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ELife Sep 2023How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in , multiple compartments of the mushroom body act in...
How memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in , multiple compartments of the mushroom body act in parallel to assign a valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After formation of appetitive memory, UpWiNs acquire enhanced response to reward-predicting odors as the response of the inhibitory presynaptic MBON undergoes depression. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was terminated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains.
Topics: Animals; Wind; Learning; Drosophila; Smell; Neurons; Mushroom Bodies; Drosophila melanogaster
PubMed: 37721371
DOI: 10.7554/eLife.85756 -
Frontiers in Chemistry 2023The development of disease screening methods using biomedical detection dogs relies on the collection and analysis of body odors, particularly volatile organic compounds... (Review)
Review
The development of disease screening methods using biomedical detection dogs relies on the collection and analysis of body odors, particularly volatile organic compounds (VOCs) present in body fluids. To capture and analyze odors produced by the human body, numerous protocols and materials are used in forensics or medical studies. This paper provides an overview of sampling devices used to collect VOCs from sweat and exhaled air, for medical diagnostic purposes using canine olfaction and/or Gas Chromatography-Mass spectrometry (GC-MS). Canine olfaction and GC-MS are regarded as complementary tools, holding immense promise for detecting cancers and infectious diseases. However, existing literature lacks guidelines for selecting materials suitable for both canine olfaction and GC-MS. Hence, this review aims to address this gap and pave the way for efficient body odor sampling materials. The first section of the paper describes the materials utilized in training sniffing dogs, while the second section delves into the details of sampling devices and extraction techniques employed for exhaled air and sweat analysis using GC-MS. Finally, the paper proposes the development of an ideal sampling device tailored for detection purposes in the field of odorology. By bridging the knowledge gap, this study seeks to advance disease detection methodologies, harnessing the unique abilities of both dogs and GC-MS analysis in biomedical research.
PubMed: 38025078
DOI: 10.3389/fchem.2023.1282450 -
Nature Communications Dec 2023Structural and mechanistic studies on human odorant receptors (ORs), key in olfactory signaling, are challenging because of their low surface expression in heterologous...
Structural and mechanistic studies on human odorant receptors (ORs), key in olfactory signaling, are challenging because of their low surface expression in heterologous cells. The recent structure of OR51E2 bound to propionate provided molecular insight into odorant recognition, but the lack of an inactive OR structure limited understanding of the activation mechanism of ORs upon odorant binding. Here, we determined the cryo-electron microscopy structures of consensus OR52 (OR52), a representative of the OR52 family, in the ligand-free (apo) and octanoate-bound states. The apo structure of OR52 reveals a large opening between transmembrane helices (TMs) 5 and 6. A comparison between the apo and active structures of OR52 demonstrates the inward and outward movements of the extracellular and intracellular segments of TM6, respectively. These results, combined with molecular dynamics simulations and signaling assays, shed light on the molecular mechanisms of odorant binding and activation of the OR52 family.
Topics: Humans; Odorants; Receptors, Odorant; Cryoelectron Microscopy; Smell; Molecular Dynamics Simulation; Neoplasm Proteins
PubMed: 38062020
DOI: 10.1038/s41467-023-43983-9 -
Biology Letters Jan 2024
Topics: Animals; Insecta; Flight, Animal
PubMed: 38263881
DOI: 10.1098/rsbl.2023.0565 -
Brain Sciences Jan 2024Long-COVID mercilessly brought awareness to what olfaction researchers have known all along; losing your sense of smell changes your experiences with the world around...
Long-COVID mercilessly brought awareness to what olfaction researchers have known all along; losing your sense of smell changes your experiences with the world around you and can compromise your health and wellbeing [...].
PubMed: 38391717
DOI: 10.3390/brainsci14020142 -
International Journal of Molecular... Mar 2024There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological... (Review)
Review
There is very little knowledge regarding the terminal nerve, from its implications in the involvement and pathogenesis of certain conditions, to its embryological origin. With this review, we try to summarize the most important evidence on the terminal nerve, aiming to clarify its anatomy and the various functions attributed to it, to better interpret its potential involvement in pathological processes. Recent studies have also suggested its potential role in the control of human reproductive functions and behaviors. It has been hypothesized that it plays a role in the unconscious perception of specific odors that influence autonomic and reproductive hormonal systems through the hypothalamic-pituitary-gonadal axis. We used the PubMed database and found different articles which were then selected independently by three authors. We found 166 articles, of which, after careful selection, only 21 were analyzed. The terminal nerve was always thought to be unimportant in our body. It was well studied in different types of animals, but few studies have been completed in humans. For this reason, its function remains unknown. Studies suggest a possible implication in olfaction due to the anatomical proximity with the olfactive nerve. Others suggest a more important role in reproduction and sexual behaviors. New emerging information suggests a possible role in Kallmann syndrome and COVID-19.
