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Sample records for tg2576 mouse olfactory

  1. Neuritin attenuates cognitive function impairments in tg2576 mouse model of Alzheimer's disease.

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    Yoori Choi

    Full Text Available Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.

  2. Environmental enrichment does not influence hypersynchronous network activity in the Tg2576 mouse model of Alzheimer’s disease

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    Charlotte eBezzina

    2015-09-01

    Full Text Available The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment durably improves memory performances in the Tg2576 mouse model of Alzheimer’s disease. Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after environmental enrichment were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after environmental enrichment period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and two weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic recordings. Thus, the long-lasting effect of this environmental enrichment protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages.

  3. Iron Chelation Inhibits Osteoclastic Differentiation In Vitro and in Tg2576 Mouse Model of Alzheimer's Disease.

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    Jun-Peng Guo

    Full Text Available Patients of Alzheimer's disease (AD frequently have lower bone mineral density and higher rate of hip fracture. Tg2576, a well characterized AD animal model that ubiquitously express Swedish mutant amyloid precursor protein (APPswe, displays not only AD-relevant neuropathology, but also age-dependent bone deficits. However, the underlying mechanisms remain poorly understood. As APP is implicated as a regulator of iron export, and the metal chelation is considered as a potential therapeutic strategy for AD, we examined iron chelation's effect on the osteoporotic deficit in Tg2576 mice. Remarkably, in vivo treatment with iron chelator, clinoquinol (CQ, increased both trabecular and cortical bone-mass, selectively in Tg2576, but not wild type (WT mice. Further in vitro studies showed that low concentrations of CQ as well as deferoxamine (DFO, another iron chelator, selectively inhibited osteoclast (OC differentiation, without an obvious effect on osteoblast (OB differentiation. Intriguingly, both CQ and DFO's inhibitory effect on OC was more potent in bone marrow macrophages (BMMs from Tg2576 mice than that of wild type controls. The reduction of intracellular iron levels in BMMs by CQ was also more dramatic in APPswe-expressing BMMs. Taken together, these results demonstrate a potent inhibition on OC formation and activation in APPswe-expressing BMMs by iron chelation, and reveal a potential therapeutic value of CQ in treating AD-associated osteoporotic deficits.

  4. The early changes in behavior and the myelinated fibers of the white matter in the Tg2576 transgenic mouse model of Alzheimer's disease.

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    Zhang, Lei; Lu, Wei; Chen, Lin; Qiu, Xuan; Li, Chen; Huang, Chun-Xia; Gong, Xia; Min, Qi-Cheng; Lu, Fang; Wan, Jing-Yuan; Chao, Feng-Lei; Tang, Yong

    2013-10-25

    Recently, increasing evidences have indicated that abnormal behavior and white matter changes had appeared before senile plaques were formed in Alzheimer's disease (AD). However, the exact nature of these changes in behavior and white matter structure in early AD are unclear. This study used the Morris water maze, an ELISA assay, a transmission electron microscopic technique and new stereological methods to investigate the behavior, Aβ protein expression and white matter structure of Tg2576 transgenic mice at four ages. Only 10 months of age, the time latency in the Morris water maze tasks for Tg2576 transgenic mice were significantly longer than that of wild-type mice. The concentration of Aβ40 protein in the white matter of the Tg2576 transgenic mice was significantly increased in four ages mice, but the Aβ42 protein was significantly increased only in the 6-month-old mice. In 10-month-old mice, the axon volume in the white matter of the Tg2576 transgenic mice was significantly decreased when compared to the wild-type mice. These results suggest that the deposition of Aβ in the white matter of Tg2576 transgenic mice appeared before the spatial memory decline. The early detection of the Aβ content in the white matter of AD might help diagnose suspected AD. In addition, the axon changes in the white matter of AD might be one of the morphological causes of the behavioral deficits observed in 10-month-old transgenic mouse models of AD, and protecting the axons in the white matter might be an important method for delaying the progression of AD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Age-related changes of protein SUMOylation balance in the AβPP Tg2576 mouse model of Alzheimer's disease

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    Robert eNisticò

    2014-04-01

    Full Text Available Alzheimer's disease (AD is a complex disorder that affects the central nervous system causing a severe neurodegeneration. This pathology affects an increasing number of people worldwide due to the overall aging of the human population. In recent years SUMO protein modification has emerged as a possible cellular mechanism involved in AD. Some of the proteins engaged in the physiopathological process of AD, like BACE1, GSK3-β tau, AβPP and JNK, are in fact subject to protein SUMO modifications or interactions. Here, we have investigated the SUMO/deSUMOylation balance and SUMO-related proteins during the onset and progression of the pathology in the Tg2576 mouse model of AD. We examined four age-stages (1.5; 3; 6; 17 months old and observed shows an increase in SUMO-1 protein conjugation at 3 and 6 months in transgenic mice with respect to WT in both cortex and hippocampus. Interestingly this is paralleled by increased expression levels of Ubc9 and SENP1 in both brain regions. At 6 months of age also the SUMO-1 mRNA resulted augmented. SUMO-2-ylation was surprisingly decreased in old transgenic mice and was unaltered in the other time windows. The fact that alterations in SUMO/deSUMOylation equilibrium occur from the early phases of AD suggests that global posttranslational modifications may play an important role in the mechanisms underlying disease pathogenesis, thus providing potential targets for pharmacological interventions.

  6. Dietary DHA supplementation causes selective changes in phospholipids from different brain regions in both wild type mice and the Tg2576 mouse model of Alzheimer's disease.

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    Bascoul-Colombo, Cécile; Guschina, Irina A; Maskrey, Benjamin H; Good, Mark; O'Donnell, Valerie B; Harwood, John L

    2016-06-01

    Alzheimer's disease (AD) is of major concern in ageing populations and we have used the Tg2576 mouse model to understand connections between brain lipids and amyloid pathology. Because dietary docosahexaenoic acid (DHA) has been identified as beneficial, we compared mice fed with a DHA-supplemented diet to those on a nutritionally-sufficient diet. Major phospholipids from cortex, hippocampus and cerebellum were separated and analysed. Each phosphoglyceride had a characteristic fatty acid composition which was similar in cortex and hippocampus but different in the cerebellum. The biggest changes on DHA-supplementation were within ethanolamine phospholipids which, together with phosphatidylserine, had the highest proportions of DHA. Reciprocal alterations in DHA and arachidonate were found. The main diet-induced alterations were found in ethanolamine phospholipids, (and included their ether derivatives), as were the changes observed due to genotype. Tg mice appeared more sensitive to diet with generally lower DHA percentages when on the standard diet and higher relative proportions of DHA when the diet was supplemented. All four major phosphoglycerides analysed showed age-dependent decreases in polyunsaturated fatty acid contents. These data provide, for the first time, a detailed evaluation of phospholipids in different brain areas previously shown to be relevant to behaviour in the Tg2576 mouse model for AD. The lipid changes observed with genotype are consistent with the subtle alterations found in AD patients, especially for the ethanolamine phospholipid molecular species. They also emphasise the contrasting changes in fatty acid content induced by DHA supplementation within individual phospholipid classes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

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    Massaad, Cynthia A.; Amin, Samir K.; Hu, Lingyun; Mei, Yuan

    2010-01-01

    Background Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid β (Aβ) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD. Methodology/Principal Findings In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer. Conclusions/Significance These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology. PMID:20479943

  8. Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease.

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    Cynthia A Massaad

    Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer. CONCLUSIONS/SIGNIFICANCE: These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology.

  9. In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice.

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    Jose Morales-Corraliza

    2009-09-01

    Full Text Available The metabolism of the amyloid precursor protein (APP and tau are central to the pathobiology of Alzheimer's disease (AD. We have examined the in vivo turnover of APP, secreted APP (sAPP, Abeta and tau in the wild-type and Tg2576 mouse brain using cycloheximide to block protein synthesis. In spite of overexpression of APP in the Tg2576 mouse, APP is rapidly degraded, similar to the rapid turnover of the endogenous protein in the wild-type mouse. sAPP is cleared from the brain more slowly, particularly in the Tg2576 model where the half-life of both the endogenous murine and transgene-derived human sAPP is nearly doubled compared to wild-type mice. The important Abeta degrading enzymes neprilysin and IDE were found to be highly stable in the brain, and soluble Abeta40 and Abeta42 levels in both wild-type and Tg2576 mice rapidly declined following the depletion of APP. The cytoskeletal-associated protein tau was found to be highly stable in both wild-type and Tg2576 mice. Our findings unexpectedly show that of these various AD-relevant protein metabolites, sAPP turnover in the brain is the most different when comparing a wild-type mouse and a beta-amyloid depositing, APP overexpressing transgenic model. Given the neurotrophic roles attributed to sAPP, the enhanced stability of sAPP in the beta-amyloid depositing Tg2576 mice may represent a neuroprotective response.

  10. Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration

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    Laursen, Bettina; Mørk, Arne; Plath, Niels

    2013-01-01

    (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory...

  11. Peripheral treatment with enoxaparin exacerbates amyloid plaque pathology in Tg2576 mice.

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    Cui, Hao; King, Anna E; Jacobson, Glenn A; Small, David H

    2017-04-01

    Alzheimer's disease (AD) is a complex, progressive neurological disorder characterized by the formation of extracellular amyloid plaques composed of β-amyloid protein (Aβ), the key component in pathogenesis of AD. Peripheral administration of enoxaparin (ENO) reportedly reduces the level of Aβ and the amyloid plaques in the cortex of amyloid precursor protein (APP) transgenic mice. However, the exact mechanism of these effects is unclear. Our previous studies indicated that ENO can inhibit APP processing to Aβ in primary cortical cells from Tg2576 mice by downregulating BACE1 levels. This study examines whether ENO-induced reduction of amyloid load is due to the decreased APP processing to Aβ in Tg2576 mice. Surprisingly, our results indicated that ENO significantly increases the Aβ42/Aβ40 ratio in cortex and enhances the amyloid plaque load in both cortex and hippocampus, although overall APP processing was not influenced by ENO. Moreover, ENO stimulated the aggregation of both Aβ40 and Aβ42 in vitro. Although ENO has been reported to improve cognition in vivo and has potential as a therapeutic agent for AD, the results from our study suggest that ENO can exacerbate the amyloid pathology, and the strategy of using ENO for the treatment of AD may require further assessment. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. X11beta rescues memory and long-term potentiation deficits in Alzheimer's disease APPswe Tg2576 mice.

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    Mitchell, Jacqueline C

    2009-12-01

    Increased production and deposition of amyloid beta-protein (Abeta) are believed to be key pathogenic events in Alzheimer\\'s disease. As such, routes for lowering cerebral Abeta levels represent potential therapeutic targets for Alzheimer\\'s disease. X11beta is a neuronal adaptor protein that binds to the intracellular domain of the amyloid precursor protein (APP). Overexpression of X11beta inhibits Abeta production in a number of experimental systems. However, whether these changes to APP processing and Abeta production induced by X11beta overexpression also induce beneficial effects to memory and synaptic plasticity are not known. We report here that X11beta-mediated reduction in cerebral Abeta is associated with normalization of both cognition and in vivo long-term potentiation in aged APPswe Tg2576 transgenic mice that model the amyloid pathology of Alzheimer\\'s disease. Overexpression of X11beta itself has no detectable adverse effects upon mouse behaviour. These findings support the notion that modulation of X11beta function represents a therapeutic target for Abeta-mediated neuronal dysfunction in Alzheimer\\'s disease.

  13. Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury.

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    Conte, Valeria; Uryu, Kunihiro; Fujimoto, Scott; Yao, Yuemang; Rokach, Joshua; Longhi, Luca; Trojanowski, John Q; Lee, Virginia M-Y; McIntosh, Tracy K; Praticò, Domenico

    2004-08-01

    Traumatic brain injury is a well-recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven-month-old mice were randomized to receive either regular chow or chow-supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post-injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E-treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Abeta peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Alphabeta accumulation and behavioral impairments in the Tg2576 mice.

  14. Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw mice

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    Karapetyan Adrine

    2008-09-01

    Full Text Available Abstract Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-Aβ28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP transgenic mice (Tg2576. Methods Mannan was purified, activated and chemically conjugated to Aβ28 peptide. Humoral immune responses induced by the immunization of mice with mannan-Aβ28 conjugate were analyzed using a standard ELISA. Aβ42 and Aβ40 amyloid burden, cerebral amyloid angiopathy (CAA, astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-Aβ28 induced potent and long-lasting anti-Aβ humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-Aβ antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-Aβ28 prevented Aβ plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant

  15. Metallothionein family: the multipurpose protein. Influence of Mt1 in the Tg2576 mouse model of ALzheimer's disease

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    Comes Orpinell, Gemma

    2017-01-01

    La malaltia d’Alzheimer és la demència més comuna que afecta el 40% de la població de més de 80 anys d’edat. Amb l’envelliment de la població i la falta de teràpies efectives, s’ha estimat que la prevalença de la malaltia d’aquí 30 anys serà el doble, convertint-se així en una important càrrega sanitària i econòmica. Clínicament, la malaltia d’Alzheimer es defineix per una pèrdua progressiva de funcions cognitives que condueixen a la demència i la mort. Neuropatològicament, destaquen sign...

