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1.
ACS Chem Neurosci ; 13(12): 1727-1737, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35642309

RESUMO

Inspired by the powerful capability of the biological olfactory system, we developed an in vivo bioelectronic nose based on a bioengineered rat by recording electrophysiological-responsive signals from the olfactory bulb with implanted multichannel microelectrodes. The bioengineered rat was prepared by overexpressing a selected olfactory receptor (OR3) on the rat olfactory epithelium, and multichannel electrophysiological signals were obtained from the mitral/tufted (M/T) cell population of the olfactory bulb. The classification of target multiodorants was realized by analyzing the redundant stimuli-responsive firing information. Ligand odorants induced significant firing changes with specific response patterns compared with nonligand odorants. The responsive curves were dependent on the concentration of target ligand odorants ranging from 10-6 to 10-3 M, and the detection limit was as low as 10-5 M. In addition, different ligand odorants were successfully discriminated via principal component analysis. This in vivo bioelectronic nose provides a novel approach for the detection of specific target odorants and has promising application potential in the field of rapid on-site odor discrimination.


Assuntos
Bulbo Olfatório , Olfato , Animais , Ligantes , Microeletrodos , Odorantes/análise , Ratos , Olfato/fisiologia
2.
Elife ; 112022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35708179

RESUMO

Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1- or D2-type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.


Assuntos
Sinais (Psicologia) , Estriado Ventral , Animais , Camundongos , Neurônios/fisiologia , Odorantes , Tubérculo Olfatório/fisiologia , Receptores de Dopamina D2/metabolismo , Olfato/fisiologia , Estriado Ventral/metabolismo
3.
Nature ; 606(7914): 550-556, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35545672

RESUMO

Animals constantly receive various sensory stimuli, such as odours, sounds, light and touch, from the surrounding environment. These sensory inputs are essential for animals to search for food and avoid predators, but they also affect their physiological status, and may cause diseases such as cancer. Malignant gliomas-the most lethal form of brain tumour1-are known to intimately communicate with neurons at the cellular level2,3. However, it remains unclear whether external sensory stimuli can directly affect the development of malignant glioma under normal living conditions. Here we show that olfaction can directly regulate gliomagenesis. In an autochthonous mouse model that recapitulates adult gliomagenesis4-6 originating in oligodendrocyte precursor cells (OPCs), gliomas preferentially emerge in the olfactory bulb-the first relay of brain olfactory circuitry. Manipulating the activity of olfactory receptor neurons (ORNs) affects the development of glioma. Mechanistically, olfaction excites mitral and tufted (M/T) cells, which receive sensory information from ORNs and release insulin-like growth factor 1 (IGF1) in an activity-dependent manner. Specific knockout of Igf1 in M/T cells suppresses gliomagenesis. In addition, knocking out the IGF1 receptor in pre-cancerous mutant OPCs abolishes the ORN-activity-dependent mitogenic effects. Our findings establish a link between sensory experience and gliomagenesis through their corresponding sensory neuronal circuits.


Assuntos
Neurônios Receptores Olfatórios , Olfato , Animais , Fator de Crescimento Insulin-Like I , Camundongos , Bulbo Olfatório/fisiologia , Células Receptoras Sensoriais , Olfato/fisiologia
4.
Chem Senses ; 472022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35522082

RESUMO

The sense of smell employs some of the largest gene families in the genome to detect and distinguish a multitude of different odors. Within vertebrates, 4 major olfactory receptor families have been described; of which, only 3 (OR, TAAR-like, and V1R) were found already in lamprey, a jawless vertebrate. The forth family (V2R) was believed to have originated later, in jawed vertebrates. Here we have delineated the entire vomeronasal receptor repertoire in 3 lamprey species. We report the presence of 6 v1r and 2 v2r genes in Lethenteron camtschaticum, arctic lamprey, and Lampetra fluviatilis, river lamprey (6 and 1, respectively, in sea lamprey, Petromyzon marinus). Three v1r genes but no v2r genes were found to be expressed in olfactory sensory neurons in the characteristic sparse expression pattern. Our results show the olfactory function of some V1Rs already in lamprey and, unexpectedly, an early origin of the V2R family in the shared ancestor of jawed and jawless vertebrates. However, lamprey v2r genes appear not to have acquired an olfactory function yet, thus dissociating the evolutionary origin of the family from the onset of a function as olfactory receptor.


