD) with DEET. Anopheles coluzzii mosquitoes were repelled by lemongrass oil and PMD, while Ae. aegypti and Cx. quinquefasciatus mosquitoes were repelled by lemongrass oil, PMD, eugenol, and DEET. In addition, high concentrations of 1-octen-3-ol and benzaldehyde were repellent, and activated more olfactory receptor neurons on the An. coluzzii antennae than lower concentrations. Finally, changes in olfactory responses to repellent mixtures reflected changes in repulsive behaviours. The findings described here suggest that different species of mosquitoes have different behavioural responses to repellents. The data further suggest that high-odour concentrations may recruit repellent-sensing neurons, or generally excite many olfactory neurons, yielding repellent behavioural responses. Finally, DEET can decrease the neuronal and behavioural response of An. coluzzii mosquitoes towards PMD but not towards lemongrass oil. Overall, these studies can help inform mosquito repellent choice by species, guide decisions on effective repellent blends, and could ultimately identify the olfactory neurons and receptors in mosquitoes that mediate repellency.

Abstract: The aim of this study is to investigate the effect of olfactory dysfunction (OD) on the two other chemical senses, namely gustation and the intranasal trigeminal system. Taste and trigeminal function were analyzed in a retrospective cross-sectional study of 178 participants with OD (n = 78 posttraumatic, n = 42 idiopathic, n = 27 post-infectious and n = 31 chronic rhinosinusitis (CRS) OD). All patients had been investigated for OD at our smell and taste outpatient clinic. Evaluation of olfaction was performed by means of the Sniffin’ Sticks test (odor threshold, odor discrimination and odor identification), whereas gustatory function was assessed with the Taste Strips test and the intranasal trigeminal sensitivity by means of the lateralization task. The degree of olfactory impairment was found to depend on the cause of OD, but not on patients’ age. Patients with posttraumatic OD showed lower olfactory function than patients with idiopathic, post-infectious and CRS OD (p = 0.01). Gustatory and trigeminal sensitivity in turn depended on age rather than the cause of olfactory dysfunction. Partial correlations between olfactory, gustatory, and trigeminal scores, with age as covariate, were significant, showing a decrease of taste and trigeminal function proportional to the OD (p < 0.05). The present data suggest that the three chemical senses are closely connected for humans underlining that in case of OD the remaining chemical senses (taste, trigeminal function) tend to decrease rather than compensate as this is seen for sensory loss in other modalities. This finding has direct clinical implications and importance when dealing with smell and taste disorders.

Abstract: Olfactory dysfunction is recognized in neurodevelopmental disorders and may serve as an early indicator of global dysfunction. The present meta-analysis measures olfaction effect sizes in attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and obsessive–compulsive disorder (OCD). Meta-analysis included 320 ADHD, 346 ASD, and 208 OCD individuals as compared to 910 controls. Olfactory performance deficits were small-to-moderate and heterogeneous (d = − 0.42, 95% CI = − 0.59 < δ < − 0.25). Meta-analytic results indicate that olfactory dysfunction is evident in individuals with ASD and OCD, with small-to-negligible effects in ADHD. These findings imply olfactory dysfunction is related to clinical phenotype in ASD and OCD, but not ADHD, and warrant inclusion in clinical assessment and evaluation of certain neurodevelopmental disorders.

Abstract: Olfaction and thermoregulation are key functions for mammals. The former is critical to feeding, mating, and predator avoidance behaviors, while the latter is essential for homeothermy. Aquatic and amphibious mammals face olfactory and thermoregulatory challenges not generally encountered by terrestrial species. In mammals, the nasal cavity houses a bony system supporting soft tissues and sensory organs implicated in either olfactory or thermoregulatory functions. It is hypothesized that to cope with aquatic environments, amphibious mammals have expanded their thermoregulatory capacity at the expense of their olfactory system. We investigated the evolutionary history of this potential trade-off using a comparative dataset of three-dimensional (3D) CT scans of 189 skulls, capturing 17 independent transitions from a strictly terrestrial to an amphibious lifestyle across small mammals (Afrosoricida, Eulipotyphla, and Rodentia). We identified rapid and repeated loss of olfactory capacities synchronously associated with gains in thermoregulatory capacity in amphibious taxa sampled from across mammalian phylogenetic diversity. Evolutionary models further reveal that these convergences result from faster rates of turbinal bone evolution and release of selective constraints on the thermoregulatory-olfaction trade-off in amphibious species. Lastly, we demonstrated that traits related to vital functions evolved faster to the optimum compared to traits that are not related to vital functions.