  16. Age-related synaptic dysfunction in Tg2576 mice starts as a failure in early long-term potentiation which develops into a full abolishment of late long-term potentiation.

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    Fernández-Fernández, Diego; Dorner-Ciossek, Cornelia; Kroker, Katja S; Rosenbrock, Holger

    2016-03-01

    Tg2576 mice are widely used to study amyloid-dependent synaptic dysfunction related to Alzheimer's disease. However, conflicting data have been reported for these mice with regard to basal transmission as well as the in vitro correlate of memory, long-term potentiation (LTP). Some studies show clear impairments, whereas others report no deficiency. The present study uses hippocampal slices from 3-, 10-, and 15-month-old wild-type (WT) and Tg2576 mice to evaluate synaptic function in each group, including experiments to investigate basal synaptic transmission, short- and long-term plasticity by inducing paired-pulse facilitation, and both early and late LTP. We show that synaptic function remains intact in hippocampal slices from Tg2576 mice at 3 months of age. However, both early and late LTP decline progressively during aging in these mice. This deterioration of synaptic plasticity starts affecting early LTP, ultimately leading to the abolishment of both forms of LTP in 15-month-old animals. In comparison, WT littermates display normal synaptic parameters during aging. Additional pharmacological investigation into the involvement of NMDA receptors and L-type voltage-gated calcium channels in LTP suggests a distinct mechanism of induction among age groups, demonstrating that both early and late LTP are differentially affected by these channels in Tg2576 mice during aging. © 2015 Wiley Periodicals, Inc.

  17. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

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    Cribbs David H

    2008-04-01

    Full Text Available Abstract Background Inflammation is associated with Aβ pathology in Alzheimer's disease (AD and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1β and TNF-α which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces Aβ pathology and is neuroprotective. Low concentrations of IFN-γ modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17–19 months Tg2576 mice to a response that reduces Aβ pathology. Methods TG (n = 29 and WT (n = 27 mice were divided into sedentary (SED and exercised (RUN groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 × 2 ANOVA and student's t-tests. Results IL-1β and TNF-α were significantly greater in hippocampi from sedentary Tg2576 (TGSED mice than in wildtype (WTSED (p = 0.04, p = 0.006. Immune response proteins IFN-γ and MIP-1α are lower in TGSED mice than in WTSED (p = 0.03, p = 0.07. Following three weeks of voluntary wheel running, IL-1β and TNF-α decreased to levels indistinguishable from WT. Concurrently, IFN-γ and MIP-1α increased in TGRUN. Increased CD40 and MHCII, markers of antigen presentation, were observed in TGRUN animals compared to TGSED, as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TGRUN is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble Aβ40 (p = 0.01 and soluble fibrillar Aβ (p = 0.01 were observed in the exercised transgenic animals. Conclusion Exercise shifts the immune response from innate to an adaptive or

  18. Culture of Mouse Olfactory Sensory Neurons

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    Gong, Qizhi

    2012-01-01

    Olfactory sensory neurons, located in the nasal epithelium, detect and transmit odorant information to the central nervous system. This requires that these neurons form specific neuronal connections within the olfactory bulb and express receptors and signaling molecules specific for these functions. This protocol describes a primary olfactory sensory neuron culture technique that allows in vitro investigation of olfactory sensory neuron differentiation, axon outgrowth, odorant receptor expres...

  19. Odorant receptor proteins in the mouse main olfactory epithelium and olfactory bulb.

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    Low, Victoria F; Mombaerts, Peter

    2017-03-06

    In the mouse, odorant receptor proteins (ORs) are G-protein-coupled receptors expressed in mature olfactory sensory neurons (OSNs) of the main olfactory epithelium (MOE). ORs mediate odorant reception at the level of the OSN cilia. Most of the ∼1100 OR genes in the mouse genome are expressed, at the RNA level, in mature OSNs. The literature on antibodies against ORs is limited, and most reports are with antibodies that are not commercially available. Here we have screened 40 commercial antibodies against human and mouse ORs by immunofluorescence staining of coronal cryosections of the MOE of 21-day-old C57BL/6J mice. Various methods of antigen retrieval were tested. Of the 19 antibodies raised against human ORs, three yielded a consistent immunoreactive signal in the mouse MOE; of these three, two appeared to cross react against one or more, unknown, mouse ORs. Of the 21 antibodies raised against mouse ORs, six yielded a consistent immunoreactive signal in the mouse MOE; of these six, two also stained specific glomeruli in the olfactory bulb. Antibody specificity could be validated with gene-targeted mouse strains in the case of three ORs. The number of OSNs immunoreactive for the MOR28/Olfr1507 antibody is greater in C57BL/6J than in 129S6/SvEvTac wild-type mice. Taken together, our results are encouraging: 20-30% of these commercially available antibodies are informative in immunohistochemical analyses of the mouse MOE. The commercial availability of these antibodies should facilitate the study of OR proteins in the MOE and the olfactory bulb, and the replicability of results in the literature. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. Olfactory receptors in the mouse septal organ.

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    Kaluza, Jan F; Gussing, Fredrik; Bohm, Staffan; Breer, Heinz; Strotmann, Jörg

    2004-05-15

    In this study we have identified a repertoire of chemosensory receptors expressed in the septal organ (SO). The results suggest that septal organ neurons are specified to express receptor genes belonging to class II olfactory receptors that are also expressed in the main olfactory epithelium. We found no evidence for the expression of members from the vomeronasal receptor gene families. In the SO, no topography analogous to the receptor expression zones of the main olfactory epithelium was evident. The majority of identified receptors corresponds to genes with restricted expression in the medial and lateral zones of the main olfactory epithelium. This coincides with the expression of olfactory cell adhesion molecule (OCAM) throughout the SO, which is considered as a marker for the medial-lateral zones. In contrast, NADPH:quinone oxidoreductase 1 expression, a characteristic marker for the dorsal zone, was lacking in the SO. Most of the receptor types were found to be expressed in rather few SO neurons; as an exception, the receptor mOR244-3 was observed in a very high proportion of cells. Although a very high fraction of SO neurons expressed mOR244-3, we found no evidence for the coexpression of different receptors in individual cells. Copyright 2004 Wiley-Liss, Inc.

  1. Improvements in a Mouse Model of Alzheimer's Disease through Sod2 Overexpression Are Due to Functional and Not Structural Alterations

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    Brittany R. Bitner

    2012-01-01

    Full Text Available Oxidative stress and mitochondrial dysfunction have been implicated in the pathogenesis of Alzheimer's disease. We and others have shown that over expression of the mitochondrial antioxidant superoxide dismutase 2 (SOD-2 can improve many of the pathologies in the Tg2576 mouse model of Alzheimer's disease that harbors the Swedish mutation in the amyloid precursor protein. However, it is not clear if these improvements are due to functional improvements or structural/anatomical changes. To answer this question, we used diffusion tensor imaging (DTI to assess the structural integrity of white matter tracts in the control mice, Tg2576 mouse and Tg2576 mice over expressing SOD-2. We observed minimal differences in diffusion parameters with SOD-2 over expression in this model indicating that the improvements we previously reported are due to functional changes and not any alterations to the white matter tractography.

  2. Severe In Vivo Hyper-Homocysteinemia is not Associated with Elevation of Amyloid-β Peptides in the Tg2576 Mice

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    Zhuo, Jia-Min; Praticò, Domenico

    2010-01-01

    Since hyper-homocysteinemia (HHcy) was recognized as a risk factor for Alzheimer’s disease (AD), many studies tried to induce HHcy in animal models to investigate its effect on amyloid-β protein precursor (AβPP) metabolism. Previous reports found that HHcy induced in AD transgenic mouse models, by either feeding a methionine-enriched diet or vitamin Bs deficient diet, is associated with elevation of amyloid-β (Aβ) levels. However, there is no data available on the effect of dietary interventi...

  3. Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.

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    Géraldine H Petit

    Full Text Available Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.

  4. Ablation of mouse adult neurogenesis alters olfactory bulb structure and olfactory fear conditioning

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    Matthew Valley

    2009-11-01

    Full Text Available Adult neurogenesis replenishes olfactory bulb (OB interneurons throughout the life of most mammals, yet during this constant fl ux it remains unclear how the OB maintains a constant structure and function. In the mouse OB, we investigated the dynamics of turnover and its impact on olfactory function by ablating adult neurogenesis with an x-ray lesion to the subventricular zone (SVZ. Regardless of the magnitude of the lesion to the SVZ, we found no change in the survival of young adult born granule cells (GCs born after the lesion, and a gradual decrease in the population of GCs born before the lesion. After a lesion producing a 96% reduction of incoming adult born GCs to the OB, we found a diminished behavioral fear response to conditioned odor cues but not to audio cues. Interestingly, despite this behavioral defi cit and gradual anatomical changes, we found no electrophysiological changes in the GC population assayed in vivo through dendro-dendritic synaptic plasticity and odor-evoked local fi eld potential oscillations. These data indicate that turnover in the granule cell layer is generally decoupled from the rate of adult neurogenesis, and that OB adult neurogenesis plays a role in a wide behavioral system extending beyond the OB.

  5. A subtype-specific critical period for neurogenesis in the postnatal development of mouse olfactory glomeruli.

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    Yasuko Kato

    Full Text Available Sensory input is essential for the normal development of sensory centers in the brain, such as the somatosensory, visual, auditory, and olfactory systems. Visual deprivation during a specific developmental stage, called the critical period, results in severe and irreversible functional impairments in the primary visual cortex. Olfactory deprivation in the early postnatal period also causes significant developmental defects in the olfactory bulb, the primary center for olfaction. Olfactory bulb interneurons are continuously generated from neural stem cells in the ventricular-subventricular zone, suggesting that the olfactory system has plasticity even in adulthood. Here, we investigated the effect of transient neonatal olfactory deprivation on the addition of interneurons to the glomerular layer of the adult mouse olfactory bulb. We found that the addition of one subtype of interneurons was persistently inhibited even after reopening the naris. BrdU pulse-chase experiments revealed that the neonatal olfactory deprivation predominantly affected an early phase in the maturation of this neuronal subtype in the olfactory bulb. Subjecting the mice to odor stimulation for 6 weeks after naris reopening resulted in significant recovery from the histological and functional defects caused by the olfactory deprivation. These results suggest that a subtype-specific critical period exists for olfactory bulb neurogenesis, but that this period is less strict and more plastic compared with the critical periods for other systems. This study provides new insights into the mechanisms of postnatal neurogenesis and a biological basis for the therapeutic effect of olfactory training.

  6. Functional transformations of odor inputs in the mouse olfactory bulb.

    Science.gov (United States)

    Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

    2014-01-01

    Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams.

  7. Functional transformations of odor inputs in the mouse olfactory bulb

    Science.gov (United States)

    Adam, Yoav; Livneh, Yoav; Miyamichi, Kazunari; Groysman, Maya; Luo, Liqun; Mizrahi, Adi

    2014-01-01

    Sensory inputs from the nasal epithelium to the olfactory bulb (OB) are organized as a discrete map in the glomerular layer (GL). This map is then modulated by distinct types of local neurons and transmitted to higher brain areas via mitral and tufted cells. Little is known about the functional organization of the circuits downstream of glomeruli. We used in vivo two-photon calcium imaging for large scale functional mapping of distinct neuronal populations in the mouse OB, at single cell resolution. Specifically, we imaged odor responses of mitral cells (MCs), tufted cells (TCs) and glomerular interneurons (GL-INs). Mitral cells population activity was heterogeneous and only mildly correlated with the olfactory receptor neuron (ORN) inputs, supporting the view that discrete input maps undergo significant transformations at the output level of the OB. In contrast, population activity profiles of TCs were dense, and highly correlated with the odor inputs in both space and time. Glomerular interneurons were also highly correlated with the ORN inputs, but showed higher activation thresholds suggesting that these neurons are driven by strongly activated glomeruli. Temporally, upon persistent odor exposure, TCs quickly adapted. In contrast, both MCs and GL-INs showed diverse temporal response patterns, suggesting that GL-INs could contribute to the transformations MCs undergo at slow time scales. Our data suggest that sensory odor maps are transformed by TCs and MCs in different ways forming two distinct and parallel information streams. PMID:25408637

  8. Localization of α1-2 Fucose Glycan in the Mouse Olfactory Pathway.

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    Kondoh, Daisuke; Kamikawa, Akihiro; Sasaki, Motoki; Kitamura, Nobuo

    2017-01-01

    Glycoconjugates in the olfactory system play critical roles in neuronal formation, and α1-2 fucose (α1-2Fuc) glycan mediates neurite outgrowth and synaptic plasticity. Histochemical findings of α1-2Fuc glycan in the mouse olfactory system detected using Ulex europaeus agglutinin-I (UEA-I) vary. This study histochemically assessed the main olfactory and vomeronasal pathways in male and female ICR and C57BL/6J mice aged 3-4 months using UEA-I. Ulex europaeus agglutinin-I reacted with most receptor cells arranged mainly at the basal region of the olfactory epithelium. The olfactory nerve layer and glomerular layer of the main olfactory bulb were speckled with positive UEA-I staining, and positive fibers were scattered from the glomerular to the internal plexiform layer. The lateral olfactory tract and rostral migratory stream were also positive for UEA-I. We identified superficial short-axon cells, interneurons of the external plexiform layer, external, middle and internal tufted cells, mitral cells and granule cells as the origins of the UEA-I-positive fibers in the main olfactory bulb. The anterior olfactory nucleus, anterior piriform cortex and olfactory tubercle were negative for UEA-I. Most receptor cells in the vomeronasal epithelium and most glomeruli of the accessory olfactory bulb were positive for UEA-I. Our findings indicated that α1-2Fuc glycan is located within the primary and secondary, but not the ternary, pathways of the main olfactory system, in local circuits of the main olfactory bulb and within the primary, but not secondary, pathway of the vomeronasal system. © 2016 S. Karger AG, Basel.