Assuntos
Neurônios Receptores Olfatórios , Petromyzon , Receptores Odorantes , Órgão Vomeronasal , Animais , Petromyzon/genética , Filogenia , Receptores Odorantes/genética , Olfato/fisiologia , Vertebrados/genética
5.
Chem Senses ; 472022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35588293

RESUMO

Emotions can be communicated in social contexts through chemosignals contained in human body odors. The transmission of positive emotions via these signals has received little interest in past research focused mainly on negative emotional transmission. Furthermore, how the use of perfumed products might modulate this transmission remains poorly understood. To investigate human positive chemical communication, we explored the autonomic, verbal, and behavioral responses of receivers exposed to body odors of donors having undergone a within-subject positive or neutral mood induction procedure. These responses were compared with those obtained after exposure to the same body odors with added fragrance. Our findings suggest that positive emotions can be transmitted through body odor. They not only induced modifications at the physiological (heart rate) and verbal levels (perceived intensity and familiarity) but also at the behavioral level, with an improved performance on creativity tasks. Perfume did not modulate the physiological effects and had a synergistic effect on the positive body odor ratings (increased perceived differences between the neutral and positive body odor).


Assuntos
Perfumes , Emoções/fisiologia , Humanos , Odorantes , Olfato/fisiologia , Suor
6.
Sci Rep ; 12(1): 8506, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35595846

RESUMO

Thanks to its well-known neuroanatomy, limited brain size, complex behaviour, and the extensive genetic methods, Drosophila has become an indispensable model in neuroscience. A vast number of studies have focused on its olfactory system and the processing of odour information. Optogenetics is one of the recently developed genetic tools that significantly advance this field of research, allowing to replace odour stimuli by direct neuronal activation with light. This becomes a universal all-optical toolkit when spatially selective optogenetic activation is combined with calcium imaging to read out neuronal responses. Initial experiments showed a successful implementation to study the olfactory system in fish and mice, but the olfactory system of Drosophila has been so far precluded from an application. To fill this gap, we present here optogenetic tools to selectively stimulate functional units in the Drosophila olfactory system, combined with two-photon calcium imaging to read out the activity patterns elicited by these stimuli at different levels of the brain. This method allows to study the spatial and temporal features of the information flow and reveals the functional connectivity in the olfactory network.


Assuntos
Cálcio , Drosophila , Animais , Camundongos , Odorantes , Optogenética/métodos , Olfato/fisiologia
7.
JAMA Neurol ; 79(6): 544-553, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35404378

RESUMO

Importance: Loss of smell is an early and common presentation of COVID-19 infection. Although it has been speculated that viral infection of olfactory neurons may be the culprit, it is unclear whether viral infection causes injuries in the olfactory bulb region. Objective: To characterize the olfactory pathology associated with COVID-19 infection in a postmortem study. Design, Setting, and Participants: This multicenter postmortem cohort study was conducted from April 7, 2020, to September 11, 2021. Deceased patients with COVID-19 and control individuals were included in the cohort. One infant with congenital anomalies was excluded. Olfactory bulb and tract tissue was collected from deceased patients with COVID-19 and appropriate controls. Histopathology, electron microscopy, droplet digital polymerase chain reaction, and immunofluorescence/immunohistochemistry studies were performed. Data analysis was conducted from February 7 to October 19, 2021. Main Outcomes and Measures: (1) Severity of degeneration, (2) losses of olfactory axons, and (3) severity of microvasculopathy in olfactory tissue. Results: Olfactory tissue from 23 deceased patients with COVID-19 (median [IQR] age, 62 [49-69] years; 14 men [60.9%]) and 14 control individuals (median [IQR] age, 53.5 [33.25-65] years; 7 men [50%]) was included in the analysis. The mean (SD) axon pathology score (range, 1-3) was 1.921 (0.569) in patients with COVID-19 and 1.198 (0.208) in controls (P < .001), whereas axon density was 2.973 (0.963) × 104/mm2 in patients with COVID-19 and 3.867 (0.670) × 104/mm2 in controls (P = .002). Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean (SD) microvasculopathy score (range, 1-3) was 1.907 (0.490) in patients with COVID-19 and 1.405 (0.233) in control individuals (P < .001). Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean [SD] axon pathology score, 2.260 [0.457] vs 1.63 [0.426]; P = .002; mean [SD] microvasculopathy score, 2.154 [0.528] vs 1.694 [0.329]; P = .02) but was not associated with clinical severity, timing of infection, or presence of virus. Conclusions and Relevance: This study found that COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue. The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent.


