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Insects have sensitive olfactory systems to interact with environment and respond to the change in host plant conditions. Key genes in the system can be potential targets for developing new and efficient pest behaviour control methods. Riptortus pedestris is an important soybean pest in East Asia and has caused serious damage to the soybean plants in Huang-Huai-Hai region of China. However, the current treatment of pests is dominated by chemical insecticides and lacks efficient sustainable prevention and control technologies. In this study, we identified 49 putative odorant-binding proteins (OBPs) (43 were new genes) and 25 chemosensory proteins (CSPs) (17 were new genes) in R. pedestris genome. These OBP and CSP genes are clustered in highly conserved groups from other hemipteran species in phylogenetic trees. Most RpedOBPs displayed antennal-biased expression. Among the 49 RpedOBPs, 33 were significantly highly expressed in the antennae, including three male-biased and nine female-biased. While many RpedCSPs were detected both in the antennae and in non-antennal tissues, only 11 RpedCSPs displayed antennal-biased expression, in which four RpedCSPs were male-biased and five RpedCSPs were female-biased. Some OBP and CSP genes showed sex-biased expression profiles. Our results not only provide a foundation for future exploration of the functions of RpedOBPs and RpedCSPs but also aid in developing environmentally friendly insecticides in the future. [ABSTRACT FROM AUTHOR]

To investigate the alteration of cerebral blood flow (CBF) and its connectivity patterns in olfactory-related regions of type 2 diabetes mellitus (T2DM) patients using arterial spin labeling (ASL). Sixty-nine patients with T2DM and 63 healthy controls (HCs) underwent ASL scanning using 3.0T magnetic resonance imaging. We compared the CBF values of the olfactory-related brain regions between the two groups and analyzed the correlation between their changes and clinical variables. We also used these regions as seeds to explore the differences in CBF connectivity patterns in olfactory-related brain regions between the T2DM patients and HCs. Compared with the HC group, the CBF of the right orbital part of the inferior frontal gyrus (OIFG), right insula, and bilateral olfactory cortex was decreased in the T2DM patients. Moreover, the duration of the patients was negatively correlated with the CBF changes in the right OIFG, right insula, and right olfactory cortex. The CBF changes in the right OIFG were positively correlated with the Self-Rating Depression Scale scores, those in the right insula were negatively correlated with the max blood glucose of continuous glucose, and those in the right olfactory cortex were negatively correlated with the mean blood glucose of continuous glucose. In addition, the T2DM patients also showed decreased CBF connectivity between the right OIFG and the left temporal pole of the middle temporal gyrus and increased CBF connectivity between the right medial orbital part of the superior frontal gyrus and the right orbital part of the superior frontal gyrus and between the right olfactory cortex and the bilateral caudate and the left putamen. Patients with T2DM have decreased CBF and altered CBF connectivity in multiple olfactory-related brain regions. These changes may help explain why olfactory dysfunction occurs in patients with T2DM, thus providing insights into the neuropathological mechanism of olfactory dysfunction and cognitive decline in T2DM patients. [ABSTRACT FROM AUTHOR]

Summary: Grewia is a tropical berry rich in anthocyanins and antioxidants but highly perishable in nature. In this study, desirable composite blend of overripe Grewia (Phalsa) berries and cantaloupe was sought for conversion to acetic acid. Composition of raw macerate, and the alcoholic and acetic ferments was analysed for sugars, alcohol and acetic acid. The primary alcohol yield varied significantly (5.75–99.44%) with blend composition. Vinegar from select blend attained 4.98% acidity with 138.57 mg mL−1 of phenols and high anthocyanins retention (74.77%). Gompertz model was used to fit the growth curves of S. cerevisiae and A. aceti (R2> 0.92) during fermentation. Presence of ethyl acetate, iso‐pentyl alcohols explained pleasant sweet fruity aroma of resulting vinegar. Thus, high quality functional red fruit vinegar can be obtained to prevent spoilage and utilise the functional potential of this delicate and nutritious berry. [ABSTRACT FROM AUTHOR]

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population. [ABSTRACT FROM AUTHOR]

This study investigates switching costs in landmark-based wayfinding using olfactory and visual landmark information. It has already been demonstrated that there seem to be no switching costs, in terms of correct route decisions, when switching between acoustically and visually presented landmarks. Olfaction, on the other hand, is not extensively focused on in landmark-based wayfinding thus far, especially with respect to modality switching. The goal of this work is to empirically test and compare visual and olfactory landmark information with regard to their suitability for wayfinding including a modality switch. To investigate this, an experiment within a virtual environment was conducted in which participants were walked along a virtual route of 12 intersections. At each intersection, landmark information together with directional information was presented, which was to be memorized and recalled in the following phase, either in the same or in the other modality (i.e., visual or olfactory). The results of the study show that, in contrast to the no-switching costs between auditory and visual landmarks in previous studies, switching costs occur when switching modality from visual to olfactory and vice versa. This is indicated by both longer decision times and fewer correct decisions. This means that a modality switch involving olfactory landmark information is possible but could lead to poorer performance. Therefore, olfaction may still be valuable for landmark-based-wayfinding. We argue that the poorer performance in the switching-condition is possibly due to higher cognitive load and the separate initial processing of odors and images in different cognitive systems. [ABSTRACT FROM AUTHOR]

Objective: Olfactory dysfunction (OD) is a common presenting symptom of COVID‐19 infection. Radiological imaging of the olfactory structures in patients with COVID‐19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention. Methods: PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID‐19 infection and OD, following preferred reporting items for systematic reviews and meta‐analyses guidelines and a PROSPERO‐registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random‐effects meta‐analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID‐19‐associated OD. Results: We included 7 case–control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID‐19 infection and OD (63%, 95% CI = 0.38–0.82) was significantly higher than that in controls (4%, 95% CI = 0.01–0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID‐19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes. Conclusion: Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID‐19 patients. Laryngoscope, 132:1260–1274, 2022 [ABSTRACT FROM AUTHOR]

Abstract Background We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, nose, anosmia, hyposmia, smell, olfactory, ORL, different ENT related symptoms. We reviewed published and peer-reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. Main text Within the included 2549 COVID-19 laboratory-confirmed positive patients, smell affection was reported in 1453 patients (57%). The other reported ENT manifestations were taste disorder (49.2%), headache (42.8%), nasal blockage (26.3%), sore throat (25.7%), runny nose or rhinorrhea (21.3%), upper respiratory tract infection (URTI) (7.9%), and frequent sneezing (3.6%). Conclusion Smell affection in COVID-19 is common and could be one of the red flag signs in COVID-19 infection. With a sensitivity of utilized questionnaire in smell identification, a homogenous universal well-defined COVID-19 questionnaire is needed to make the COVID-19 data collection more sensible.