  9. Functional alterations in the olfactory bulb of the staggerer mutant mouse.

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    Michel, V; Monnier, Z; Guastavino, J M; Propper, A; Math, F

    2000-02-11

    Putative alterations of the functional activity in the staggerer mutant mouse olfactory bulb neuronal network have been studied by recording odor induced evoked field potentials (EFP) in the mitral cells layer. In standard conditions, the main feature observed in mutants was a significant increase in latency preceding the functional response of the mitral cells to the odorant. In these animals, all parameters of the average EFP were widely modified when compared with those recorded in wild mice. Amplitudes and most of the duration of the EFP phases were significantly decreased. Functional alterations were discussed according to the structural disorganization previously described in staggerer mutant mouse olfactory bulb.

  10. An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction

    Science.gov (United States)

    Hutch, Chelsea; Hillard, Cecilia J.; Jia, Cuihong; Hegg, Colleen C.

    2015-01-01

    Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium has not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1 and CB2 receptor deficient (CB1−/−/CB2−/−) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1−/−/CB2−/− mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1−/−/CB2−/− mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted. PMID:26037800

  11. Comprehensive connectivity of the mouse main olfactory bulb: analysis and online digital atlas

    Directory of Open Access Journals (Sweden)

    Houri eHintiryan

    2012-08-01

    Full Text Available We introduce the first open resource for mouse olfactory connectivity data produced as part of the Mouse Connectome Project (MCP at UCLA. The MCP aims to assemble a whole-brain connectivity atlas for the C57Bl/6J mouse using a double coinjection tracing method. Each coinjection consists of one anterograde and one retrograde tracer, which affords the advantage of simultaneously identifying efferent and afferent pathways and directly identifying reciprocal connectivity of injection sites. The systematic application of double coinjections potentially reveals interaction stations between injections and allows for the study of connectivity at the network level. To facilitate use of the data, raw images are made publicly accessible through our online interactive visualization tool, the iConnectome, where users can view and annotate the high-resolution, multi-fluorescent connectivity data (www.MouseConnectome.org. Systematic double coinjections were made into different regions of the main olfactory bulb (MOB and data from 18 MOB cases (~72 pathways; 36 efferent/36 afferent currently are available to view in iConnectome within their corresponding atlas level and their own bright-field cytoarchitectural background. Additional MOB injections and injections of the accessory olfactory bulb (AOB, anterior olfactory nucleus (AON, and other cortical olfactory areas gradually will be made available. Analysis of connections from different regions of the MOB revealed a novel, topographically arranged MOB projection roadmap, demonstrated disparate MOB connectivity with anterior versus posterior piriform cortical area, and exposed some novel aspects of well-established cortical olfactory projections.

  12. Dog and mouse: Towards a balanced view of the mammalian olfactory system

    Directory of Open Access Journals (Sweden)

    William Arthur Barrios Santos

    2014-09-01

    Full Text Available Although the most intensively studied mammalian olfactory system is that of the mouse, in which olfactory chemical cues of one kind or another are detected in four different nasal areas (the main olfactory epithelium, the septal organ, Grüneberg’s ganglion, and the sensory epithelium of the vomeronasal organ, the extraordinarily sensitive olfactory system of the dog is also an important model that is increasingly used, for example in genomic studies of species evolution. Here we describe the topography and extent of the main olfactory and vomeronasal sensory epithelia of the dog, and we report finding no structures equivalent to the Grüneberg ganglion and septal organ of the mouse. Since we examined adults, newborns and foetuses we conclude that these latter structures are absent in dogs, possibly as the result of regression or involution.The absence of a vomeronasal component based on VR2 receptors suggests that the vomeronasal organ may be undergoing a similar involutionary process.

  13. History-Dependent Odor Processing in the Mouse Olfactory Bulb.

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    Vinograd, Amit; Livneh, Yoav; Mizrahi, Adi

    2017-12-06

    In nature, animals normally perceive sensory information on top of backgrounds. Thus, the neural substrate to perceive under background conditions is inherent in all sensory systems. Where and how sensory systems process backgrounds is not fully understood. In olfaction, just a few studies have addressed the issue of odor coding on top of continuous odorous backgrounds. Here, we tested how background odors are encoded by mitral cells (MCs) in the olfactory bulb (OB) of male mice. Using in vivo two-photon calcium imaging, we studied how MCs responded to odors in isolation versus their responses to the same odors on top of continuous backgrounds. We show that MCs adapt to continuous odor presentation and that mixture responses are different when preceded by background. In a subset of odor combinations, this history-dependent processing was useful in helping to identify target odors over background. Other odorous backgrounds were highly dominant such that target odors were completely masked by their presence. Our data are consistent in both low and high odor concentrations and in anesthetized and awake mice. Thus, odor processing in the OB is strongly influenced by the recent history of activity, which could have a powerful impact on how odors are perceived. SIGNIFICANCE STATEMENT We examined a basic feature of sensory processing in the olfactory bulb. Specifically, we measured how mitral cells adapt to continuous background odors and how target odors are encoded on top of such background. Our results show clear differences in odor coding based on the immediate history of the stimulus. Our results support the argument that odor coding in the olfactory bulb depends on the recent history of the sensory environment. Copyright © 2017 Vinograd et al.

  14. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models

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    Gong, Bing; Pan, Yong; Vempati, Prashant; Zhao, Wei; Knable, Lindsay; Ho, Lap; Wang, Jun; Sastre, Magdalena; Ono, Kenjiro; Sauve, Anthony A.; Pasinetti, Giulio M.

    2013-01-01

    Nicotinamide adenine dinucleotide (NAD)+, a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of NAD+ expression has been linked with a decrease in beta-amyloid (Aβ) toxicity in Alzheimer’s disease (AD). Nicotinamide riboside (NR) is a NAD+ precursor, it promotes peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α expression in the brain. Evidence has shown that PGC-1α is a crucial regulator of Aβ generation because it affects β-secretase (BACE1) degradation. In this study we tested the hypothesis that NR treatment in an AD mouse model could attenuate Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation. Using the Tg2576 AD mouse model, using in vivo behavioral analyses, biochemistry assays, small hairpin RNA (shRNA) gene silencing and electrophysiological recording, we found (1) dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD+ in the cerebral cortex; (2) application of NR to hippocampal slices (10 µM) for 4 hours abolishes the deficits in long-term potentiation recorded in the CA1 region of Tg2576 mice; (3) NR treatment promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed that BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos, in which BACE1 degradation was prevented by PGC-1α-shRNA gene silencing; and (4) NR treatment and PGC-1α overexpression enhance BACE1 ubiquitination and proteasomal degradation. Our studies suggest that dietary treatment with NR might benefit AD cognitive function and synaptic plasticity, inpart by promoting PGC-1α-mediated BACE1

  15. Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer's mouse models.

    Science.gov (United States)

    Gong, Bing; Pan, Yong; Vempati, Prashant; Zhao, Wei; Knable, Lindsay; Ho, Lap; Wang, Jun; Sastre, Magdalena; Ono, Kenjiro; Sauve, Anthony A; Pasinetti, Giulio M

    2013-06-01

    Nicotinamide adenine dinucleotide (NAD)(+), a coenzyme involved in redox activities in the mitochondrial electron transport chain, has been identified as a key regulator of the lifespan-extending effects, and the activation of NAD(+) expression has been linked with a decrease in beta-amyloid (Aβ) toxicity in Alzheimer's disease (AD). Nicotinamide riboside (NR) is a NAD(+) precursor, it promotes peroxisome proliferator-activated receptor-γ coactivator 1 (PGC)-1α expression in the brain. Evidence has shown that PGC-1α is a crucial regulator of Aβ generation because it affects β-secretase (BACE1) degradation. In this study we tested the hypothesis that NR treatment in an AD mouse model could attenuate Aβ toxicity through the activation of PGC-1α-mediated BACE1 degradation. Using the Tg2576 AD mouse model, using in vivo behavioral analyses, biochemistry assays, small hairpin RNA (shRNA) gene silencing and electrophysiological recording, we found (1) dietary treatment of Tg2576 mice with 250 mg/kg/day of NR for 3 months significantly attenuates cognitive deterioration in Tg2576 mice and coincides with an increase in the steady-state levels of NAD(+) in the cerebral cortex; (2) application of NR to hippocampal slices (10 μM) for 4 hours abolishes the deficits in long-term potentiation recorded in the CA1 region of Tg2576 mice; (3) NR treatment promotes PGC-1α expression in the brain coinciding with enhanced degradation of BACE1 and the reduction of Aβ production in Tg2576 mice. Further in vitro studies confirmed that BACE1 protein content is decreased by NR treatment in primary neuronal cultures derived from Tg2576 embryos, in which BACE1 degradation was prevented by PGC-1α-shRNA gene silencing; and (4) NR treatment and PGC-1α overexpression enhance BACE1 ubiquitination and proteasomal degradation. Our studies suggest that dietary treatment with NR might benefit AD cognitive function and synaptic plasticity, in part by promoting PGC-1α-mediated BACE1

  16. Drug-induced Parkinson's disease modulates protein kinase A and Olfactory Marker Protein in the mouse olfactory bulb.

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    Mucignat, Carla; Caretta, Antonio

    2017-01-26

    Olfaction is often affected in parkinsonian patients, but dopaminergic cells in the olfactory bulb are not affected by some Parkinson-inducing drugs. We investigated whether the drug MPTP produces the olfactory deficits typical of Parkinson and affects the olfactory bulb in mice. Lesioned and control mice were tested for olfactory search, for motor and exploratory behavior. Brains and olfactory mucosa were investigated via immunohistochemistry for thyrosine hydroxylase, Olfactory Marker Protein and cyclic AMP-dependent protein kinase as an intracellular pathway involved in dopaminergic neurotransmission. MPTP induced motor impairment, but no deficit in olfactory search. Thyrosine hydroxylase did not differ in olfactory bulb, while a strong decrease was detected in substantia nigra and tegmentum of MPTP mice. Olfactory Marker Protein decreased in the olfactory bulb of MPTP mice, while a cyclic AMP-dependent protein kinase increased in the inner granular layer of MPTP mice. MPTP mice do not present behavioural deficits in olfactory search, yet immunoreactivity reveals modifications in the olfactory bulb, and suggests changes in intracellular signal processing, possibly linked to neuron survival after MPTP.

  17. Differential axonal projection of mitral and tufted cells in the mouse main olfactory system.

    Science.gov (United States)

    Nagayama, Shin; Enerva, Allicia; Fletcher, Max L; Masurkar, Arjun V; Igarashi, Kei M; Mori, Kensaku; Chen, Wei R

    2010-01-01

    In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB) glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC) and olfactory tubercle (OT). We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT). Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  18. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Directory of Open Access Journals (Sweden)

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  19. Convergence of FPR-rs3-expressing neurons in the mouse accessory olfactory bulb.