Assuntos
COVID-19 , Transtornos do Olfato , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , SARS-CoV-2 , Olfato/fisiologia
8.
BMC Ecol Evol ; 22(1): 50, 2022 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429979

RESUMO

BACKGROUND: Insects have exceptionally fast smelling capabilities, and some can track the temporal structure of odour plumes at rates above 100 Hz. It has been hypothesized that this fast smelling capability is an adaptation for flying. We test this hypothesis by comparing the olfactory acuity of sympatric flighted versus flightless lineages within a wing-polymorphic stonefly species. RESULTS: Our analyses of olfactory receptor neuron responses reveal that recently-evolved flightless lineages have reduced olfactory acuity. By comparing flighted versus flightless ecotypes with similar genetic backgrounds, we eliminate other confounding factors that might have affected the evolution of their olfactory reception mechanisms. Our detection of different patterns of reduced olfactory response strength and speed in independently wing-reduced lineages suggests parallel evolution of reduced olfactory acuity. CONCLUSIONS: These reductions in olfactory acuity echo the rapid reduction of wings themselves, and represent an olfactory parallel to the convergent phenotypic shifts seen under selective gradients in other sensory systems (e.g. parallel loss of vision in cave fauna). Our study provides evidence for the hypothesis that flight poses a selective pressure on the speed and strength of olfactory receptor neuron responses and emphasizes the energetic costs of rapid olfaction.


Assuntos
Insetos , Asas de Animais , Animais , Cavernas , Ecótipo , Insetos/genética , Olfato/fisiologia , Asas de Animais/fisiologia
9.
Curr Opin Neurobiol ; 73: 102528, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35367860

RESUMO

Animals recognize groups and mixtures of odors as a unitary object. This ability is crucial to generalize known odors to newly encountered ones despite variations. However, it remains largely unknown how multitudes of odors are represented and organized in the higher brain regions to support odor object recognition. Here we discuss recent advances uncovering the population odor responses in the rodent piriform cortex and the Drosophila mushroom body, and highlight the emerging principles on the organization, mechanism, stereotypy, and experience-dependence of central odor representations.


Assuntos
Odorantes , Córtex Piriforme , Animais , Drosophila , Corpos Pedunculados/fisiologia , Condutos Olfatórios/fisiologia , Córtex Piriforme/fisiologia , Olfato/fisiologia
10.
Front Neural Circuits ; 16: 861800, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431818

RESUMO

In the mouse olfactory system, odor signals detected in the olfactory epithelium are converted to a topographic map of activated glomeruli in the olfactory bulb. The map information is then conveyed by projection neurons, mitral cells and tufted cells, to various areas in the olfactory cortex. An odor map is transmitted to the anterior olfactory nucleus by tufted cells for odor identification and recollection of associated memory for learned decisions. For instinct decisions, odor information is directly transmitted to the valence regions in the amygdala by specific subsets of mitral cells. Transmission of orthonasal odor signals through these two distinct pathways, innate and learned, are closely related with exhalation and inhalation, respectively. Furthermore, the retronasal/interoceptive and orthonasal/exteroceptive signals are differentially processed during the respiratory cycle, suggesting that these signals are processed in separate areas of the olfactory bulb and olfactory cortex. In this review article, the recent progress is summarized for our understanding of the olfactory circuitry and processing of odor signals during respiration.


Assuntos
Odorantes , Bulbo Olfatório , Tonsila do Cerebelo , Animais , Camundongos , Condutos Olfatórios/fisiologia , Respiração , Olfato/fisiologia
11.
Biochem Biophys Res Commun ; 609: 156-162, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35430419

RESUMO

The insect repellent methyl salicylate elicits excitatory responses upon interaction with CquiOR32, an odorant receptor (OR) from the southern house mosquito, Culex quinquefasciatus. By contrast, eucalyptol binds to CquiOR32 to generate electrophysiological and behavioral inhibitory responses. In an attempt to identify CquiOR32 variants displaying more robust inhibitory responses for more accurate current-voltage analysis, we sequenced 31 CquiOR32 clones. In the Xenopus oocyte recording system, CquiOR32V2/CquiOrco-expressing oocytes yielded eucalyptol-elicited outward (inhibitory) currents relatively larger than methyl salicylate-generated inward (excitatory) currents. Rescuing experiments showed that two of the amino acid substitutions in CquiOR32V2 located in a predicted transmembrane helix of the receptor are determinants of the outward/inward ratios. These findings, along with co-stimulus assays, suggest that odorant and inhibitor may bind to the same binding pocket. Current-voltage relationships obtained with standard perfusion buffer and those devoid of Na+ or Cl- indicated that both excitatory and inhibitory currents are mediated, at least in part, by cation. We then concluded that eucalyptol is an inverse agonist, which shifts the open ⇔ closed equilibrium of the receptor toward the closed conformation, thus reducing the spontaneous activity. By contrast, the binding of methyl salicylate shifts the equilibrium towards the open conformation and, consequently, leads to an increase in cation influx.