Abstract Background Formaldehyde is associated with many adverse health effects and is classified as a human carcinogen. Formaldehyde is highly water-soluble and readily absorbed and metabolized by the respiratory mucosa upon inhalation. The histopathological effects of formaldehyde on the nasal mucosa and olfactory nerves in adult New Zealand white rabbits were studied to validate this animal model of inhalational irritants. Results Compared to control group 1 (exposed to air), groups 2 and 3 (exposed to formaldehyde for 90 min and 210 min, respectively) exhibited disrupted nasal tissue, ulcerated epithelial coverings, markedly dilated blood vessels, and increased numbers of inflammatory cells in the lamina propria. The olfactory neuro-epithelium exhibited a reduction in the number of cilia. Many sustentacular cells lost their microvilli. Olfactory nerves exhibited nerve bundle shrinkage within the perineural sheath, leaving an empty space with evidence of edema within the nerve fibers. Conclusion Formaldehyde inhalation has destructive effects on the nasal mucosa and olfactory nerves in adult New Zealand white rabbits. These results validate the use of this animal model to assess the effects of inhalational irritants on the nasal mucosa.

Olfactory sensory neurons are found deep within the nasal cavity at a spatially restricted sheet of sensory epithelium. Due to their location behind the nasal turbinates, accessing these cells for physiological measurements in living animals is challenging, and until recently, not possible. As a further complication, damage to the overlying bone on the dorsal surface of the snout disrupts the negative pressure distribution throughout the nasal cavities, which fundamentally alters how odorants are delivered to the sensory epithelium and the inherent mechanosensory properties of olfactory sensory neurons in live animals. The approach described here circumvents these limitations and allows for optical access to olfactory sensory neurons in mice across time scales ranging from days to months.

Abstract The origin of the neurons and glia in the olfactory system of vertebrates has been controversial, with different cell types attributed to being of ectodermal placode versus neural crest lineage, depending upon the species. Here, we use replication incompetent avian retroviruses to perform a prospective cell lineage analysis of either presumptive olfactory placode or neural crest cells during early development of the chick embryo. Surprisingly, the results reveal a dual contribution from both the olfactory placode and neural crest cells to sensory neurons in the nose and gonadotropin‐releasing hormone neurons migrating to the olfactory bulb. We also confirm that olfactory ensheathing glia cells are solely derived from the neural crest. Finally, our results show that neural crest cells and olfactory placode cells contribute to p63 positive cells, likely to be basal stem cells of the olfactory epithelium. Taken together, these finding provide evidence for previously unknown contributions of neural crest cells to some cell types in the chick olfactory system and help resolve previous discrepancies in the literature. Key Points Modified retroviruses were used to permanently label progenitor cells of the neural crest and olfactory placode for the long‐term lineage analysis of olfactory cells. Both neural crest cells and olfactory placode cells contribute to olfactory neurons and supporting cells of the olfactory epithelium. The gonadotropin‐releasing hormone neurons that arise in the nose and migrate toward the hypothalamus during development also receive contributions from both neural crest and placode cells.

While rates of smoking combustible cigarettes in the United States have trended down in recent years, use of electronic cigarettes (e-cigarettes) has dramatically increased, especially among adolescents. The vast majority of e-cigarette users consume “flavored” products that contain a variety of chemosensory-rich additives, and recent literature suggests that these additives have led to the current “teen vaping epidemic.” This review, covering research from both human and rodent models, provides a comprehensive overview of the sensory implications of e-cigarette additives and what is currently known about their impact on nicotine use. In doing so, we specifically address the oronasal sensory contributions of e-cigarette additives. Finally, we summarize the existing gaps in the field and highlight future directions needed to better understand the powerful influence of these additives on nicotine use.

This study investigates switching costs in landmark-based wayfinding using olfactory and visual landmark information. It has already been demonstrated that there seem to be no switching costs, in terms of correct route decisions, when switching between acoustically and visually presented landmarks. Olfaction, on the other hand, is not extensively focused on in landmark-based wayfinding thus far, especially with respect to modality switching. The goal of this work is to empirically test and compare visual and olfactory landmark information with regard to their suitability for wayfinding including a modality switch. To investigate this, an experiment within a virtual environment was conducted in which participants were walked along a virtual route of 12 intersections. At each intersection, landmark information together with directional information was presented, which was to be memorized and recalled in the following phase, either in the same or in the other modality (i.e., visual or olfactory). The results of the study show that, in contrast to the no-switching costs between auditory and visual landmarks in previous studies, switching costs occur when switching modality from visual to olfactory and vice versa. This is indicated by both longer decision times and fewer correct decisions. This means that a modality switch involving olfactory landmark information is possible but could lead to poorer performance. Therefore, olfaction may still be valuable for landmark-based-wayfinding. We argue that the poorer performance in the switching-condition is possibly due to higher cognitive load and the separate initial processing of odors and images in different cognitive systems.

Special senses are those regulated by the cranial nerves, and are of general interest for practitioners of anaesthesia and intensive care. This article gives a brief description of the neural mechanisms and pathways responsible for vision, hearing, smell, balance and taste. [ABSTRACT FROM AUTHOR]

BackgroundAedes albopictus is a globally invasive mosquito and a major vector of arboviruses, including dengue, Zika and Chikungunya. Olfactory-related behaviors, particularly host-seeking, offer opportunities to disrupt the disease-transmission process. A better understanding of odorant receptors (ORs) may assist in explaining host selection and location, and contribute to novel strategy of vector control.MethodsBased on previous prediction of 158 putative odorant receptors by Ae. albopictus genome analysis, 29 AalORs were selected for tissue-specific expression profiles in the present study. AalOrco (AalOR7), AalOR10 and AalOR88, highly expressed in female olfactory tissues, were chosen for further structure predictions as well as functional validation including calcium imaging assay in human embryonic kidney (HEK293) cells and RNA interference assay in Ae. albopictus. We also conducted electrophysiological and behavioral assays in mosquitoes after RNA interference of the three genes to determine their roles in host-seeking.ResultsThe results support previous conclusions that individual conventional (ORXs) and Orco can form heteromeric complexes to recognize odorants and respond to components of human volatiles in HEK293 cells. The reduction of AalOrco transcript levels led to a significant decrease in host-seeking and confusion in host preference. In contrast, AalOR10 and AalOR88 knockdown mosquitoes showed no significant behavioral differences compared with controls. The functions of conventional ORs at least AalOR10 and AalOR88 are abolished with inhibited expression of the Orco gene orthologs, along with the concomitant relevant olfactory behavior.ConclusionsCombining structural and functional data, we conclude that the product of the Orco gene in this mosquito is crucial for transmitting olfactory signaling and conventional ORs contribute directly to odorant recognition. Our results provide insight into the linkage between odorant receptors and host-seeking in this important vector species.