Abstract: Insects rely on olfaction to locate their host plants by antennae in complex chemical environments Odorant receptor (OR) genes are thought to play a crucial role in the process ORs function together with odorant coreceptors to determine the specificity and sensitivity of olfactory reception The dark black chafer, Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae), is a destructive underground pest To understand the molecular basis of H parallela olfactory reception, an olfactory-biased expressed odorant receptor HparOR27 and HparOrco (HparOR40) were identified from antennal transcriptome analysis and prediction of the sequence structure Tissue expression analysis showed that HparOR27 was mainly expressed in adult antennae throughout developmental stages The functions of HparOR27 were analyzed using the Xenopus laevis oocyte expression system HparOR27 was broadly responsive to three host plant volatiles, including hexanal, lauric acid, and tetradecane Electroantennogram tests confirmed that three ligands were electrophysiologically active in antennae of female adults A Y-tube olfactometer test indicated that hexanal was a repellent for adults of both sexes Taken together, our data support the identification of odorant receptors and provide a molecular basis for eco-friendly pest control

Abstract: Parental experience can modulate the behavior of their progeny. While the molecular mechanisms underlying parental effects or inheritance of behavioral traits have been studied under several enviro...

Abstract: In the mid-19th century, a misconception was born, which understandably persists in the minds of many neuroscientists today. The eminent scientist Albert von Kolliker named a tubular-shaped piece of tissue found in the brains of all mammals studied to date, the tuberculum olfactorium - or what is commonly known as the olfactory tubercle (OT). In doing this, Kolliker ascribed "olfactory" functions and an "olfactory" purpose to the OT. The OT has since been classified as one of several olfactory cortices. However, further investigations of OT functions, especially over the last decade, have provided evidence for roles of the OT beyond olfaction, including in learning, motivated behaviors, and even seeking of psychoactive drugs. Indeed, research to date suggests caution in assigning the OT with a purely olfactory role. Here, I build on previous research to synthesize a model wherein the OT, which may be more appropriately termed the "tubular striatum" (TuS), is a neural system in which sensory information derived from an organism's experiences is integrated with information about its motivational states to guide affective and behavioral responses.

Abstract: Odor-driven behaviors such as feeding, mating, and predator avoidance are crucial for animal survival. The neural pathways processing these behaviors have been well characterized in a number of species, and involve the activity of diverse brain regions following stimulation of the olfactory bulb by specific odors. However, while the zebrafish olfactory circuitry is well understood, a comprehensive characterization linking odor-driven behaviors to specific odors is needed to better relate olfactory computations to animal responses. Here, we used a medium-throughput setup to measure the swimming trajectories of 10 zebrafish in response to 17 ecologically relevant odors. By selecting appropriate locomotor metrics, we constructed ethograms systematically describing odor-induced changes in the swimming trajectory. We found that adult zebrafish reacted to most odorants using different behavioral programs and that a combination of a few relevant behavioral metrics enabled us to capture most of the variance in these innate odor responses. We observed that individual components of natural food and alarm odors do not elicit the full behavioral response. Finally, we show that zebrafish blood elicits prominent defensive behaviors similar to those evoked by skin extract and activates spatially overlapping olfactory bulb domains. Altogether, our results highlight a prominent intra- and inter-individual variability in zebrafish odor-driven behaviors and identify a small set of waterborne odors that elicit robust responses. Our behavioral setup and our results will be useful resources for future studies interested in characterizing innate olfactory behaviors in aquatic animals.

Abstract: Neonicotinoids are pesticides used to protect crops but with known secondary influences at sublethal doses on bees. Honeybees use their sense of smell to identify the queen and nestmates, to signal danger and to distinguish flowers during foraging. Few behavioural studies to date have examined how neonicotinoid pesticides affect the ability of bees to distinguish odours. Here, we use a differential learning task to test how neonicotinoid exposure affects learning, memory, and olfactory perception in foraging-age honeybees. Bees fed with thiamethoxam could not perform differential learning and could not distinguish odours during short and long-term memory tests. Our data indicate that thiamethoxam directly impacts the cognitive processes involved in working memory required during differential olfactory learning. Using a combination of behavioural assays, we also identified that thiamethoxam has a direct impact on the olfactory perception of similar odours. Honeybees fed with other neonicotinoids (clothianidin, imidacloprid, dinotefuran) performed the differential learning task, but at a slower rate than the control. These bees could also distinguish the odours. Our data are the first to show that neonicotinoids have compound specific effects on the ability of bees to perform a complex olfactory learning task. Deficits in decision-making caused by thiamethoxam exposure could be more harmful than other neonicotinoids, leading to inefficient foraging and a reduced ability to identify nest mates.