Assuntos
Culicidae , Receptores Odorantes , Animais , Eucaliptol/farmacologia , Odorantes , Receptores Odorantes/metabolismo , Olfato/fisiologia
12.
Neurobiol Aging ; 114: 73-83, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35413485

RESUMO

Normal brain aging is associated with deficits in cognitive and sensory processes, due to subtle impairment of synaptic contacts and plasticity. Impairment may be discrete in basal conditions but is revealed when cerebral plasticity is involved, such as in learning contexts. We used olfactory perceptual learning, a non-associative form of learning in which discrimination between perceptually similar odorants is improved following exposure to these odorants, to better understand the cellular bases of olfactory aging in mice. We first evaluated learning ability and memory retention in 2-, 6-, 12-, and 18-month-old mice, and identified 12 months as a pivotal age when memory retention subtly declines before learning becomes totally impaired at later ages. We then showed that learning-induced structural plasticity of adult-born granule cells is specific to cells responding to the learned odorants in the olfactory bulb of young adult mice and loses its specificity in 12-month-old mice, in parallel to memory impairment. Taken together, our data refine our understanding of aging-related impairment of plasticity mechanisms in the olfactory bulb and consequent induction of olfactory learning and memory deficits.


Assuntos
Neurogênese , Bulbo Olfatório , Envelhecimento/fisiologia , Animais , Transtornos da Memória , Camundongos , Neurogênese/fisiologia , Plasticidade Neuronal/fisiologia , Odorantes , Bulbo Olfatório/fisiologia , Olfato/fisiologia
13.
Chem Senses ; 472022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35427412

RESUMO

Olfaction is functional at birth and newborns use their sense of smell to navigate their environment. Yet, certain chemosensory abilities are subject to experience and develop with age. It has been argued that odor discrimination is a key ability enabling organisms to capture and distinguish odors occurring in the environment to further identify them and formulate a behavioral response. Yet, the development of odor discrimination abilities has been overlooked in the literature, with few attempts to investigate developmental changes in odor discrimination abilities independent of verbal abilities and olfactory experience. Here, building on these attempts, we propose a novel approach to studying the development of odor discrimination abilities by utilizing odor enantiomersâpairs of odorous molecules of identical chemical and physical features, but differing in optical activity. We hypothesized that discrimination of enantiomeric odor pairs in children and adolescents would be less prone to age effects than discrimination of pairs of common odors due to their encoding difficulty and their limited exposure in common olfactory experience. We examined olfactory discrimination abilities in children aged 4â12 years with regard to three common odor pairs and five enantiomeric odor pairs. The study protocol eliminated verbal and cognitive development bias, resulting in diminished age advantage of the older children in discrimination of enantiomers as compared to common odors.


Assuntos
Odorantes , Olfato , Adolescente , Criança , Humanos , Recém-Nascido , Olfato/fisiologia
14.
J Neurosci ; 42(21): 4278-4296, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35440491

RESUMO

Odors are transported by turbulent air currents, creating complex temporal fluctuations in odor concentration that provide a potentially informative stimulus dimension. We have shown that mice are able to discriminate odor stimuli based on their temporal structure, indicating that information contained in the temporal structure of odor plumes can be extracted by the mouse olfactory system. Here, using in vivo extracellular and intracellular electrophysiological recordings, we show that mitral cells (MCs) and tufted cells (TCs) of the male C57BL/6 mouse olfactory bulb can encode the dominant temporal frequencies present in odor stimuli up to at least 20 Hz. A substantial population of cell-odor pairs showed significant coupling of their subthreshold membrane potential with the odor stimulus at both 2 Hz (29/70) and the suprasniff frequency 20 Hz (24/70). Furthermore, mitral/tufted cells (M/TCs) show differential coupling of their membrane potential to odor concentration fluctuations with tufted cells coupling more strongly for the 20 Hz stimulation. Frequency coupling was always observed to be invariant to odor identity, and M/TCs that coupled well to a mixture also coupled to at least one of the components of the mixture. Interestingly, pharmacological blocking of the inhibitory circuitry strongly modulated frequency coupling of cell-odor pairs at both 2 Hz (10/15) and 20 Hz (9/15). These results provide insight into how both cellular and circuit properties contribute to the encoding of temporal odor features in the mouse olfactory bulb.SIGNIFICANCE STATEMENT Odors in the natural environment have a strong temporal structure that can be extracted and used by mice in their behavior. Here, using in vivo extracellular and intracellular electrophysiological techniques, we show that the projection neurons in the olfactory bulb can encode and couple to the dominant frequency present in an odor stimulus. Furthermore, frequency coupling was observed to be differential between mitral and tufted cells and was odor invariant but strongly modulated by local inhibitory circuits. In summary, this study provides insight into how both cellular and circuit properties modulate encoding of odor temporal features in the mouse olfactory bulb.