Although the anatomy of the nasal fossa is broadly similar among terrestrial mammals, differences are evident in the intricacies of nasal turbinal architecture, which varies from simple scroll-like to complex branching forms, and in the extent of nonsensory and olfactory epithelium covering the turbinals. In this study, detailed morphological and immunohistochemical examinations and quantitative measurements of the turbinals and epithelial lining of the nasal fossa were conducted in an array of species that include the gray squirrel, bobcat, coyote, and white-tailed deer. Results show that much more of the nose is lined with olfactory epithelium in the smallest species (gray squirrel) than in the larger species. In two species with similar body masses, bobcat and coyote, the foreshortened felid snout influences turbinal size and results in a decrease of olfactory epithelium on the ethmoturbinals relative to the longer canine snout. Ethmoturbinal surface area exceeds that of the maxilloturbinals in all four sampled animals, except the white-tailed deer, in which the two are similar in size. Combining our results with published data from a broader array of mammalian noses, it is apparent that olfactory epithelial surface area is influenced by body mass, but is also affected by aspects of life history, such as diet and habitat, as well as skull morphology, itself a product of multiple compromises between various functions, such as feeding, vision, and cognition. The results of this study warrant further examination of other mammalian noses to broaden our evolutionary understanding of nasal fossa anatomy. Anat Rec, 299:840-852, 2016. © 2016 Wiley Periodicals, Inc.

Abstract To determine the prevalence and clinical features of olfactory and taste disorders among coronavirus disease 2019 (COVID-19) patients in China. A cross-sectional study was performed in Wuhan from April 3, 2020 to April 15, 2020. A total of 187 patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) completed face-to-face interviews or telephone follow-ups. We found that the prevalence of olfactory and taste disorders was significantly lower in the Chinese cohort than in foreign COVID-19 cohorts. Females were more prone to olfactory and taste disorders. In some patients, olfactory and taste disorders precede other symptoms and can be used as early screening and warning signs.

Ketamine is an anesthetic agent with sedative and analgesic properties frequently used in surgery. However, particular anesthetic substances need to be applied for different diseases and surgical procedures. Can ketamine be used in all operations and in all patients with an additional disease? The purpose of this study was to determine the neurotoxic or neuroprotective effects of different dosages of ketamine in a glutamate-derived toxicity model in olfactory, cortex and cerebellum cell cultures. Glutamate 10−5 mM was added to all culture groups with the exception of the negative control group. Cells were exposed to four different dosages of ketamine for 24 h. At the end of the experiment, analyses were conducted using MTT, total antioxidant capacity (TAC), total oxidant status (TOS) and flow cytometry (annexin V apoptosis marker) tests. The highest viability rate was obtained at the lowest ketamine dosage, at approximately 80% in cerebellum cells, but less than 75% in cortex and olfactory culture cells. Based on our study findings, although ketamine is an NMDA antagonist, it causes an increase in toxicity levels and a decrease in cell viability. Ketamine use should therefore be avoided in neurological events in which glutamate levels increase significantly.

Abstract The olfactory pathway is composed of peripheral sinonasal and central sensorineural components. The wide variety of different pathologies that can affect the olfactory pathway reflect this complex anatomical relationship. Localising olfactory pathology can present a challenge to the reporting radiologist. This imaging review will illustrate the normal anatomy of the olfactory system and describe a systematic approach to considering olfactory dysfunction. Key concepts in image interpretation will be demonstrated using examples of olfactory pathway pathologies.

Reward exploitation and aversion are mediated in part by the locus coeruleus (LC), a brainstem structure significantly involved in learning and memory via the release of norepinephrine. Different LC firing patterns are associated with different functions. Previously, we have shown that high tonic and phasic LC activation signal negative and positive valence, respectively, via basolateral amygdala (BLA) circuitry. Tonic LC activation is associated preferentially with BLA-central amygdala (CeA) activation, while phasic LC stimulation preferentially recruits the BLA-nucleus accumbens (NAc) pathway. Here, we ask if phasic and tonic LC activation-associated valence learning requires different adrenoceptors in the BLA, in comparison with the odor valence learning induced by natural reward and aversive conditioning. Using optogenetic activation of the LC and local drug infusions in the BLA, we show that phasic LC activation-induced positive odor valence learning is dependent on both α 1 and β-adrenoceptors, whereas tonic LC activation induced-negative odor valence learning depends on β-adrenoceptors only. In parallel, both α 1 and β-adrenoceptors were required in the odor valence learning induced by reward while aversive conditioning was dependent on β-adrenoceptors. Phasic stimulation and reward conditioning likewise activated more NAc-projectors of the BLA, in comparison to tonic and aversive conditioning. There was a higher proportion of α1+ cells in the NAc-projectors compared to CeA-projectors in the BLA. Together, these results provide insight into the mechanisms underlying the effects of tonic and phasic activation of the LC, and more generally, negative and positive valence signaling. [ABSTRACT FROM AUTHOR]

Background: A substantial proportion of coronavirus disease‐2019 (COVID‐19) patients demonstrate olfactory and gustatory dysfunction (OGD). Self‐reporting for OGD is widely used as a predictor of COVID‐19. Although psychophysical assessment is currently under investigation in this role, the sensitivity of these screening tests for COVID‐19 remains unclear. In this systematic review we assess the sensitivity of self‐reporting and psychophysical tests for OGD. Methods: A systematic search was performed on PubMed, EMBASE, and ClinicalTrials.gov from inception until February 16, 2021. Studies of suspected COVID‐19 patients with reported smell or taste alterations were included. Data were pooled for meta‐analysis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were reported in the outcomes. Results: In the 50 included studies (42,902 patients), self‐reported olfactory dysfunction showed a sensitivity of 43.9% (95% confidence interval [CI], 37.8%‐50.2%), a specificity of 91.8% (95% CI, 89.0%‐93.9%), and a DOR of 8.74 (95% CI, 6.67‐11.46) for predicting COVID‐19 infection. Self‐reported gustatory dysfunction yielded a sensitivity of 44.9% (95% CI, 36.4%‐53.8%), a specificity of 91.5% (95% CI, 87.7%‐94.3%), and a DOR of 8.83 (95% CI, 6.48‐12.01). Olfactory psychophysical tests analysis revealed a sensitivity of 52.8% (95% CI, 25.5%‐78.6%), a specificity of 88.0% (95% CI, 53.7%‐97.9%), and a DOR of 8.18 (95% CI, 3.65‐18.36). One study used an identification test for gustatory sensations assessment. Conclusion: Although demonstrating high specificity and DOR values, neither self‐reported OGD nor unvalidated and limited psychophysical tests were sufficiently sensitive in screening for COVID‐19. They were not suitable adjuncts in ruling out the disease. [ABSTRACT FROM AUTHOR]