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    Dietschi, Quentin; Assens, Alexis; Challet, Ludivine; Carleton, Alan; Rodriguez, Ivan

    2013-09-01

    In the mouse, most members of the FPR receptor family are expressed by vomeronasal sensory neurons. The neural circuitry corresponding to this class of chemical sensors is unknown. Taking advantage of the presence of FPR-rs3 on both vomeronasal dendrites and axonal fibers, we visualized the distribution of sensory cells expressing this member of the FPR family, and their corresponding axonal projections in the olfactory bulb. We found a rostrocaudal gradient of receptor choice frequency in the vomeronasal sensory neuroepithelium, and observed a convergence of FPR-rs3 axons into multiple, linked and deeply located glomeruli. These were homogenously innervated, and spatially restricted to the basal portion of the rostral accessory olfactory bulb. This organization, reminiscent of the one that characterizes axonal projections of V1R-expressing neurons, supports a role played by these receptors in the perception of semiochemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Olfactory classical conditioning in neonatal mouse pups using thermal stimuli.

    Science.gov (United States)

    Bollen, Bieke; Matrot, Boris; Ramanantsoa, Nelina; Van den Bergh, Omer; D'Hooge, Rudi; Gallego, Jorge

    2012-04-01

    Mouse models are increasingly used to investigate genetic contributions to developmental disorders in children, especially newborns. In particular, early cognitive assessment in newborn mice is critical to evaluate pediatric drug efficacy and toxicity. Unfortunately, methods for behavioral tests in newborn mice are scarce. Therefore, developing such tests for newborn mice is a priority challenge for neurogenetics and pharmacological research. The aim of the present study was to develop a conditioning method well suited to high-throughput cognitive screening in newborn mice. To this end, we developed an odor-preference conditioning test using ambient temperature as an unconditioned stimulus (US) and artificial odors as conditioned stimuli (CS). First, we showed that mouse pups move toward the thermoneutral temperature when offered a choice between a thermoneutral and cold environment, thus showing thermotaxis. Second, we conducted a classical conditioning paradigm in pups aged six to ten days. In terms of central nervous system development, this period corresponds to extreme prematurity to early post-term period in humans. During acquisition, the pups were alternatively exposed to odor CS paired with either cold or warm temperatures. Immediately after acquisition, the pups underwent a two-odor choice test, which showed preference for the odor previously paired with the warm temperature, thus showing conditioning. The proposed paradigm is easy to conduct, and requires modest experimenter interference. The method is well suited for high-throughput screening of early associative disorders in newborn mice. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Gustatory, trigeminal, and olfactory aspects of nicotine intake in three mouse strains.

    Science.gov (United States)

    Gyekis, Joseph P; Dingman, Marc A; Revitsky, Alicia R; Bryant, Bruce P; Vandenbergh, David J; Frank, Marion E; Blizard, David A

    2012-09-01

    Studies of nicotine consumption in rodents often intend to investigate nicotine's post-absorptive effects, yet little is known about the pre-absorptive sensory experience of nicotine drinking, including gustatory, trigeminal, and olfactory influences. We conditioned taste aversion (CTA) to nicotine in males of 3 inbred mouse strains: C57BL/6J, DBA/2J, and 129X1/SvJ by repeatedly pairing 150 μg/ml nicotine drinking with lithium chloride injections. Generalization to a variety of bitter, sour, sweet, salty, and irritant solutions and to nicotine odor was then examined. Nicotine CTA generalized to the bitter stimulus quinine hydrochloride and the chemosensory irritant spilanthol in all strains. It also showed strain specificity, generalizing to hydrogen peroxide (an activator of TRPA1) in C57BL/6J mice and to the olfactory cue of nicotine in DBA/2J mice. These behavioral assays demonstrate that the sensory properties of nicotine are complex and include multiple gustatory, irritant, and olfactory components. How these qualities combine at the level of perception remains to be assessed, but sensory factors clearly exert an important influence on nicotine ingestion and their contribution to net intake of nicotine should not be neglected in animal or human studies.

  2. Increased Olfactory Bulb BDNF Expression Does Not Rescue Deficits in Olfactory Neurogenesis in the Huntington's Disease R6/2 Mouse.

    Science.gov (United States)

    Smail, Shamayra; Bahga, Dalbir; McDole, Brittnee; Guthrie, Kathleen

    2016-03-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin protein (mhtt) interferes with the actions of brain-derived neurotrophic factor (BDNF), and BDNF signaling is reduced in the diseased striatum. Loss of this trophic support is thought to contribute to loss of striatal medium spiny neurons in HD. Increasing BDNF in the adult striatum or ventricular ependyma slows disease progression in HD mouse models, and diverts subventricular zone (SVZ)-derived neuroblasts from their normal destination, the olfactory bulb, to the striatum, where some survive and develop features of mature neurons. Most neuroblasts that migrate to the olfactory bulb differentiate as granule cells, with approximately half surviving whereas others undergo apoptosis. In the R6/2 HD mouse model, survival of adult-born granule cells is reduced. Newly maturing cells express the BDNF receptor TrkB, suggesting that mhtt may interfere with normal BDNF trophic activity, increasing their loss. To determine if augmenting BDNF counteracts this, we examined granule cell survival in R6/2 mice that overexpress BDNF in olfactory bulb. Although we detected a decline in apoptosis, increased BDNF was not sufficient to normalize granule cell survival within their normal target in R6/2 mice. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Serine/threonine-protein phosphatase 1 α levels are paralleling olfactory memory formation in the CD1 mouse.

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    Winding, Christiana; Sun, Yanwei; Höger, Harald; Bubna-Littitz, Hermann; Pollak, Arnold; Schmidt, Peter; Lubec, Gert

    2011-06-01

    Although olfactory discrimination has already been studied in several mouse strains, data on protein levels linked to olfactory memory are limited. Wild mouse strains Mus musculus musculus, Mus musculus domesticus and CD1 laboratory outbred mice were tested in a conditioned odor preference task and trained to discriminate between two odors, Rose and Lemon, by pairing one odor with a sugar reward. Six hours following the final test, mice were sacrificed and olfactory bulbs (OB) were taken for gel-based proteomics analyses and immunoblotting. OB proteins were extracted, separated by 2-DE and quantified using specific software (Proteomweaver). Odor-trained mice showed a preference for the previously rewarded odor suggesting that conditioned odor preference occurred. In CD1 mice levels, one out of 482 protein spots was significantly increased in odor-trained mice as compared with the control group; it was in-gel digested by trypsin and chymotrypsin and analyzed by tandem mass spectrometry (nano-ESI-LC-MS/MS). The spot was unambiguously identified as serine/threonine-protein phosphatase PP1-α catalytic subunit (PP-1A) and differential levels observed in gel-based proteomic studies were verified by immunoblotting. PP-1A is a key signalling element in synaptic plasticity and memory processes and is herein shown to be paralleling olfactory discrimination representing olfactory memory. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mechanisms of constitutive and ATP-evoked ATP release in neonatal mouse olfactory epithelium

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    Hayoz Sébastien

    2012-05-01

    Full Text Available Abstract Background ATP is an extracellular signaling molecule with many ascribed functions in sensory systems, including the olfactory epithelium. The mechanism(s by which ATP is released in the olfactory epithelium has not been investigated. Quantitative luciferin-luciferase assays were used to monitor ATP release, and confocal imaging of the fluorescent ATP marker quinacrine was used to monitor ATP release via exocytosis in Swiss Webster mouse neonatal olfactory epithelial slices. Results Under control conditions, constitutive release of ATP occurs via exocytosis, hemichannels and ABC transporters and is inhibited by vesicular fusion inhibitor Clostridium difficile toxin A and hemichannel and ABC transporter inhibitor probenecid. Constitutive ATP release is negatively regulated by the ATP breakdown product ADP through activation of P2Y receptors, likely via the cAMP/PKA pathway. In vivo studies indicate that constitutive ATP may play a role in neuronal homeostasis as inhibition of exocytosis inhibited normal proliferation in the OE. ATP-evoked ATP release is also present in mouse neonatal OE, triggered by several ionotropic P2X purinergic receptor agonists (ATP, αβMeATP and Bz-ATP and a G protein-coupled P2Y receptor agonist (UTP. Calcium imaging of P2X2-transfected HEK293 “biosensor” cells confirmed the presence of evoked ATP release. Following purinergic receptor stimulation, ATP is released via calcium-dependent exocytosis, activated P2X1,7 receptors, activated P2X7 receptors that form a complex with pannexin channels, or ABC transporters. The ATP-evoked ATP release is inhibited by the purinergic receptor inhibitor PPADS, Clostridium difficile toxin A and two inhibitors of pannexin channels: probenecid and carbenoxolone. Conclusions The constitutive release of ATP might be involved in normal cell turn-over or modulation of odorant sensitivity in physiological conditions. Given the growth-promoting effects of ATP, ATP-evoked ATP

  5. Linear correlation between the number of olfactory sensory neurons expressing a given mouse odorant receptor gene and the total volume of the corresponding glomeruli in the olfactory bulb.

    Science.gov (United States)

    Bressel, Olaf Christian; Khan, Mona; Mombaerts, Peter

    2016-01-01

    Chemosensory specificity in the main olfactory system of the mouse relies on the expression of ∼1,100 odorant receptor (OR) genes across millions of olfactory sensory neurons (OSNs) in the main olfactory epithelium (MOE), and on the coalescence of OSN axons into ∼3,600 glomeruli in the olfactory bulb. A traditional approach for visualizing OSNs and their axons consists of tagging an OR gene genetically with an axonal marker that is cotranslated with the OR by virtue of an internal ribosome entry site (IRES). Here we report full cell counts for 15 gene-targeted strains of the OR-IRES-marker design coexpressing a fluorescent protein. These strains represent 11 targeted OR genes, a 1% sample of the OR gene repertoire. We took an empirical, "count every cell" strategy: we counted all fluorescent cell profiles with a nuclear profile within the cytoplasm, on all serial coronal sections under a confocal microscope, a total of 685,673 cells in 56 mice at postnatal day 21. We then applied a strain-specific Abercrombie correction to these OSN counts in order to obtain a closer approximation of the true OSN numbers. We found a 17-fold range in the average (corrected) OSN number across these 11 OR genes. In the same series of coronal sections, we then determined the total volume of the glomeruli (TGV) formed by coalescence of the fluorescent axons. We found a strong linear correlation between OSN number and TGV, suggesting that TGV can be used as a surrogate measurement for estimating OSN numbers in these gene-targeted strains. © 2015 The Authors. The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  6. Minocycline reduces spontaneous hemorrhage in mouse models of cerebral amyloid angiopathy.

    Science.gov (United States)

    Yan, Ping; Zhu, Alec; Liao, Fan; Xiao, Qingli; Kraft, Andrew; Gonzales, Ernie; Perez, Ron; Greenberg, Steven M; Holtzman, David; Lee, Jin-Moo

    2015-06-01

    Cerebral amyloid angiopathy (CAA) is a common cause of recurrent intracerebral hemorrhage in the elderly. Previous studies have shown that CAA induces inflammation and expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 (gelatinases) in amyloid-laden vessels. Here, we inhibited both using minocycline in CAA mouse models to determine whether spontaneous intracerebral hemorrhage could be reduced. Tg2576 (n=16) and 5xFAD/ApoE4 knockin mice (n=16), aged 17 and 12 months, respectively, were treated with minocycline (50 mg/kg, IP) or saline every other day for 2 months. Brains were extracted and stained with X-34 (to quantify amyloid), Perls' blue (to quantify hemorrhage), and immunostained to examined β-amyloid peptide load, gliosis (glial fibrillary acidic protein [GFAP], Iba-1), and vascular markers of blood-brain barrier integrity (zonula occludins-1 [ZO-1] and collagen IV). Brain extracts were used to quantify mRNA for a variety of inflammatory genes. Minocycline treatment significantly reduced hemorrhage frequency in the brains of Tg2576 and 5xFAD/ApoE4 mice relative to the saline-treated mice, without affecting CAA load. Gliosis (GFAP and Iba-1 immunostaining), gelatinase activity, and expression of a variety of inflammatory genes (matrix metalloproteinase-9, NOX4, CD45, S-100b, and Iba-1) were also significantly reduced. Higher levels of microvascular tight junction and basal lamina proteins were found in the brains of minocycline-treated Tg2576 mice relative to saline-treated controls. Minocycline reduced gliosis, inflammatory gene expression, gelatinase activity, and spontaneous hemorrhage in 2 different mouse models of CAA, supporting the importance of matrix metalloproteinase-related and inflammatory pathways in intracerebral hemorrhage pathogenesis. As a Food and Drug Administration-approved drug, minocycline might be considered for clinical trials to test efficacy in preventing CAA-related intracerebral hemorrhage. © 2015 American

  7. Kinetics of chemically mediated neurodegeneration/neuroregeneration of mouse olfactory epithelium: monitoring by hyperlayer sedimentation field flow fractionation.