Assuntos
Odorantes , Bulbo Olfatório , Animais , Interneurônios , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Bulbo Olfatório/fisiologia , Olfato/fisiologia
15.
Support Care Cancer ; 30(7): 6155-6162, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35426047

RESUMO

PURPOSE: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10. RESULTS: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. CONCLUSION: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.


Assuntos
Ageusia , Neoplasias do Sistema Nervoso Central , Neoplasias Cerebelares , Meduloblastoma , Neoplasias Embrionárias de Células Germinativas , Transtornos do Olfato , Anosmia , Estudos Transversais , Humanos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Olfato/fisiologia , Sobreviventes , Paladar/fisiologia
16.
Medicina (Kaunas) ; 58(3)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35334524

RESUMO

Background and Objectives: Since the COVID-19 pandemic, the number of cases of post-infectious olfactory dysfunction (PIOD) has substantially increased. Despite a good recovery rate, olfactory dysfunction (OD) becomes persistent in up to 15% of cases and further research is needed to find new treatment modalities for those patients who have not improved on currently available treatments. Social media has emerged as a potential avenue for patient recruitment, but its role in recruiting patients with smell dysfunction remains unexplored. We conducted a survey using the AbScent Facebook page to evaluate the feasibility of using this platform for future studies on smell dysfunction. Materials and Methods: Between 26 October and 4 November 2021, we conducted an online survey to evaluate propensity of patients with PIOD who would be willing to participate in research studies on smell dysfunction. Results: Sixty-five subjects were surveyed with a response rate of 90.7%. The median visual analogue scale (VAS) for sense of smell was 0 at infection and 2 at survey completion. The median length of OD was 1.6 years, and the main cause of OD was SARS-CoV-2 (57.6%). Parosmia was reported in 41 subjects (69.5%) whilst phantosmia in 22 (37.3%). The median length of olfactory training (OT) was 6 months but subjectively effective in 15 subjects (25.4%). Twenty-seven subjects (45.8%) tried other medications to improve olfaction, but only 6 participants (22.2%) reported an improvement. All subjects expressed their propensity to participate in future studies with most of them (38; 64.4%) willing to be enrolled either in medical and surgical studies or to be part of a randomised study design (11; 18.6%). Conclusions: Using the AbScent Facebook platform we successfully selected a population of subjects with persistent and severe OD that have failed to improve on available treatments and are willing to participate in further clinical trials.


Assuntos
COVID-19 , Transtornos do Olfato , Mídias Sociais , COVID-19/complicações , Humanos , Transtornos do Olfato/etiologia , Pandemias , Seleção de Pacientes , SARS-CoV-2 , Olfato/fisiologia
17.
Nutrients ; 14(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35334919

RESUMO

Smell plays a critical role in food choice and intake by influencing energy balance and body weight. Malnutrition problems or modified eating behaviors have been associated with olfactory impairment or loss. The obesity epidemic is a serious health problem associated with an increased risk of mortality and major physical comorbidities. The etiopathogenesis of obesity is complex and multifactorial, and one of the main factors contributing to the rapid increase in its incidence is the environment in which we live, which encourages the overconsumption of foods rich in energy, such as saturated fats and sugars. By means of the "Sniffin' Sticks" test, we measured the olfactory threshold, discrimination and identification score (TDI score) in patients of the Obesity Center of the University Hospital (OC; n = 70) and we compared them with that of healthy normal weight controls (HC; n = 65). OC patients demonstrated a significantly lower olfactory function than HC subjects both general and specific for the ability to discriminate and identify odors, even when they were considered separately as females and males. For OC patients, a negative correlation was found between body mass index (BMI) and olfactory scores obtained by each subject, both when they were divided according to gender and when they were considered all together. Besides, normosmic OC patients showed a significantly lower BMI than hyposmic ones. A reduced sense of smell may contribute to obesity involving the responses of the cephalic phase, with a delay in the achievement of satiety and an excessive intake of high-energy foods and drinks.