The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients. [ABSTRACT FROM AUTHOR]

Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction. [ABSTRACT FROM AUTHOR]

Inhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration act as gatekeepers for neural activity, synaptic plasticity, and the formation of sensory representations. Conversely, interneurons that selectively inhibit other interneurons can open gates through disinhibition. In the anterior piriform cortex, relief of inhibition permits associative LTP of excitatory synapses between pyramidal neurons. However, the interneurons and circuits mediating disinhibition have not been elucidated. In this study, we use an optogenetic approach in mice of both sexes to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent interneuron classes: somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that LTP is gated by the inactivation SST or PV interneurons and by the activation of VIP interneurons. Further, VIP interneurons strongly inhibit putative SST cells during LTP induction but only weakly inhibit PV interneurons. Together, these findings suggest that VIP interneurons mediate a disinhibitory circuit that gates synaptic plasticity during the formation of olfactory representations. [ABSTRACT FROM AUTHOR]

Introduction: Our visual, auditory, and tactile perception is not solely determined by what we process at a given moment in time, but also determined by what we perceived recently. These sequential effects can either be negative (repulsive) or positive (assimilative). Here, we investigated whether such sequential effects also occur in odor perception. Method: Participants rated a sequence of 40 different odors (varying widely in hedonic valence) on four different characteristics (intensity, familiarity, valence, and arousal). For each of these characteristics, we conducted an inter-trial analysis, based on whether the rating on the preceding trial was low or high. Results: We found a positive serial dependence for both odor intensity and familiarity ratings. That is, the rating on the current trial was higher when the rating on the previous trial was high than when the rating on the previous trial was low. We observed no sequential effects for odor valence and arousal ratings. Conclusion: The olfactory system integrates previous stimuli into the current perception of intensity and familiarity. Implications The current findings may be relevant for marketing applications and may guide the design and use of olfactory-enhanced virtual and augmented reality systems. [ABSTRACT FROM AUTHOR]

Pain inadequate treatment is frequent in modern society, with major medical, ethical, and financial implications. In many healthcare environments, pain is quantified prevalently through subjective measures, such as self-reports from patients or health care providers’ personal experience. Recently, automatic diagnostic tools have been developed to detect and quantify pain more “objectively” from facial expressions. However, it is still unclear if these approaches can distinguish pain from other aversive (but painless) states. In this article, we analyzed the facial responses from a database of video-recorded facial reactions evoked by comparably-unpleasant painful and disgusting stimuli. We modeled this information as function of subjective unpleasantness, as well as the specific state evoked by the stimuli (pain vs. disgust). Results show that a machine learning algorithm could predict subjective pain unpleasantness from facial information, but mistakenly detected unpleasant disgust, especially in those models relying in great extent on the brow lowerer. Importantly, pain and disgust could be disentangled using an ad hoc algorithm that rely on combined information from the eyes and the mouth. Overall, the facial expression of pain contains both specific and unpleasantness-related information shared with disgust. Automatic diagnostic tools should be guided to account for this confounding effect. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence of gustatory and olfactory impairment and its correlation with the severity of SARS-Cov-2 infection as per WHO guidelines. Methods: A total of 241 patients of both gender having age from 15-80 years were included in the study. It was cross Sectional study conducted at SARS-COV-2 Isolation wards of Pakistan institute of medical science Islamabad from 15thSeptember 2020 to 15th January 2021. Convenient sampling technique was used to collect data. A proforma was designed for this purpose. Participants were divided into 3 groups on the basis of age. Group-1 (15-30 years), group-2 (31-50 years) and group 3 (51-80 years). Further the participants were graded into mild, moderate and severe stages of Sars-Cov-2 infection according to WHO guidelines. Statistical analysis was performed by using SPSS version 20. Results: In this study 66% were male and 34% population were the female. Regarding the age groups 72% population were from the group-3. Results of study shows 47% in mild stage, 45% in moderate stage and 8% severe stage. The results regarding the Gustatory and Olfactory impairment showed that 126 had gustatory impairment while 130 patients had olfactory impairment. Conclusion: We found strong relationship of olfactory and gustatory changes associated with SARS-COV-2 patients. It is premature to conclude that taste and smell changes are strongly linked to SARS-COV-2 diagnosis. Further multi center researches are required to find out possible pathophysiological mechanism. [ABSTRACT FROM AUTHOR]

Background: Olfactory Sensory Neuron (OSN) axons project from the zebrafish olfactory epithelium to reproducible intermediate target locations in the olfactory bulb called protoglomeruli at early stages in development. Two classes of OSNs expressing either OMP or TRPC2 exclusively target distinct, complementary protoglomeruli. Using RNAseq, we identified axon guidance receptors nrp2a and nrp2b, and their ligand sema3fa, as potential guidance factors that are differentially expressed between these two classes of OSNs. Methods: To investigate their role in OSN axon guidance, we assessed the protoglomerular targeting fidelity of OSNs labeled by OMP:RFP and TRPC2:Venus transgenes in nrp2a, nrp2b, or sema3fa mutants. We used double mutant and genetic interaction experiments to interrogate the relationship between the three genes. We used live time-lapse imaging to compare the dynamic behaviors of OSN growth cones during protoglomerular targeting in heterozygous and mutant larvae. Results: The fidelity of protoglomerular targeting of TRPC2-class OSNs is degraded in nrp2a, nrp2b, or sema3fa mutants, as axons misproject into OMP-specific protoglomeruli and other ectopic locations in the bulb. These misprojections are further enhanced in nrp2a;nrp2b double mutants suggesting that nrp2s work at least partially in parallel in the same guidance process. Results from genetic interaction experiments are consistent with sema3fa acting in the same biological pathway as both nrp2a and nrp2b. Live time-lapse imaging was used to examine the dynamic behavior of TRPC2-class growth cones in nrp2a mutants compared to heterozygous siblings. Some TRPC2-class growth cones ectopically enter the dorsal-medial region of the bulb in both groups, but in fully mutant embryos, they are less likely to correct the error through retraction. The same result was observed when TRPC2-class growth cone behavior was compared between sema3fa heterozygous and sema3fa mutant larvae. Conclusions: Our results suggest that nrp2a and nrp2b expressed in TRPC2-class OSNs help prevent their mixing with axon projections in OMP-specific protoglomeruli, and further, that sema3fa helps to exclude TRPC2-class axons by repulsion from the dorsal-medial bulb. [ABSTRACT FROM AUTHOR]