    Science.gov (United States)

    Mitais, N; Bessette, B; Gobron, S; Cardot, P; Jauberteau, M O; Battu, S; Lalloué, F

    2014-02-01

    The increase in the incidence of neurodegenerative diseases linked to aging or injury needs to be addressed in research into neuroprotective or neuroregenerative therapies, and requires the development of specific biological models. To achieve this goal we propose (1) the use of the mouse olfactory epithelium as a biological support which specifically exhibits a regenerative or a self-renewing capacity and during the lifetime necessitates the presence of neural stem cells, and (2) the use of an intraperitoneal injection of 2,6-dichlorobenzonitrile (diclobenil) as a chemical inducer of neurodegeneration in olfactory epithelium by selectively killing mature cells. We developed a biological model to follow the processes of neurodegeneration (chemically induced) and neuroregeneration (self-renewal of olfactory epithelium). The purpose of this study was to develop a method to monitor quickly neurodegeneration/neuroregeneration processes in order to further screen protective and regenerative therapies. For this purpose, we used the sedimentation field flow fractionation elution of olfactory epithelium. We obtained specific elution profiles and retention parameters allowing the monitoring of the induction and kinetics of biological processes. The use of insulin-like growth factor 1α as a neuroprotective agent in an innovative nebulization protocol showed sedimentation field flow fractionation to be a simple, fast and low-cost method to monitor such a biological event on the scale of an entire organism.

  8. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium.

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2012-02-01

    BACKGROUND: Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. RESULTS: Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. CONCLUSION: Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  9. Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium

    LENUS (Irish Health Repository)

    Dooley, Ruth

    2011-08-22

    Abstract Background Extracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation. Results Here we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells. Conclusion Our results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.

  10. Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli

    Science.gov (United States)

    Fried, Hans U.; Fuss, Stefan H.; Korsching, Sigrun I.

    2002-03-01

    More chemicals can be smelled than there are olfactory receptors for them, necessitating a combinatorial representation by somewhat broadly tuned receptors. To understand the perception of odor quality and concentration, it is essential to establish the nature of the receptor repertoires that are activated by particular odorants at particular concentrations. We have taken advantage of the one-to-one correspondence of glomeruli and olfactory receptor molecules in the mouse olfactory bulb to analyze the tuning properties of a major receptor population by high resolution calcium imaging of odor responses selectively in the presynaptic compartment of glomeruli. We show that eighty different olfactory receptors projecting to the dorsal olfactory bulb respond to high concentrations of aldehydes with limited specificity. Varying ensembles of about 10 to 20 receptors encode any particular aldehyde at low stimulus concentrations with high specificity. Even normalized odor response patterns are markedly concentration dependent, caused by pronounced differences in affinity within the aldehyde receptor repertoire.

  11. Effects of oral aluminum exposure on behavior and neurogenesis in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Ribes, D; Colomina, M T; Vicens, P; Domingo, J L

    2008-12-01

    The effects of a very low oral dose of Al on spatial learning and neurogenesis were evaluated in a transgenic mouse (Tg 2576) model of Alzheimer disease. At 5 months of age, wild and Tg 2576 mice received a diet supplemented with Al lactate at 0 and 1 mg/g of diet for 120 days. The experimental groups (n=7-8) were: control wild, Al-treated wild, control transgenic, and Al-treated transgenic. After 3 months of Al exposure, activity in an open-field and learning in a water maze were evaluated. At the end of the behavioral testing, in order to study cell proliferation and differentiation in the hippocampus, mice were injected with 5-bromo-2-deoxyuridine (BrdU) and sacrificed 1 or 28 days after the last BrdU injection. Tg 2576 mice were impaired in both acquisition and retention of the water maze task, showing higher amounts of beta-amyloid fragments in brain. Aluminum exposure impaired learning and memory in wild mice and increased the total number of proliferating cells in the dentate gyrus of hippocampus. The low Al doses here experimented suggest that this element might impair cognition in the general population at doses comparable to current levels of human exposure. Although these doses are not enough to interact with the amyloidogenic pathway, an increase in cell proliferation can indicate a reactive response of the brain to Al insult. Further investigations should be performed to corroborate the effects observed at very low doses of Al and to study the potential effects derived from a longer exposure period.

  12. Olfactory Perceptual Learning Requires Action of Noradrenaline in the Olfactory Bulb: Comparison with Olfactory Associative Learning

    Science.gov (United States)

    Vinera, Jennifer; Kermen, Florence; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie; Richard, Marion

    2015-01-01

    Noradrenaline contributes to olfactory-guided behaviors but its role in olfactory learning during adulthood is poorly documented. We investigated its implication in olfactory associative and perceptual learning using local infusion of mixed a1-ß adrenergic receptor antagonist (labetalol) in the adult mouse olfactory bulb. We reported that…

  13. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs

    Directory of Open Access Journals (Sweden)

    Philipp eHohenbrink

    2014-09-01

    Full Text Available The vomeronasal organ (VNO is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR genes comprise two families of chemosensory genes (V1R and V2R that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the grey mouse lemur (Microcebus murinus, the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83% – 97% of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29% to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

  14. Functional promiscuity in a mammalian chemosensory system: extensive expression of vomeronasal receptors in the main olfactory epithelium of mouse lemurs.

    Science.gov (United States)

    Hohenbrink, Philipp; Dempewolf, Silke; Zimmermann, Elke; Mundy, Nicholas I; Radespiel, Ute

    2014-01-01

    The vomeronasal organ (VNO) is functional in most terrestrial mammals, though progressively reduced in the primate lineage, and is used for intraspecific communication and predator recognition. Vomeronasal receptor (VR) genes comprise two families of chemosensory genes (V1R and V2R) that have been considered to be specific for the VNO. However, recently a large number of VRs were reported to be expressed in the main olfactory epithelium (MOE) of mice, but there is little knowledge of the expression of these genes outside of rodents. To explore the function of VR genes in mammalian evolution, we analyzed and compared the expression of 64 V1R and 2 V2R genes in the VNO and the MOE of the gray mouse lemur (Microcebus murinus), the primate with the largest known VR repertoire. We furthermore compared expression patterns in adults of both sexes and seasons, and in an infant. A large proportion (83-97%) of the VR loci was expressed in the VNO of all individuals. The repertoire in the infant was as rich as in adults, indicating reliance on olfactory communication from early postnatal development onwards. In concordance with mice, we also detected extensive expression of VRs in the MOE, with proportions of expressed loci in individuals ranging from 29 to 45%. TRPC2, which encodes a channel protein crucial for signal transduction via VRs, was co-expressed in the MOE in all individuals indicating likely functionality of expressed VR genes in the MOE. In summary, the large VR repertoire in mouse lemurs seems to be highly functional. Given the differences in the neural pathways of MOE and VNO signals, which project to higher cortical brain centers or the limbic system, respectively, this raises the intriguing possibility that the evolution of MOE-expression of VRs enabled mouse lemurs to adaptively diversify the processing of VR-encoded olfactory information.

  15. Two mirror-image sensory maps with domain organization in the mouse main olfactory bulb.

    Science.gov (United States)

    Nagao, H; Yoshihara, Y; Mitsui, S; Fujisawa, H; Mori, K

    2000-09-11

    The glomerular sheet in the olfactory bulb (OB) provides an olfactory sensory map identifying which odorant receptors (ORs) in the nose are activated by inhaled odorants. How are the glomeruli spatially arranged in the OB? Using OCAM and neuropilin-1 (NP1) as molecular markers for target glomeruli of distinct subsets of olfactory axons, we demonstrate here that glomeruli are parceled into topographically distinct domains. Spatial arrangement of these domains suggests that each OB contains two mirror-image maps of the glomeruli. In situ hybridization shows that the glomeruli representing the same OR are symmetrically arranged; one in a domain in the lateral hemisphere and the other in a corresponding domain in the medial hemisphere of the OB. These results suggest that OB contains two symmetrical OR maps with similar domain organization.

  16. DNA polymerase β decrement triggers death of olfactory bulb cells and impairs olfaction in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Misiak, Magdalena; Vergara Greeno, Rebeca; Baptiste, Beverly A; Sykora, Peter; Liu, Dong; Cordonnier, Stephanie; Fang, Evandro F; Croteau, Deborah L; Mattson, Mark P; Bohr, Vilhelm A

    2017-02-01

    Alzheimer's disease (AD) involves the progressive degeneration of neurons critical for learning and memory. In addition, patients with AD typically exhibit impaired olfaction associated with neuronal degeneration in the olfactory bulb (OB). Because DNA base excision repair (BER) is reduced in brain cells during normal aging and AD, we determined whether inefficient BER due to reduced DNA polymerase-β (Polβ) levels renders OB neurons vulnerable to degeneration in the 3xTgAD mouse model of AD. We interrogated OB histopathology and olfactory function in wild-type and 3xTgAD mice with normal or reduced Polβ levels. Compared to wild-type control mice, Polβ heterozygous (Polβ+/- ), and 3xTgAD mice, 3xTgAD/Polβ+/- mice exhibited impaired performance in a buried food test of olfaction. Polβ deficiency did not affect the proliferation of OB neural progenitor cells in the subventricular zone. However, numbers of newly generated neurons were reduced by approximately 25% in Polβ+/- and 3xTgAD mice, and by over 60% in the 3xTgAD/Polβ+/- mice compared to wild-type control mice. Analyses of DNA damage and apoptosis revealed significantly greater degeneration of OB neurons in 3xTgAD/Polβ+/- mice compared to 3xTgAD mice. Levels of amyloid β-peptide (Aβ) accumulation in the OB were similar in 3xTgAD and 3xTgAD/Polβ+/- mice, and cultured Polβ-deficient neurons exhibited increased vulnerability to Aβ-induced death. Olfactory deficit is an early sign in human AD, but the mechanism is not yet understood. Our findings in a new AD mouse model demonstrate that diminution of BER can endanger OB neurons, and suggest a mechanism underlying early olfactory impairment in AD. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  17. The mouse olfactory peduncle. 3. Development of neurons, glia and centrifugal afferents

    Directory of Open Access Journals (Sweden)

    Peter eBrunjes

    2014-06-01

    Full Text Available The present series of studies was designed to provide a general overview of the development of the region connecting the olfactory bulb to the forebrain. The olfactory peduncle contains several structures involved in processing odor information with the anterior olfactory nucleus (cortex being the largest and most studied. Results indicate that considerable growth occurs in the peduncle from postnatal day (P10-P20, with reduced expansion from P20-P30. No evidence was found for the addition of new projection or interneurons during the postnatal period. GABAergic cells decreased in both number and density after P10. Glial populations exhibited different patterns of development, with astrocytes declining in density from P10-P30, and both oligodendrocytes and microglia increasing through the interval. Myelination in the anterior commissure emerged between P11-14. Dense cholinergic innervation was observed at P10 and remained relatively stable through P30, while considerable maturation of serotonergic innervation occurred through the period. Unilateral naris occlusion from P1-P30 resulted in about a 30% reduction in the size of the ipsilateral peduncle but few changes were observed on the contralateral side. The ipsilateral peduncle also exhibited higher densities of GAD67- containing interneurons and cholinergic fibers suggesting a delay in normal developmental pruning. Lower densities of interneurons expressing CCK, somatostatin and NPY and in myelin basic protein staining were also observed. Understanding variations in developmental trajectories within the olfactory peduncle may be an important tool for unravelling the functions of the region.

  18. Anesthetic regimes modulate the temporal dynamics of local field potential in the mouse olfactory bulb.

    Science.gov (United States)

    Chery, Romain; Gurden, Hirac; Martin, Claire

    2014-03-01

    Anesthetized preparations have been widely used to study odor-induced temporal dynamics in the olfactory bulb. Although numerous recent data of single-cell recording or imaging in the olfactory bulb have employed ketamine cocktails, their effects on networks activities are still poorly understood, and odor-induced oscillations of the local field potential have not been characterized under these anesthetics. Our study aimed at describing the impact of two ketamine cocktails on oscillations and comparing them to awake condition. Anesthesia was induced by injection of a cocktail of ketamine, an antagonist of the N-methyl-d-aspartate receptors, combined with one agonist of α2-adrenergic receptors, xylazine (low affinity) or medetomidine (high affinity). Spontaneous and odor-induced activities were examined in anesthetized and awake conditions, in the same mice chronically implanted with an electrode in the main olfactory bulb. The overall dynamic pattern of oscillations under the two ketamine cocktails resembles that of the awake state. Ongoing activity is characterized by gamma bursts (>60 Hz) locked on respiration and beta (15-40 Hz) power increases during odor stimulation. However, anesthesia decreases local field potential power and leads to a strong frequency shift of gamma oscillations from 60-90 Hz to 100-130 Hz. We conclude that similarities between oscillations in anesthetized and awake states make cocktails of ketamine with one α2-agonist suitable for the recordings of local field potential to study processing in the early stages of the olfactory system.