Assuntos
Sobrepeso , Olfato , Índice de Massa Corporal , Feminino , Voluntários Saudáveis , Humanos , Masculino , Obesidade/complicações , Sobrepeso/complicações , Olfato/fisiologia
18.
Proc Natl Acad Sci U S A ; 119(10): e2120093119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35238656

RESUMO

SignificanceThe authors propose that odors are consciously perceived or not, depending on whether the olfactory cortex succeeds in activating the endopiriform nucleus-a structure that, in turn, is capable of activating multiple downstream brain areas. The authors further propose that the cellular mechanisms of endopiriform nucleus activation are an attenuated form of cellular events that occur during epileptic seizure initiation. If correct, the authors' hypothesis could help explain the mechanisms of action of certain general anesthetics.


Assuntos
Potenciais Evocados , Olfato/fisiologia , Animais , Córtex Piriforme/metabolismo , Córtex Piriforme/fisiologia , Convulsões/fisiopatologia , Transdução de Sinais , Sódio/metabolismo
19.
Elife ; 112022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35254262

RESUMO

Sensory systems are often tasked to analyse complex signals from the environment, separating relevant from irrelevant parts. This process of decomposing signals is challenging when a mixture of signals does not equal the sum of its parts, leading to an unpredictable corruption of signal patterns. In olfaction, nonlinear summation is prevalent at various stages of sensory processing. Here, we investigate how the olfactory system deals with binary mixtures of odours under different brain states by two-photon imaging of olfactory bulb (OB) output neurons. Unlike previous studies using anaesthetised animals, we found that mixture summation is more linear in the early phase of evoked responses in awake, head-fixed mice performing an odour detection task, due to dampened responses. Despite smaller and more variable responses, decoding analyses indicated that the data from behaving mice was well discriminable. Curiously, the time course of decoding accuracy did not correlate strictly with the linearity of summation. Further, a comparison with naïve mice indicated that learning to accurately perform the mixture detection task is not accompanied by more linear mixture summation. Finally, using a simulation, we demonstrate that, while saturating sublinearity tends to degrade the discriminability, the extent of the impairment may depend on other factors, including pattern decorrelation. Altogether, our results demonstrate that the mixture representation in the primary olfactory area is state-dependent, but the analytical perception may not strictly correlate with linearity in summation.


Assuntos
Percepção Olfatória , Neurônios Receptores Olfatórios , Animais , Camundongos , Neurônios/fisiologia , Odorantes , Bulbo Olfatório/fisiologia , Condutos Olfatórios/fisiologia , Percepção Olfatória/fisiologia , Olfato/fisiologia
20.
Elife ; 112022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-35285796

RESUMO

Anatomical and physiological compartmentalization of neurons is a mechanism to increase the computational capacity of a circuit, and a major question is what role axonal compartmentalization plays. Axonal compartmentalization may enable localized, presynaptic plasticity to alter neuronal output in a flexible, experience-dependent manner. Here, we show that olfactory learning generates compartmentalized, bidirectional plasticity of acetylcholine release that varies across the longitudinal compartments of Drosophila mushroom body (MB) axons. The directionality of the learning-induced plasticity depends on the valence of the learning event (aversive vs. appetitive), varies linearly across proximal to distal compartments following appetitive conditioning, and correlates with learning-induced changes in downstream mushroom body output neurons (MBONs) that modulate behavioral action selection. Potentiation of acetylcholine release was dependent on the CaV2.1 calcium channel subunit cacophony. In addition, contrast between the positive conditioned stimulus and other odors required the inositol triphosphate receptor, which maintained responsivity to odors upon repeated presentations, preventing adaptation. Downstream from the MB, a set of MBONs that receive their input from the γ3 MB compartment were required for normal appetitive learning, suggesting that they represent a key node through which reward learning influences decision-making. These data demonstrate that learning drives valence-correlated, compartmentalized, bidirectional potentiation, and depression of synaptic neurotransmitter release, which rely on distinct mechanisms and are distributed across axonal compartments in a learning circuit.


Assuntos
Acetilcolina , Olfato , Animais , Axônios , Drosophila/fisiologia , Drosophila melanogaster , Corpos Pedunculados/fisiologia , Plasticidade Neuronal/fisiologia , Neurotransmissores , Olfato/fisiologia
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