Background: Impairments of olfactory and speech function are likely early prodromal symptoms of α‐synucleinopathy. Objective: The aim of this study is to assess whether dysprosody is present in isolated rapid eye movement sleep behavior disorder (iRBD) with hyposmia/anosmia and a normal nigrostriatal system. Methods: Pitch variability during speech was investigated in 17 iRBD subjects with normal olfactory function (iRBD‐NOF), 30 iRBD subjects with abnormal olfactory function (iRBD‐AOF), and 50 healthy controls. iRBD subjects were evaluated using the University of Pennsylvania Smell Identification Test and [123I]‐2ß‐carbomethoxy‐3ß‐(4‐iodophenyl)‐N‐(3‐fluoropropyl)‐nortropane dopamine transporter single‐photon emission computed tomography (DAT‐SPECT). All iRBD subjects completed the 24‐month follow‐up with DAT‐SPECT, speech, and olfactory testing. Results: At baseline, only iRBD‐AOF showed monopitch when compared to iRBD‐NOF (P = 0.04) and controls (P = 0.03), with no difference between iRBD‐NOF and controls (P = 1). At follow‐up, dysprosody progressed only in iRBD‐AOF with abnormal DAT‐SPECT (P = 0.03). Conclusion: Prosody is impaired in hyposmic but not in normosmic iRBD subjects before the nigrostriatal dopaminergic transmission is affected (Braak stage 2). © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

For military Veterans (MVs) to obtain effective care, nurses must be alert to olfaction issues, ask the right questions, and be aware of the various sensitivities required to obtain a helpful history. Diagnostic queries and applicable education can promote patient-centered holistic care to help MVs manage symptoms and learn new coping strategies for their olfaction issues. [ABSTRACT FROM AUTHOR]

Aim: Sino-nasal tract tumours constitute 3% of the head and neck malignancies. Among these tumours, neuroectodermal tumours are rare with histo-morphological and immunohistochemical overlap making them a challenge for the pathologist. We included Ewing's/PNET, olfactory neuroblastoma (OFN), mucosal malignant melanomas (MMM), Melanotic neuroectodermal tumour of infancy (MNTI), small-cell neuroendocrine carcinoma (SNEC), and the newest entity Adamantinoma like Ewing's sarcoma (ALES) as part of the neuroectodermally derived tumours of the sino-nasal tract. The last three entities were added to the existing ones, which also has been emphasized in this paper. Methods and results: A comprehensive analysis was done on all neuroectodermally derived tumours from 2016 to 2020. A total of 18 cases were collected, which included OFN (10 cases), SNEC (2 cases), MMM (2 cases), Ewing's/PNET (2 cases), MNTI (1 case), and ALES (1 case). The most common presentation in NE tumours was nasal obstruction (80–100%). Except for OFN, all other tumours were confined to the nasal and paranasal sinuses. 4/10 cases of OFN showed orbital extension. Cervical lymph-node metastasis was seen in 50% of cases of SNEC and MMM groups. An array of relevant immune-histochemical markers were performed. The marker expression was very subtle among the groups. On follow-up, recurrence was seen in the OFN and MMM groups in 30 and 50%, respectively. Metastasis was seen in SNEC group (100%) and OFN group (10%). Conclusion: As sino-nasal neuroectodermal tumours pose a diagnostic challenge and have different therapies and are prognostically different, the pathologist must be aware of the subtle morphological, immunohistochemical clues which have been dealt with in-depth in this study. [ABSTRACT FROM AUTHOR]

As a primary determinant of nasal physiological functions, the nasal morphology and its effects on the airflow dynamics have been extensively studied in literature. However, gross flow features reported in literature are mostly obtained from subjects at similar ages, while studies focusing on nasal subjects with distinct age differences are significantly less. To advance current understandings of nasal airflow dynamics in the context of age diversity, this study employed three anatomically accurate nasal cavity models with distinct age features (5‐, 24‐ and 77‐year‐old models) and numerically compared the physiological nasal airflow fields within these nasal cavity models. To demonstrate the validity of the present numerical models, in vivo rhinomanometry measurement was conducted on the 24‐year‐old female nasal model, and key anatomical features and pressure‐flow curves of all three models were compared with models with similar age features in literature work. Apart from results comparison based on conventional velocity flow fields and wall shear stress distributions, a method for quantifying flow partitions in confined airway spaces was developed to reveal the proportions of fractional flow that enters the olfactory region. Our results revealed dramatic intersubject discrepancies between considered nasal cavity models, especially for the fractional flow that enters the olfactory region. Specifically, the 5‐year‐old girl nasal model received the highest proportion of fractional flow, which accounts for 13.3% ~ 15% of overall inhalation flow rates under different activity levels. For the 24‐year‐old female model, on the contrary, the olfactory fractional flow was dramatically reduced (with a local to overall percentage around 4.3%–7.7%). Finally, for the elderly subject—77‐year‐old male model, minimum level of olfactory flux was observed with a local to overall percentage ranging between 3.1% and 4.9% for considered wide range of inhalation flow rates. Therefore, the local flow intersubject variation can reach nearly fourfold. The vast local flow difference is mainly due to the inherent anatomical features (e.g., immature nasal turbinate structure in the child model, the partial narrowing superior nasal valve in the elder model). The results may further lead to discrepant health effects associated with inhalation exposure to airborne particles. [ABSTRACT FROM AUTHOR]

Massive Open Online Courses (MOOCs) have been described as a "next development of networked learning", and they have the potential to mediate sensory learning. To understand this phenomenon, the present systematic review examines the research techniques, subjects, and trends of MOOC research on sensory learning, in order to provide a thorough understanding of the MOOC relevant to sensory (olfactory) learning phenomena by evaluating 65 (four studies are about multisensorial learning and 61 are about multisensorial empirical MOOCs researches) empirical MOOC studies published between 2008 and 2021 by searching through databases: PubMed, Scopus, Web of Science, and Google Scholar. The results indicated that most studies were based on quantitative research methods followed by mixed research methods and the qualitative research approaches; most of the studies were surveys, followed by platform databases and interviews; almost half of the studies were conducted using at least two methods for data collection: survey and interviews; most were replicated. The most highlighted subjects included student retention, learning experience, social learning, and engagement. Implications and studies into the future have been considered in order to obtain a more evolved understanding of the acquisition of knowledge through the senses. [ABSTRACT FROM AUTHOR]

Background: Anosmia-hyposmia and dysgeusia are common symptoms of mild-to-moderate COVID-19 cases. They are usually, but not always, reversible and the cause is unknown. Methodology: Proteonomic similarity searching (BLAST) was used to test whether SARS-CoV-2 has an unusual degree of similarity to human olfactory receptors as compared with other viruses. Results: SARS-CoV-2 displays two orders of magnitude more similarities to human olfactory receptors than does any other upper respiratory virus or rhinovirus and five times as many similarities as cold-causing coronaviruses. Conclusions: It is hypothesized that IgA antibodies produced against SARS-CoV-2 proteins and secreted in saliva and mucus bind to and block human olfactory receptors. These antibodies cause the reversible form of anosmia-hyposmia associated with COVID-19 infection. The mimicry may also, rarely, lead to autoimmune disease against neurons expressing olfactory receptors, in which case oral or nasal steroids may be therapeutic.