  19. Glomerular input patterns in the mouse olfactory bulb evoked by retronasal odor stimuli.

    Science.gov (United States)

    Furudono, Yuichi; Cruz, Ginny; Lowe, Graeme

    2013-04-08

    Odorant stimuli can access the olfactory epithelium either orthonasally, by inhalation through the external nares, or retronasally by reverse airflow from the oral cavity. There is evidence that odors perceived through these two routes can differ in quality and intensity. We were curious whether such differences might potentially have a neural basis in the peripheral mechanisms of odor coding. To explore this possibility, we compared olfactory receptor input to glomeruli in the dorsal olfactory bulb evoked by orthonasal and retronasal stimulation. Maps of glomerular response were acquired by optical imaging of transgenic mice expressing synaptopHluorin (spH), a fluorescent reporter of presynaptic activity, in olfactory nerve terminals. We found that retronasally delivered odorants were able to activate inputs to multiple glomeruli in the dorsal olfactory bulb. The retronasal responses were smaller than orthonasal responses to odorants delivered at comparable concentrations and flow rates, and they displayed higher thresholds and right-shifted dose-response curves. Glomerular maps of orthonasal and retronasal responses were usually well overlapped, with fewer total numbers of glomeruli in retronasal maps. However, maps at threshold could be quite distinct with little overlap. Retronasal responses were also more narrowly tuned to homologous series of aliphatic odorants of varying carbon chain length, with longer chain, more hydrophobic compounds evoking little or no response at comparable vapor levels. Several features of retronasal olfaction are possibly referable to the observed properties of glomerular odorant responses. The finding that retronasal responses are weaker and sparser than orthonasal responses is consistent with psychophysical studies showing lower sensitivity for retronasal olfaction in threshold and suprathreshold tests. The similarity and overlap of orthonasal and retronasal odor maps at suprathreshold concentrations agrees with generally similar

  20. Novel subdomains of the mouse olfactory bulb defined by molecular heterogeneity in the nascent external plexiform and glomerular layers

    Directory of Open Access Journals (Sweden)

    Yona Golan

    2007-05-01

    Full Text Available Abstract Background In the mouse olfactory system, the role of the olfactory bulb in guiding olfactory sensory neuron (OSN axons to their targets is poorly understood. What cell types within the bulb are necessary for targeting is unknown. What genes are important for this process is also unknown. Although projection neurons are not required, other cell-types within the external plexiform and glomerular layers also form synapses with OSNs. We hypothesized that these cells are important for targeting, and express spatially differentially expressed guidance cues that act to guide OSN axons within the bulb. Results We used laser microdissection and microarray analysis to find genes that are differentially expressed along the dorsal-ventral, medial-lateral, and anterior-posterior axes of the bulb. The expression patterns of these genes divide the bulb into previously unrecognized subdomains. Interestingly, some genes are expressed in both the medial and lateral bulb, showing for the first time the existence of symmetric expression along this axis. We use a regeneration paradigm to show that several of these genes are altered in expression in response to deafferentation, consistent with the interpretation that they are expressed in cells that interact with OSNs. Conclusion We demonstrate that the nascent external plexiform and glomerular layers of the bulb can be divided into multiple domains based on the expression of these genes, several of which are known to function in axon guidance, synaptogenesis, and angiogenesis. These genes represent candidate guidance cues that may act to guide OSN axons within the bulb during targeting.

  1. Chronic exposure to aluminum and melatonin through the diet: neurobehavioral effects in a transgenic mouse model of Alzheimer disease.

    Science.gov (United States)

    Di Paolo, Celeste; Reverte, Ingrid; Colomina, Maria Teresa; Domingo, José L; Gómez, Mercedes

    2014-07-01

    Aluminum (Al) is a known neurotoxic element involved in the etiology of some serious neurodegenerative disorders such as Alzheimer disease (AD). Antioxidants like melatonin might protect neurons against the damage produced in AD. The APPSWE (Tg2576) transgenic mouse is one of the most used animal models developed to mimic AD damage. In the present study, wild type and Tg2576 mice were orally exposed during 14 months to Al, melatonin, and citric acid, as well as to all possible combinations between them. At 17 months of age, mice were evaluated for behavior using the open-field test and the Morris water maze. Transgenic animals exposed to melatonin only and to Al plus citric acid plus melatonin showed a good acquisition. No effects on acquisition in the Morris water maze were observed in wild type mice. With respect to the retention of the task, only melatonin wild type animals, and Al plus citric acid plus melatonin transgenic mice showed retention during the acquisition. Control wild type animals and Al plus citric acid plus melatonin transgenic mice showed good long term retention. Melatonin improved learning and spatial memory in Al-exposed transgenic mice. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Musthafa Mohamed Essa

    Full Text Available Alzheimer's disease (AD is a devastating age-related neurodegenerative disease with no specific treatment at present. The APPsw/Tg2576 mice exhibit age-related deterioration in memory and learning as well as amyloid-beta (Aβ accumulation, and this mouse strain is considered an effective model for studying the mechanism of accelerated brain aging and senescence. The present study was aimed to investigate the beneficial effects of dietary supplements pomegranate, figs, or the dates on suppressing inflammatory cytokines in APPsw/Tg2576 mice. Changes in the plasma cytokines and Aβ, ATP, and inflammatory cytokines were investigated in the brain of transgenic mice. Significantly enhanced levels of inflammatory cytokines IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, TNF-α and Eotaxin activity were decreased by administration of the diet supplements containing pomegranates, figs, or dates. In addition, putative delays in the formation of senile plaques, as indicated by a decreasing tendency of brain Aβ1-40 and Aβ1-42 contents, were observed. Thus, novel results mediated by reducing inflammatory cytokines during aging may represent one mechanism by which these supplements exert their beneficial effects against neurodegenerative diseases such as AD.

  3. Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Zhong-Hao Zhang

    2016-09-01

    Full Text Available Olfactory dysfunction is an early and common symptom in Alzheimer′s disease (AD and is reported to be related to several pathologic changes, including the deposition of Aβ and hyperphosphorylated tau protein as well as synaptic impairment. Selenomethionine (Se-Met, the major form of selenium in animals and humans, may be a promising therapeutic option for AD as it decreases the deposition of Aβ and tau hyperphosphorylation in a triple transgenic mouse model of AD (3× Tg-AD. In this study, 4-month-old AD mice were treated with 6 µg/mL Se-Met in drinking water for 12 weeks and the effect of Se-Met on neuropathological deficits in olfactory bulb (OB of 3× Tg-AD mice was investigated. The administration of Se-Met effectively decreased the production and deposition of Aβ by inhibiting β-site amyloid precursor protein cleaving enzyme 1 (BACE1-regulated amyloid precursor protein (APP processing and reduced the level of total tau and phosphorylated tau, which depended on depressing the activity and expression of glycogen synthase kinase-3β (GSK-3β and cyclin-dependent kinase 5 (CDK5. Meanwhile, Se-Met reduced glial activation, relieved neuroinflammation and attenuated neuronal cell death in the OB of AD mice. So Se-Met could improve pathologic changes of AD in the OB, which further demonstrated the potential therapeutic effect of Se-Met in AD.

  4. Differential expression of components of the retinoic acid signaling pathway in the adult mouse olfactory epithelium.

    Science.gov (United States)

    Peluso, Carolyn E; Jang, Woochan; Dräger, Ursula C; Schwob, James E

    2012-11-01

    Position within a tissue often correlates with cellular phenotype, for example, differential expression of odorant receptors and cell adhesion molecules across the olfactory mucosa (OM). The association between position and phenotype is often paralleled by gradations in the concentration of retinoic acid (RA), caused by differential expression of the RA synthetic enzymes, the retinaldehyde dehydrogenases (RALDH). We show here that RALDH-1, -2, and -3 are enriched in the sustentacular cells, deep fibroblasts of the lamina propria, and the superficial fibroblasts, respectively, of the ventral and lateral OM as compared to the dorsomedial OM. The shift from high to low expression of the RALDHs matches the boundary defined by the differential expression of OCAM/mamFasII. Further, we found that RA-binding proteins are expressed in the epithelium overlying the RALDH-3 expressing fibroblasts of the lamina propria. Both findings suggest that local alterations in RA concentration may be more important than a gradient of RA across the epithelial plane, per se. In addition, RALDH-3 is found in a small population of basal cells in the ventral and lateral epithelium, which expand and contribute to the neuronal lineage following MeBr lesion. Indeed, transduction with a retrovirus expressing a dominant negative form of retinoic acid receptor type alpha blocks the reappearance of mature, olfactory marker protein (OMP) (+) olfactory neurons as compared to empty vector. These results support the notion of a potential role for RA, both in maintaining the spatial organization of the normal olfactory epithelium and in reestablishing the neuronal population during regeneration after injury. Copyright © 2012 Wiley Periodicals, Inc.

  5. Structural basis for cholinergic regulation of neural circuits in the mouse olfactory bulb.

    Science.gov (United States)

    Hamamoto, Masakazu; Kiyokage, Emi; Sohn, Jaerin; Hioki, Hiroyuki; Harada, Tamotsu; Toida, Kazunori

    2017-02-15

    Odor information is regulated by olfactory inputs, bulbar interneurons, and centrifugal inputs in the olfactory bulb (OB). Cholinergic neurons projecting from the nucleus of the horizontal limb of the diagonal band of Broca and the magnocellular preoptic nucleus are one of the primary centrifugal inputs to the OB. In this study, we focused on cholinergic regulation of the OB and analyzed neural morphology with a particular emphasis on the projection pathways of cholinergic neurons. Single-cell imaging of a specific neuron within dense fibers is critical to evaluate the structure and function of the neural circuits. We labeled cholinergic neurons by infection with virus vector and then reconstructed them three-dimensionally. We also examined the ultramicrostructure of synapses by electron microscopy tomography. To further clarify the function of cholinergic neurons, we performed confocal laser scanning microscopy to investigate whether other neurotransmitters are present within cholinergic axons in the OB. Our results showed the first visualization of complete cholinergic neurons, including axons projecting to the OB, and also revealed frequent axonal branching within the OB where it innervated multiple glomeruli in different areas. Furthermore, electron tomography demonstrated that cholinergic axons formed asymmetrical synapses with a morphological variety of thicknesses of the postsynaptic density. Although we have not yet detected the presence of other neurotransmitters, the range of synaptic morphology suggests multiple modes of transmission. The present study elucidates the ways that cholinergic neurons could contribute to the elaborate mechanisms involved in olfactory processing in the OB. J. Comp. Neurol. 525:574-591, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Morphological and behavioural changes occur following the X-ray irradiation of the adult mouse olfactory neuroepithelium

    National Research Council Canada - National Science Library

    Cunha, Carla; Hort, Yvonne; Shine, John; Doyle, Kharen L

    2012-01-01

    .... In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes...

  7. Activity-Dependent Dysfunction in Visual and Olfactory Sensory Systems in Mouse Models of Down Syndrome.

    Science.gov (United States)

    William, Christopher M; Saqran, Lubna; Stern, Matthew A; Chiang, Charles L; Herrick, Scott P; Rangwala, Aziz; Albers, Mark W; Frosch, Matthew P; Hyman, Bradley T

    2017-10-11

    Activity-dependent synaptic plasticity plays a critical role in the refinement of circuitry during postnatal development and may be disrupted in conditions that cause intellectual disability, such as Down syndrome (DS). To test this hypothesis, visual cortical plasticity was assessed in Ts65Dn mice that harbor a chromosomal duplication syntenic to human chromosome 21q. We find that Ts65Dn mice demonstrate a defect in ocular dominance plasticity (ODP) following monocular deprivation. This phenotype is similar to that of transgenic mice that express amyloid precursor protein (APP), which is duplicated in DS and in Ts65DN mice; however, normalizing APP gene copy number in Ts65Dn mice fails to rescue plasticity. Ts1Rhr mice harbor a duplication of the telomeric third of the Ts65Dn-duplicated sequence and demonstrate the same ODP defect, suggesting a gene or genes sufficient to drive the phenotype are located in that smaller duplication. In addition, we find that Ts65Dn mice demonstrate an abnormality in olfactory system connectivity, a defect in the refinement of connections to second-order neurons in the olfactory bulb. Ts1Rhr mice do not demonstrate a defect in glomerular refinement, suggesting that distinct genes or sets of genes underlie visual and olfactory system phenotypes. Importantly, these data suggest that developmental plasticity and connectivity are impaired in sensory systems in DS model mice, that such defects may contribute to functional impairment in DS, and that these phenotypes, present in male and female mice, provide novel means for examining the genetic and molecular bases for neurodevelopmental impairment in model mice in vivoSIGNIFICANCE STATEMENT Our understanding of the basis for intellectual impairment in Down syndrome is hindered by the large number of genes duplicated in Trisomy 21 and a lack of understanding of the effect of disease pathology on the function of neural circuits in vivo This work describes early postnatal developmental

  8. Subchronic inhalation exposure to 2-ethyl-1-hexanol impairs the mouse olfactory bulb via injury and subsequent repair of the nasal olfactory epithelium.