Topics: Animals; Humans; Smell; Kallmann Syndrome; Nerve Endings; Autonomic Nervous System; COVID-19
PubMed: 38612730
DOI: 10.3390/ijms25073920 -
MedRxiv : the Preprint Server For... Oct 2023Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse.
BACKGROUND
Olfactory impairment is common in older adults and may be associated with adverse cardiovascular health; however, empirical evidence is sparse.
OBJECTIVE
To examine olfaction and the risk of coronary heart disease (CHD), stroke, and congestive heart failure (CHF).
METHODS
This study included 2,537 older adults (aged 75.6±2.8 years) from the Health ABC Study with olfaction assessed by the 12-item Brief Smell Identification Test in 1999-2000, defined as poor (score ≤8), moderate (9-10), or good (11-12). The outcomes were incident CHD, stroke, and CHF.
RESULTS
During up to 12-year follow-up, 353 incident CHD, 258 stroke, and 477 CHF events were identified. Olfaction was associated with incident CHF, but not with CHD or stroke. After adjusting for demographics, the cause-specific hazard ratio (HR) of CHF was 1.35 (95% confidence interval (CI): 1.08, 1.70) for moderate and 1.39 (95%CI: 1.09, 1.76) for poor olfaction. With additional adjustment for lifestyle, chronic diseases, and biomarkers of CHF, the HR was modestly attenuated to 1.32 (95%CI: 1.05, 1.66) for moderate and 1.28 (95%CI: 1.01, 1.64) for poor olfaction. These associations were robust in pre-planned subgroup analyses by age, sex, race, and prevalent CHD/stroke. However, the associations appeared to be evident among participants who reported very-good-to-excellent health (HR=1.47 (95%CI: 1.02, 2.13) for moderate and 1.76, (95%CI: 1.20, 2.57) for poor olfaction). In contrast, null association with CHF was found among those with fair-to-poor self-reported health.
CONCLUSIONS
In community-dwelling older adults, a single olfaction test was associated with a long-term risk for incident CHF, particularly among those reporting very-good-to-excellent health.
PubMed: 37961698
DOI: 10.1101/2023.10.27.23297697 -
The Journals of Gerontology. Series A,... Jul 2023Olfactory impairment is increasingly recognized as a biomarker of frailty, but the relationship between olfactory subdomains that describe peripheral or central...
BACKGROUND
Olfactory impairment is increasingly recognized as a biomarker of frailty, but the relationship between olfactory subdomains that describe peripheral or central dysfunction and frailty remains unexplored.
METHODS
We examined 1 160 older adults from the National Social Life, Health, and Aging Project Wave 3. Olfactory identification (OI): the ability to identify an odorant; and olfactory sensitivity (OS): the ability to detect the presence of an odorant, were assessed using 5- and 6-point measures, respectively. Frailty was operationalized as both a 37-item frailty index (FI) and the 5-item Physical Frailty Phenotype (PFP). Mixed models were fit to examine the association between OI, OS, FI, and PFP, while adjusting for demographic and clinical covariates.
RESULTS
Participants in the most-frail PFP category had lower OI and OS scores (OI: 3.88 vs 4.19, p = .016; OS: 3.15 vs 3.47, p = .031), whereas participants in the most-frail FI category exhibited lower OI scores but not OS scores when compared to nonfrail participants (OI: 3.72 vs 4.27, p = .014; OS: 3.19 vs 3.43, p = .476). Adjusted mixed models showed that a point increase in OI was associated with a lower PFP score (β = -0.107, p = .006) and FI score (β = -0.009, p = .010). A point increase in OS was associated with a lower PFP score (β = -0.058, p = .016) but not FI score (β = -0.004, p = .064).
CONCLUSION
Both OS and OI, predominantly peripheral and central measures of olfaction, respectively, are associated with frailty implicating olfaction as a potential biomarker and risk factor for frailty.
Topics: Humans; Aged; Frailty; Smell; Risk Factors; Aging; Olfaction Disorders; Frail Elderly; Geriatric Assessment
PubMed: 36502375
DOI: 10.1093/gerona/glac237