Abstract Background A rare genetic disorder called Kallmann syndrome results from a defect in the neuronal migration of olfactory axons and gonadotropin-releasing hormone neurons. MR imaging helps in confirming the diagnosis of Kallmann syndrome with characteristic morphological findings in the brain, in clinically suspicious cases of hypogonadotropic hypogonadism with anosmia/hyposmia. Case presentation A 15-year-old male teenager presented with complaints of a small penis and anosmia. Hormonal assay of gonadotropins and testosterone revealed low serum concentrations. MRI brain revealed the absence of the olfactory bulbs in the olfactory grooves and hypoplastic olfactory sulcus. With the gonadotropic hormonal assay showing low levels and characteristic MR imaging features of absent olfactory tracts and olfactory sulcus, the diagnosis of Kallmann syndrome was confirmed. Conclusions Morphological abnormalities of olfactory tracts and olfactory sulcus can be accurately depicted with MR imaging through anterior fossa in the coronal plane. Therefore, MR imaging of the brain plays a significant role in diagnosing uncommon Kallmann syndrome and other associated brain abnormalities.

Abstract Background The lack of objective data makes it difficult to establish the prognostic value of chemosensitive disorders in coronavirus disease 2019 (COVID-19) patients. We aimed to prospectively monitor patients diagnosed with COVID-19 to see if the severity of olfactory and gustatory dysfunction associates with subsequent disease severity. Methods Multicentre prospective study that recruited 106 COVID-19 subjects at diagnosis. Chemosensitive functions were assessed with psychophysical tests within 4 days of clinical onset, at 10 and 20 days. Daily body temperature and oxygen saturation were recorded as markers of disease severity alongside need for hospitalisation. The correlation between olfactory and gustatory scores and disease severity was assessed with linear regression analysis. Results At T0, 71 patients (67%) presented with olfactory dysfunction while gustatory impairment was detected in 76 cases (65.6%). Chemosensitive disorders gradually improved over the observation period. No significant correlations were found between T0 chemosensitive scores and final disease severity. The correlation between olfactory scores and fever proved significant at T2 (p = 0.05), while the relationship with gustatory scores was significant at T1 (p = 0.01) and T2 (p

Organophosphate insecticides are known to inhibit the activity of enzyme acetylcholinesterase. They affect olfactory learning and memory formation in honeybees. These insecticides cause mushroom body inactivation in honeybees, but their influence on other brain regions involved in olfactory perception and memory is unknown. The goal of this study was to study the effects of organophosphate insecticide diazinon on carnolian honeybee (Apis mellifera carnica) acetylcholinesterase activity in the olfactory brain regions of antennal lobe, mushroom body and lateral procerebrum (lateral horn). The lamina, medulla and lobula of optic lobes were also analyzed. The level of acetylcholinesterase activity was visualized using the histochemical staining method. Densitometric analysis of histochemical signals indicated that diazinon inhibited acetylcholinesterase activity only in the lip of calyces of mushroom body, but not in other analyzed olfactory regions, antennal lobe and lateral procerebrum. The visual brain system optic lobes were also unaffected. This is in accordance with the literature reporting that mushroom body is the main brain center for olfactory learning and memory formation in honeybees.

Qingrong OuYang,1,* Yinxu Wang,2,* Yun-wei Zhang,1 Ming Yu,1 Xiaoming Wang3 1Department of Neurology, Suining Central Hospital, Sui Ning 629000, People’s Republic of China; 2Department of Rehabilitation Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Yu; Xiaoming Wang Email yuming609800@163.com; wangxm238@163.comBackground: Olfactory disorder is one of the commonly appearing symptoms in diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD). However, reports of olfactory changes in multiple sclerosis (MS) are scarce and usually ignored or seldom recognized by clinicians. The majority of current research is based on subjective answers obtained by smelling odorants.Objective: To gain better insights into the central brain regions involved in the olfactory process. We measured preliminary contrast assessment characteristics of brain activation in MS patients and healthy controls using functional magnetic resonance imaging (fMRI) under an odor stimulation task.Methods: Olfactory event-related fMRI was used to assess the olfactory network neuronal activity during passively inhaled volatile gases of lavender and rose solutions alternately in 18 MS patients and 20 healthy sex- and age-matched adults. Spearman correlation analysis was conducted between the lesions in central and olfactory-induced activated brain regions.Results: We observed significant reductions in the number of activated brain areas compared with healthy controls in MS patients under a standard activation mode; the right insula, right amygdala, right inferior frontal gyrus, right frontal middle gyrus, and left supramarginal gyrus were activated in MS patients (t = 2.04, P < 0.05). Meanwhile, the intensity of the activated olfactory brain network revealed attenuation. The Spearman correlation analysis indicated the distribution and number of demyelination lesions, exerting a little impact on major activation of brain regions during olfactory stimulation (r = – 0.524, P = 0.054).Conclusion: This study establishes that olfaction-related brain regions were altered in patients with MS confirmed by fMRI. The finding refreshes the awareness that olfactory disturbance involved just in structural pathology like olfactory bulbs and tracts or olfactory sulcus, which reportedly is responsible for the deficits.Keywords: multiple sclerosis, olfactory, magnetic resonance imaging, brain

Competition has increased due to the proliferation of different brands of malt drinks in Nigeria. Thus, manufacturers and brand managers of malt drinks need to explore strategic approaches to acquiring and retaining their customers. However, this paper assessed the multisensory attributes of malt drinks and consumer purchase decisions in South-Eastern Nigeria. The study population comprises consumers of Maltina, Malta Guinness, Amstel Malta, Dubic Malt, and Grand Malt in South-Eastern Nigeria. A sample size of 384 consumers of malt brands was determined using Topman formula. A convenience sampling technique was adopted, and respondents were drawn from five states such as Abia, Anambra, Ebonyi, Enugu, and Imo. The study adopted a cross-sectional survey research method. Cronbach’s alpha and composite reliability were estimated to check the internal consistency of the study constructs. The structural equation modeling technique was used in data analysis. Findings revealed that the visual attribute of malt has a significant positive relationship with consumer purchase decisions. It was also revealed that malt brand gustatory attribute has a significant positive relationship with consumer purchase decisions. Similarly, it was revealed that the tactile attribute of malt brand has a significant positive relationship with consumer purchase decisions. Finally, it was revealed that the malt brand olfactory attribute has a significant positive relationship with consumer purchase decisions. Therefore, manufacturers and brand managers of malt should improve on packaging their malt brands by strategically adapting a multisensory synergy to guarantee wider consumer purchase and experience toward ensuring more customer satisfaction, patronage, and increased profits for the organizations. AcknowledgmentsIn the course of this study, a few researchers assisted and contributed immensely in developing the methodology for the study. They include: Prof. Donatus Chigbo Ngige, Dr. Ezeh Precious, Dr. Osegbue Francis Ifeanyi, Dr. Ofor Theresa Nkechi, Prof. Mary Margret N. Okeke, Mrs Vivian C. Anetoh and Dr. Egbeh Placid C. Thank you very much and God bless you all. Also, we thank our respondents who supplied us with the needed data that made this study a reality.