    Science.gov (United States)

    Miyake, Mio; Ito, Yuki; Sawada, Masato; Sakai, Kiyoshi; Suzuki, Himiko; Sakamoto, Tatsuo; Sawamoto, Kazunobu; Kamijima, Michihiro

    2016-08-01

    The olfactory system can be a toxicological target of volatile organic compounds present in indoor air. Recently, 2-ethyl-1-hexanol (2E1H) emitted from adhesives and carpeting materials has been postulated to cause "sick building syndrome." Patients' symptoms are associated with an increased sense of smell. This investigation aimed to characterize the histopathological changes of the olfactory epithelium (OE) of the nasal cavity and the olfactory bulb (OB) in the brain, due to subchronic exposure to 2E1H. Male ICR mice were exposed to 0, 20, 60, or 150 ppm 2E1H for 8 h every day for 1 week, or 5 days per week for 1 or 3 months. After a 1-week exposure, the OE showed inflammation and degeneration, with a significant concentration-dependent reduction in the staining of olfactory receptor neurons and in the numbers of globose basal cells at ≥20 ppm. Regeneration occurred at 1 month along with an increase in the basal cells, but lymphocytic infiltration, expanded Bowman's glands, and a decrease in the olfactory receptor neurons were observed at 3 months. Intriguingly, the OB at 3 months showed a reduction in the diameters of the glomeruli and in the number of olfactory nerves and tyrosine hydroxylase-positive neurons, but an increased number of ionized calcium-binding adaptor molecule 1-positive microglia in glomeruli. Accordingly, 2E1H inhalation induced degeneration of the OE with the lowest-observed-adverse-effect level of 20 ppm. The altered number of functional cell components in the OB suggests that effects on olfactory sensation persist after subchronic exposure to 2E1H.

  9. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb.

    Science.gov (United States)

    Bagley, Joshua; LaRocca, Greg; Jimenez, Daniel A; Urban, Nathaniel N

    2007-11-09

    New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ). These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB), ending their migration in the glomerular layer (GLL) and the granule cell layer (GCL) of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA) and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14-40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  10. Adult neurogenesis and specific replacement of interneuron subtypes in the mouse main olfactory bulb

    Directory of Open Access Journals (Sweden)

    LaRocca Greg

    2007-11-01

    Full Text Available Abstract Background New neurons are generated in the adult brain from stem cells found in the subventricular zone (SVZ. These cells proliferate in the SVZ, generating neuroblasts which then migrate to the main olfactory bulb (MOB, ending their migration in the glomerular layer (GLL and the granule cell layer (GCL of the MOB. Neuronal populations in these layers undergo turnover throughout life, but whether all neuronal subtypes found in these areas are replaced and when neurons begin to express subtype-specific markers is not known. Results Here we use BrdU injections and immunohistochemistry against (calretinin, calbindin, N-copein, tyrosine hydroxylase and GABA and show that adult-generated neurons express markers of all major subtypes of neurons in the GLL and GCL. Moreover, the fractions of new neurons that express subtype-specific markers at 40 and 75 days post BrdU injection are very similar to the fractions of all neurons expressing these markers. We also show that many neurons in the glomerular layer do not express NeuN, but are readily and specifically labeled by the fluorescent nissl stain Neurotrace. Conclusion The expression of neuronal subtype-specific markers by new neurons in the GLL and GCL changes rapidly during the period from 14–40 days after BrdU injection before reaching adult levels. This period may represent a critical window for cell fate specification similar to that observed for neuronal survival.

  11. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb

    Directory of Open Access Journals (Sweden)

    Jeffrey E Dahlen

    2011-05-01

    Full Text Available Adult born neurons are added to the olfactory bulb (OB throughout life in rodents. While many factors have been identified as regulating the survival and integration of adult-born neurons (ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic (siRNA knock down of voltage gated sodium channels NaV1.1-1.3 and circuit level (naris occlusion reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock down or naris occlusion. In siRNA knock down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  12. Soft-diet feeding impairs neural transmission between mitral cells and interneurons in the mouse olfactory bulb.

    Science.gov (United States)

    Noguchi, Tomohiro; Utsugi, Chizuru; Kashiwayanagi, Makoto

    2017-11-01

    (Objective) The subventricular zone in mice generates a lot of neuroblasts even during adulthood. These neuroblasts migrate to the olfactory bulb and differentiate into inhibitory interneurons such as granule cells and periglomerular cells. Olfactory sensory neurons receive information from various odorants and transmit it to the olfactory bulb. Our previous study showed that soft-diet feeding impairs neurogenesis in the subventricular zone, in turn leading to the reduction of odor-induced behaviors and Fos-immunoreactivities, the latter of which are markers of neural activity, at the olfactory bulb after exposure to odors. Release of GABA from inhibitory interneurons at the olfactory bulb induces inhibitory currents at the mitral cells, which are output neurons from the olfactory bulb. (Design) In the present study, we measured spontaneous inhibitory postsynaptic currents (sIPSCs) at the mitral cells of mice fed a soft diet in order to explore the effects of changes in texture of diets on neural function at the olfactory bulb. (Results) The soft-diet feeding extended the intervals between sIPSCs and reduced their peak amplitudes. (Conclusions) The present results suggest that soft-diet feeding in mice attenuates the neural functions of inhibitory interneurons at the olfactory bulb. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The effect of metals on spatial memory in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Railey, Angela M; Groeber, Caitlin M; Flinn, Jane M

    2011-01-01

    The amyloid-β protein (Aβ) is a metalloprotein with affinity for the metal ions zinc (Zn), copper (Cu), and iron (Fe), which are found in high concentrations in the plaques of Alzheimer's disease (AD). Increasing attention is focused on the role of these metals in AD, and much of the evidence suggests a dyshomeostasis between these metal ions may significantly affect Aβ aggregation and deposition in the brain. While the effect of these metals on Aβ has been shown in vitro, there is less behavioral data supporting a direct role in cognitive impairment. In order to investigate the cognitive consequences of metal dyshomeostasis, we sought to directly increase metal levels in the brain by dietary means in a transgenic mouse model (Tg2576). We have now examined the effect of increased Zn (10 ppm) and Fe (10 ppm) levels in the drinking water in the Tg2576 mouse. Since increased dietary Zn can lead to Cu deficiency, a Zn group supplemented with copper was also examined (Zn (10 ppm)+Cu (0.025 ppm)). Significant increases in latency and fewer platform crossings on probe trials, which are considered measures of spatial memory impairment, were seen in both Fe and Zn supplemented transgenic mice, compared to those raised on lab water. No significant differences were seen between the Zn + Cu group and in transgenic mice raised on lab water. These data suggest that the negative consequences of Zn may be due to a reduction in copper levels and, therefore, an imbalance between these metal ions rather than a direct effect of increased Zn.

  14. Allosteric Modulation of GABAA Receptors by an Anilino Enaminone in an Olfactory Center of the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Thomas Heinbockel

    2014-12-01

    Full Text Available In an ongoing effort to identify novel drugs that can be used as neurotherapeutic compounds, we have focused on anilino enaminones as potential anticonvulsant agents. Enaminones are organic compounds containing a conjugated system of an amine, an alkene and a ketone. Here, we review the effects of a small library of anilino enaminones on neuronal activity. Our experimental approach employs an olfactory bulb brain slice preparation using whole-cell patch-clamp recording from mitral cells in the main olfactory bulb. The main olfactory bulb is a key integrative center in the olfactory pathway. Mitral cells are the principal output neurons of the main olfactory bulb, receiving olfactory receptor neuron input at their dendrites within glomeruli, and projecting glutamatergic axons through the lateral olfactory tract to the olfactory cortex. The compounds tested are known to be effective in attenuating pentylenetetrazol (PTZ induced convulsions in rodent models. One compound in particular, KRS-5Me-4-OCF3, evokes potent inhibition of mitral cell activity. Experiments aimed at understanding the cellular mechanism underlying the inhibitory effect revealed that KRS-5Me-4-OCF3 shifts the concentration-response curve for GABA to the left. KRS-5Me-4-OCF3 enhances GABA affinity and acts as a positive allosteric modulator of GABAA receptors. Application of a benzodiazepine site antagonist blocks the effect of KRS-5Me-4-OCF3 indicating that KRS-5Me-4-OCF3 binds at the classical benzodiazepine site to exert its pharmacological action. This anilino enaminone KRS-5Me-4-OCF3 emerges as a candidate for clinical use as an anticonvulsant agent in the battle against epileptic seizures.

  15. Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb.

    Science.gov (United States)

    Cheaha, Dania; Bumrungsri, Sara; Chatpun, Surapong; Kumarnsit, Ekkasit

    2015-09-01

    Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been characterized mostly by impaired ultrasonic vocalization, poor sociability and increased repetitive self-grooming behavior. However, its neural signaling remained unknown. This study investigated the local field potentials (LFPs) in the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel open field. VPA was administered at gestational day 13. The results demonstrated three core features of ASD in male offspring. However, there was no difference in Y-maze performance and locomotor activity. Analysis of hippocampal LFP power revealed significantly increased slow wave (1-4 Hz) and high gamma (80-140 Hz) oscillations and decreased theta (4-12 Hz) activity in VPA mice. In the olfactory bulb, VPA animals showed greater slow wave (1-4 Hz) and beta (25-40 Hz) activity and lower activity of low gamma (55-80 Hz) wave. Regression analysis revealed positive correlations between hippocampal theta power and locomotor speed for both control and VPA-exposed mice. There was no significant difference between groups for modulation index of theta (4-12 Hz) phase modulated gamma (30-200 Hz) amplitude. These findings characterized VPA mouse model with LFP oscillations that might provide better understanding of neural processing in ASD. Copyright © 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  16. Roles of GSK3β in odor habituation and spontaneous neural activity of the mouse olfactory bulb.

    Science.gov (United States)

    Xu, Zhixiang; Wang, Li; Chen, Guo; Rao, Xiaoping; Xu, Fuqiang

    2013-01-01

    Glycogen synthase kinase 3β (GSK3β), a multifaceted kinase, is abundantly expressed in the brain, including the olfactory bulb (OB). In resting cells, GSK3β is constitutively active, and its over-activation is presumably involved in numerous brain diseases, such as Alzheimer's disease. However, the functions of the constitutively active GSK3β in the adult brain under physiological conditions are not well understood. Here, we studied the possible functions of GSK3β activity in the OB. Odor stimulation, or blockade of peripheral olfactory inputs caused by either transgenic knock-out or ZnSO4 irrigation to the olfactory epithelium, all affected the expression level of GSK3β in the OB. When GSK3β activity was reduced by a selective inhibitor, the spontaneous oscillatory activity was significantly decreased in the granule cell layer of the OB. Furthermore, local inhibition of GSK3β activity in the OB significantly impaired the odor habituation ability. These results suggest that GSK3β plays important roles in both spontaneous neural activity and odor information processing in the OB, deepening our understanding of the potential functions of the constitutively active GSK3β in the brain under physiological conditions.

  17. Synchronous Infra-Slow Bursting in the Mouse Accessory Olfactory Bulb Emerge from Interplay between Intrinsic Neuronal Dynamics and Network Connectivity.