The cranial nerves are the pathways through which environmental information (sensation) is directly communicated to the brain, leading to perception, and giving rise to higher cognition. Because cranial nerves determine and modulate brain function, invasive and non-invasive cranial nerve electrical stimulation methods have applications in the clinical, behavioral, and cognitive domains. Among other neuromodulation approaches such as peripheral, transcranial and deep brain stimulation, cranial nerve stimulation is unique in allowing axon pathway-specific engagement of brain circuits, including thalamo-cortical networks. In this review we amalgamate relevant knowledge of 1) cranial nerve anatomy and biophysics; 2) evidence of the modulatory effects of cranial nerves on cognition; 3) clinical and behavioral outcomes of cranial nerve stimulation; and 4) biomarkers of nerve target engagement including physiology, electroencephalography, neuroimaging, and behavioral metrics. Existing non-invasive stimulation methods cannot feasibly activate the axons of only individual cranial nerves. Even with invasive stimulation methods, selective targeting of one nerve fiber type requires nuance since each nerve is composed of functionally distinct axon-types that differentially branch and can anastomose onto other nerves. None-the-less, precisely controlling stimulation parameters can aid in affecting distinct sets of axons, thus supporting specific actions on cognition and behavior. To this end, a rubric for reproducible dose-response stimulation parameters is defined here. Given that afferent cranial nerve axons project directly to the brain, targeting structures (e.g. thalamus, cortex) that are critical nodes in higher order brain networks, potent effects on cognition are plausible. We propose an intervention design framework based on driving cranial nerve pathways in targeted brain circuits, which are in turn linked to specific higher cognitive processes. State-of-the-art current flow models that are used to explain and design cranial-nerve-activating stimulation technology require multi-scale detail that includes: gross anatomy; skull foramina and superficial tissue layers; and precise nerve morphology. Detailed simulations also predict that some non-invasive electrical or magnetic stimulation approaches that do not intend to modulate cranial nerves per se, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), may also modulate activity of specific cranial nerves. Much prior cranial nerve stimulation work was conceptually limited to the production of sensory perception, with individual titration of intensity based on the level of perception and tolerability. However, disregarding sensory emulation allows consideration of temporal stimulation patterns (axon recruitment) that modulate the tone of cortical networks independent of sensory cortices, without necessarily titrating perception. For example, leveraging the role of the thalamus as a gatekeeper for information to the cerebral cortex, preventing or enhancing the passage of specific information depending on the behavioral state. We show that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and how specific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

Methamphetamine (Meth) is a predominantly abused neurostimulant, and its abuse is often associated with multiple neurological symptoms. Olfaction, the sense of smell, is a highly neurotransmission-dependent physiological process; however, the effect of Meth on olfactory function and its underlying mechanisms remain largely unknown. This study aimed to explore the impact of Meth abuse on the olfactory system and the potential mechanisms. Chronic Meth abuse was induced by daily administration of Meth in male mice for 4 weeks, and we then systematically examined olfactory performance. Behavioral tests found that Meth-treated animals showed increased olfactory threshold, decreased olfactory sensitivity, reduced olfactory-dependent discrimination, and difficulty in seeking buried food. Notably, the increased deposition of α-synuclein (α-syn) in the olfactory bulb was detected. Adeno-associated virus (AAV)-mediated α-syn intervention therapy in the olfactory bulb significantly alleviated Meth-induced olfactory function impairment, and 8 weeks of aerobic exercise showed similar effects through the same principle of α-syn intervention. Notably, exercise-mediated reduction of α-syn inhibited abnormal firing activity and restored the inhibitory synaptic regulation of mitral cells in the olfactory bulb. These findings suggest the involvement of α-syn in the pathogenic mechanisms of Meth-induced olfactory dysfunction and shed light on the possible therapeutic applications of aerobic exercise in Meth-induced olfactory dysfunction.

Reward exploitation and aversion are mediated in part by the locus coeruleus (LC), a brainstem structure significantly involved in learning and memory via the release of norepinephrine. Different LC firing patterns are associated with different functions. Previously, we have shown that high tonic and phasic LC activation signal negative and positive valence, respectively, via basolateral amygdala (BLA) circuitry. Tonic LC activation is associated preferentially with BLA-central amygdala (CeA) activation, while phasic LC stimulation preferentially recruits the BLA-nucleus accumbens (NAc) pathway. Here, we ask if phasic and tonic LC activation-associated valence learning requires different adrenoceptors in the BLA, in comparison with the odor valence learning induced by natural reward and aversive conditioning. Using optogenetic activation of the LC and local drug infusions in the BLA, we show that phasic LC activation-induced positive odor valence learning is dependent on both α1 and β-adrenoceptors, whereas tonic LC activation induced-negative odor valence learning depends on β-adrenoceptors only. In parallel, both α1 and β-adrenoceptors were required in the odor valence learning induced by reward while aversive conditioning was dependent on β-adrenoceptors. Phasic stimulation and reward conditioning likewise activated more NAc-projectors of the BLA, in comparison to tonic and aversive conditioning. There was a higher proportion of α1+ cells in the NAc-projectors compared to CeA-projectors in the BLA. Together, these results provide insight into the mechanisms underlying the effects of tonic and phasic activation of the LC, and more generally, negative and positive valence signaling.

Focal intranasal drug delivery to the olfactory cleft is a promising avenue for pharmaceuticals targeting the brain. However, traditional nasal sprays often fail to deliver enough medication to this specific area. We present a laminar fluid ejection (LFE) method for precise delivery of medications to the olfactory cleft. Using a 3D-printed model of the nasal passages, we determined the precise velocity and angle of insertion needed to deposit fluid at the olfactory cleft. Then, we conducted three proof-of-concept in-vivo imaging studies to confirm olfactory delivery in humans. First, we used Technetium-99 (a radiolabeled tracer) and methylene blue (a laboratory-made dye) to visualize olfactory deposition. Both tracers showed successful deposition. In a separate study, we used functional MRI (fMRI), to compare our LFE method with a conventional nasal spray while delivering insulin. From the fMRI results, we qualitatively observed focal decreases in brain activity in prefrontal cortex following insulin delivery. Overall, these preliminary results suggest that LFE offers a targeted approach to olfactory drug delivery, opening opportunities for access to the brain.Clinical and Translational Impact Statement - Focal deposition at the olfactory cleft is a promising target for delivering medication to the brain. We present in-human tests of a laminar fluid ejection method for intranasal drug delivery and demonstrate improvements over conventional nasal spray., (© 2024 The Authors.)

Herpes simplex virus type 1 (HSV-1) primarily targets the oral and nasal epithelia before establishing latency in the trigeminal ganglion (TG) and other peripheral ganglia. HSV-1 can also infect and become latent in the central nervous system (CNS) independent of latency in the TGs. Recent studies suggest entry to the CNS via two distinct routes: the TG-brainstem connection and olfactory nerve; however, to date, there is no characterization of brain regions targeted during HSV-1 primary infection. Furthermore, the immune response by microglia may also contribute to the heterogeneity between different brain regions. However, the response to HSV-1 by microglia has not been characterized in a region-specific manner. This study investigated the time course of HSV-1 spread within the olfactory epithelium (OE) and CNS following intranasal inoculation and the corresponding macrophage/microglial response in a C57BL/6 mouse model. We found an apical to basal spread of HSV-1 within the OE and underlying tissue accompanied by an inflammatory response of macrophages. OE infection was followed by infection of a small subset of brain regions targeted by the TG in the brainstem and other cranial nerve nuclei, including the vagus and hypoglossal nerve. Furthermore, other brain regions were positive for HSV-1 antigens, such as the locus coeruleus (LC), raphe nucleus (RaN), and hypothalamus while sparing the hippocampus and cortex. Within each brain region, microglia activation also varied widely. These findings provide critical insights into the region-specific dissemination of HSV-1 within the CNS, elucidating potential mechanisms linking viral infection to neurological and neurodegenerative diseases.IMPORTANCEThis study shows how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveal the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigens. Previous reports have identified specific brain regions found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the brain regions consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases., Competing Interests: The authors declare no conflict of interest.

Conserved protein-coding sequences are critical for maintaining protein function across species. Odorant receptors (ORs), a large poorly understood multigene family responsible for odor detection, lack comprehensive classification methods that reflect their functional diversity. In this study, we propose a new approach called conserved motif-based classification (CMC) for classifying ORs based on amino acid sequence similarities within conserved motifs. Specifically, we focused on three well-conserved motifs: MAYDRYVAIC in TM3, KAFSTCASH in TM6, and PMLNPFIY in TM7. Using an unsupervised clustering technique, we classified human ORs (hORs) into two main clusters with six sub-clusters. CMC partly reflects previously identified subfamilies, revealing altered residue positions among the sub-clusters. These altered positions interacted with specific residues within or adjacent to the transmembrane domain, suggesting functional implications. Furthermore, we found that the CMC correlated with both ligand responses and ectopic expression patterns, highlighting its relevance to OR function. This conserved motif-based classification will help in understanding the functions and features that are not understood by classification based solely on entire amino acid sequence similarity., (© 2024. The Author(s).)

Objective: To investigate the platelet-rich plasma (PRP) effectiveness in patients with a long-lasting postviral olfactory dysfunction (LPOD)., Methods: Forty-three consecutive patients with a long-lasting postviral OD were prospectively recruited. The injection of 1 mL of PRP was carried out in both olfactory clefts. The pre- to 6-month post-PRP injection change in olfaction was assessed with the olfactory disorder questionnaire (ODQ) and the threshold, discrimination, and identification (TDI) tests., Results: Forty-three patients received bilateral PRP injections (24 females). The mean age of patients was 58.9 ± 16.8 years. The mean duration of LPOD was 8.7 years. The pre to 6-month post-injection mean TDI significantly improved from 10.3 ± 10.2 to 20.12 ± 12.07 (p = 0.001). The mean ODQ significantly decreased from 29.8 ± 13.0 to 23.4 ± 11.3 (p = 0.013). The average change of the TDI and the ODQ were 9.8 and 6.4, respectively. Age was inversely associated with the 6-month threshold score., Conclusion: PRP appears to be a promising therapeutic strategy for long-lasting postviral OD. Our findings support the conduction of controlled randomized trial in this population of patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Animals have evolved innate responses to cues including social, food, and predator odors. In the natural environment, animals are faced with choices that involve balancing risk and reward where innate significance may be at odds with internal need. The ability to update the value of a cue through learning is essential for navigating changing and uncertain environments. However, the mechanisms involved in this modulation are not well defined in mammals. We have established a new olfactory assay that challenges a thirsty mouse to choose an aversive odor over an attractive odor in foraging for water, thus overriding their innate behavioral response to odor. Innately, mice prefer the attractive odor port over the aversive odor port. However, decreasing the probability of water at the attractive port leads mice to prefer the aversive port, reflecting a learned override of the innate response to the odors. The orbitofrontal cortex (OFC) is a fourth-order olfactory brain area, involved in flexible value association, with behaviorally relevant outputs throughout the limbic system. We performed optogenetic and chemogenetic silencing experiments that demonstrate the OFC is necessary for this learned modulation of innate aversion to odor. Further, we characterized odor evoked c-fos expression in learned and control mice and found significant suppression of activity in the bed nucleus of the stria terminalis, lateral septum, and central and medial amygdala. These findings reveal that the OFC is necessary for the learned override of innate behavior and may signal to limbic structures to modulate innate response to odor., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Miyamoto et al.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

"An elephant never forgets" is a popular phrase that refers not only to the elephant's extraordinary ability to remember migration routes but also to its pronounced social long-term memory (SLTM). Previous studies have shown intra- and interspecies SLTM performance, but the ability of elephants to have memories of individual humans has not yet been investigated. We tested this interspecific SLTM using auditory, olfactory, and visual stimuli, each from familiar and unfamiliar persons, in two African savanna elephant (Loxodonta africana) cows living in a zoo. The two-choice object tests revealed a higher interest in sensory stimuli from familiar keepers they had not seen for 13 years than in unfamiliar people. Statistically significant differences were found for olfactory stimuli. In addition, there was significantly more interest in visual stimuli from current keepers than in stimuli from unfamiliar people. Contrary to the results of a previous study with elephants, this was not observed for olfactory stimuli. Due to the small sample size and magnitude of the influencing factors, that is, outdoor experiment, only spatial separation of the animals, these results only represent indications of the possible interspecific SLTM. Nevertheless, we were able to provide the first empirical evidence that L. africana stores information about specific people over a long period of time. Further studies with larger sample sizes, cross-modal testing, and people disliked by the elephants could provide more insights., (© 2024 The Author(s). Zoo Biology published by Wiley Periodicals LLC.)