    Science.gov (United States)

    Zylbertal, Asaph; Yarom, Yosef; Wagner, Shlomo

    2017-03-08

    Rhythmic neuronal activity of multiple frequency bands has been described in many brain areas and attributed to numerous brain functions. Among these, little is known about the mechanism and role of infra-slow oscillations, which have been demonstrated recently in the mouse accessory olfactory bulb (AOB). Along with prolonged responses to stimuli and distinct network connectivity, they inexplicably affect the AOB processing of social relevant stimuli. Here, we show that assemblies of AOB mitral cells are synchronized by lateral interactions through chemical and electrical synapses. Using a network model, we demonstrate that the synchronous oscillations in these assemblies emerge from interplay between intrinsic membrane properties and network connectivity. As a consequence, the AOB network topology, in which each mitral cell receives input from multiple glomeruli, enables integration of chemosensory stimuli over extended time scales by interglomerular synchrony of infra-slow bursting. These results provide a possible functional significance for the distinct AOB physiology and topology. Beyond the AOB, this study presents a general model for synchronous infra-slow bursting in neuronal networks.SIGNIFICANCE STATEMENT Infra-slow rhythmic neuronal activity with a very long (>10 s) duration has been described in many brain areas, but little is known about the role of this activity and the mechanisms that produce it. Here, we combine experimental and computational methods to show that synchronous infra-slow bursting activity in mitral cells of the mouse accessory olfactory bulb (AOB) emerges from interplay between intracellular dynamics and network connectivity. In this novel mechanism, slow intracellular Na+ dynamics endow AOB mitral cells with a weak tendency to burst, which is further enhanced and stabilized by chemical and electrical synapses between them. Combined with the unique topology of the AOB network, infra-slow bursting enables integration and binding of

  18. Pharmacokinetics of [{sup 18}F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Snellman, Anniina; Lopez-Picon, Francisco R.; Haaparanta-Solin, Merja [University of Turku, MediCity/PET Preclinical Laboratory, Turku PET Centre, Turku (Finland); Rokka, Johanna; Eskola, Olli [University of Turku, Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, Turku (Finland); Wilson, Ian; Farrar, Gill [GE Healthcare Medical Diagnostics, Little Chalfont, Buckinghamshire (United Kingdom); Scheinin, Mika [University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Turku University Hospital, Unit of Clinical Pharmacology, Turku (Finland); Solin, Olof [University of Turku, Radiopharmaceutical Chemistry Laboratory, Turku PET Centre, Turku (Finland); Aabo Akademi University, Accelerator Laboratory, Turku PET Centre, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland)

    2012-11-15

    The aim of this study was to investigate the potential of [{sup 18}F]flutemetamol as a preclinical PET tracer for imaging {beta}-amyloid (A{beta}) deposition by comparing its pharmacokinetics to those of [{sup 11}C]Pittsburgh compound B ([{sup 11}C]PIB) in wild-type Sprague Dawley rats and C57Bl/6N mice. In addition, binding of [{sup 18}F]flutemetamol to A{beta} deposits was studied in the Tg2576 transgenic mouse model of Alzheimer's disease. [{sup 18}F]Flutemetamol biodistribution was evaluated using ex vivo PET methods and in vivo PET imaging in wild-type rats and mice. Metabolism and binding of [{sup 11}C]PIB and [{sup 18}F]flutemetamol to plasma proteins were analysed using thin-layer chromatography and ultrafiltration methods, respectively. Radiation dose estimates were calculated from rat ex vivo biodistribution data. The binding of [{sup 18}F]flutemetamol to A{beta} deposits was also studied using ex vivo and in vitro autoradiography. The location of A{beta} deposits in the brain was determined with thioflavine S staining and immunohistochemistry. The pharmacokinetics of [{sup 18}F]flutemetamol resembled that of [{sup 11}C]PIB in rats and mice. In vivo studies showed that both tracers readily entered the brain, and were excreted via the hepatobiliary pathway in both rats and mice. The metabolism of [{sup 18}F]flutemetamol into radioactive metabolites was faster than that of [{sup 11}C]PIB. [{sup 18}F]Flutemetamol cleared more slowly from the brain than [{sup 11}C]PIB, particularly from white matter, in line with its higher lipophilicity. Effective dose estimates for [{sup 11}C]PIB and [{sup 18}F]flutemetamol were 2.28 and 6.65 {mu}Sv/MBq, respectively. Autoradiographs showed [{sup 18}F]flutemetamol binding to fibrillar A{beta} deposits in the brain of Tg2576 mice. Based on its pharmacokinetic profile, [{sup 18}F]flutemetamol showed potential as a PET tracer for preclinical imaging. It showed good brain uptake and was bound to A{beta} deposits in the

  19. Olfactory dreams, olfactory interest, and imagery : Relationships to olfactory memory

    OpenAIRE

    Arshamian, Artin

    2007-01-01

    Existing evidence for olfactory imagery is mixed and mainly based on reports from hallucinations and volitional imagery. Using a questionnaire, Stevenson and Case (2005) showed that olfactory dreams provided a good source for olfactory imagery studies. This study applied an extended version of the same questionnaire and examined olfactory dreams and their relation to real-life experienced odors, volitional imagery, and olfactory interest. Results showed that olfactory dreams were similar to r...

  20. Lack of TRPM5-Expressing Microvillous Cells in Mouse Main Olfactory Epithelium Leads to Impaired Odor-Evoked Responses and Olfactory-Guided Behavior in a Challenging Chemical Environment

    Science.gov (United States)

    Lemons, Kayla; Aoudé, Imad; Ogura, Tatsuya; Mbonu, Kenechukwu; Matsumoto, Ichiro; Arakawa, Hiroyuki

    2017-01-01

    The mammalian main olfactory epithelium (MOE) modifies its activities in response to changes in the chemical environment. This process is essential for maintaining the functions of the olfactory system and the upper airway. However, mechanisms involved in this functional maintenance, especially those occurring via paracrine regulatory pathways within the multicellular MOE, are poorly understood. Previously, a population of non-neuronal, transient receptor potential M5-expressing microvillous cells (TRPM5-MCs) was identified in the MOE, and the initial characterization of these cells showed that they are cholinergic and responsive to various xenobiotics including odorants at high concentrations. Here, we investigated the role of TRPM5-MCs in maintaining olfactory function using transcription factor Skn-1a knockout (Skn-1a-/-) mice, which lack TRPM5-MCs in the MOE. Under our standard housing conditions, Skn-1a-/- mice do not differ significantly from control mice in odor-evoked electro-olfactogram (EOG) responses and olfactory-guided behaviors, including finding buried food and preference reactions to socially and sexually relevant odors. However, after a 2-wk exposure to high-concentration odor chemicals and chitin powder, Skn-1a-/- mice exhibited a significant reduction in their odor and pheromone-evoked EOG responses. Consequently, their olfactory-guided behaviors were impaired compared with vehicle-exposed Skn-1a-/- mice. Conversely, the chemical exposure did not induce significant changes in the EOG responses and olfactory behaviors of control mice. Therefore, our physiological and behavioral results indicate that TRPM5-MCs play a protective role in maintaining the olfactory function of the MOE. PMID:28612045

  1. The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment.

    Science.gov (United States)

    Latchney, Sarah E; Rivera, Phillip D; Mao, Xiao W; Ferguson, Virginia L; Bateman, Ted A; Stodieck, Louis S; Nelson, Gregory A; Eisch, Amelia J

    2014-06-15

    Space missions necessitate physiological and psychological adaptations to environmental factors not present on Earth, some of which present significant risks for the central nervous system (CNS) of crewmembers. One CNS region of interest is the adult olfactory bulb (OB), as OB structure and function are sensitive to environmental- and experience-induced regulation. It is currently unknown how the OB is altered by spaceflight. In this study, we evaluated OB volume and neurogenesis in mice shortly after a 13-day flight on Space Shuttle Atlantis [Space Transport System (STS)-135] relative to two groups of control mice maintained on Earth. Mice housed on Earth in animal enclosure modules that mimicked the conditions onboard STS-135 (AEM-Ground mice) had greater OB volume relative to mice maintained in standard housing on Earth (Vivarium mice), particularly in the granule (GCL) and glomerular (GL) cell layers. AEM-Ground mice also had more OB neuroblasts and fewer apoptotic cells relative to Vivarium mice. However, the AEM-induced increase in OB volume and neurogenesis was not seen in STS-135 mice (AEM-Flight mice), suggesting that spaceflight may have negated the positive effects of the AEM. In fact, when OB volume of AEM-Flight mice was considered, there was a greater density of apoptotic cells relative to AEM-Ground mice. Our findings suggest that factors present during spaceflight have opposing effects on OB size and neurogenesis, and provide insight into potential strategies to preserve OB structure and function during future space missions. Copyright © 2014 the American Physiological Society.

  2. Methods to measure olfactory behavior in mice.

    Science.gov (United States)

    Zou, Junhui; Wang, Wenbin; Pan, Yung-Wei; Lu, Song; Xia, Zhengui

    2015-02-02

    Mice rely on the sense of olfaction to detect food sources, recognize social and mating partners, and avoid predators. Many behaviors of mice, including learning and memory, social interaction, fear, and anxiety are closely associated with their function of olfaction, and behavior tasks designed to evaluate those brain functions may use odors as cues. Accurate assessment of olfaction is not only essential for the study of olfactory system but also critical for proper interpretation of various mouse behaviors, especially learning and memory, emotionality and affect, and sociality. Here we describe a series of behavior experiments that offer multidimensional and quantitative assessments for mouse olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, with respect to both social and nonsocial odors. Copyright © 2015 John Wiley & Sons, Inc.

  3. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. PET imaging of brain with the {beta}-amyloid probe, [{sup 11}C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Toyama, Hiroshi [Fujita Health University, Department of Radiology, Aichi (Japan); National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ye, Daniel; Cohen, Robert M. [National Institutes of Health, Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Ichise, Masanori; Liow, Jeih-San; Cai, Lisheng; Musachio, John L.; Hong, Jinsoo; Crescenzo, Mathew; Tipre, Dnyanesh; Lu, Jian-Qiang; Zoghbi, Sami; Vines, Douglass C.; Pike, Victor W.; Innis, Robert B. [National Institutes of Health, Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland (United States); Jacobowitz, David [USUHS, Department of Anatomy, Physiology, and Genetics, Bethesda, Maryland (United States); Seidel, Jurgen; Green, Michael V. [National Institutes of Health, Department of Nuclear Medicine, Warren Grant Magnuson Clinical Center, Bethesda, Maryland (United States); Katada, Kazuhiro [Fujita Health University, Department of Radiology, Aichi (Japan)

    2005-04-01

    The purpose of this study was to evaluate the capacity of [{sup 11}C]6-OH-BTA-1 and positron emission tomography (PET) to quantify {beta}-amyloid (A{beta}) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0{+-}1.8 months; 23.6{+-}2.6 g) overexpressing a mutated form of human {beta}-amyloid precursor protein (APP) known to result in the production of A{beta} plaques, and in six elderly wild-type litter mates (age 21.8{+-}1.6 months; 29.5{+-}4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [{sup 11}C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. TACs for [{sup 11}C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06{+-}0.04 vs 0.98{+-}0.07, p=0.04; 1.06{+-}0.09 vs 0.93{+-}0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread A{beta} plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild

  5. Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease.

    Science.gov (United States)

    Velazquez, Ramon; Tran, An; Ishimwe, Egide; Denner, Larry; Dave, Nikhil; Oddo, Salvatore; Dineley, Kelly T

    2017-10-01

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Assessment of Olfactory Memory in Olfactory Dysfunction.

    Science.gov (United States)

    Kollndorfer, Kathrin; Reichert, Johanna; Braunsteiner, Josephine; Schöpf, Veronika

    2017-01-01

    To assess all clinically relevant components of olfactory perception, examinations for olfactory sensitivity, discrimination, and identification are performed. Besides the standard perceptual test battery, episodic olfactory memory might offer additional information about olfactory abilities relative to these standard clinical tests. As both olfactory deficits and memory deficits are early symptoms in neurodegenerative disorders, olfactory memory may be of particular interest. However, to date little is known about episodic olfactory memory performance in patients with decreased olfactory function. This study includes the investigation of olfactory memory performance in 14 hyposmic patients (8 female, mean age 52.6 years) completing two episodic odor memory tests (Sniffin' Test of Odor Memory and Odor Memory Test). To control for a general impairment in memory function, a verbal and a figural memory test were carried out. A regression model with multiple predictors was calculated for both odor memory tests separately. Odor identification was identified as the only significant predictor for both odor memory tasks. From our results, we conclude that currently available olfactory memory tests are highly influenced by odor identification abilities, implying the need for the development and validation of additional tests in this field which could serve as additional olfactory perception variables for clinical assessment.

  7. Olfactory G proteins: simple and complex signal transduction.

    Science.gov (United States)

    Ebrahimi, F A; Chess, A

    1998-06-04

    In both vertebrates and invertebrates, olfactory perception is mediated by G-protein-coupled receptors. Recent work, in both mouse and Caenorhabditis elegans, sheds light on the role of specific G proteins in olfactory signal transduction, neuronal morphology and axon guidance.

  8. TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction

    NARCIS (Netherlands)

    Ragancokova, D.; Rocca, E.; Oonk, A.M.M.; Schulz, H.; Rohde, E.; Bednarsch, J.; Feenstra, I.; Pennings, R.J.E.; Wende, H.; Garratt, A.N.

    2014-01-01

    The olfactory bulb (OB) receives odor information from the olfactory epithelium and relays this to the olfactory cortex. Using a mouse model, we found that development and maturation of OB interneurons depends on the zinc finger homeodomain factor teashirt zinc finger family member 1 (TSHZ1). In

  9. Properties of an optogenetic model for olfactory stimulation

    Science.gov (United States)

    Thews, Marion; Möhrlen, Frank; Frings, Stephan

    2016-01-01

    Key points In olfactory research it is difficult to deliver stimuli with defined intensity and duration to olfactory sensory neurons.Expression of channelrhodopsin 2 (ChR2) in olfactory sensory neurons provides a means to activate these neurons with light flashes. Appropriate mouse models are available.The present study explores the suitability of an established olfactory marker protein (OMP)/ChR2–yellow fluorescent protein (YFP) mouse model for ex vivo experimentation.Expression of ChR2 in sensory neurons of the main olfactory epithelium, the septal organ and vomeronasal organ is characterized. Expression pattern of ChR2 in olfactory receptor neurons and the properties of light responses indicate that light stimulation does not impact on signal transduction in the chemosensory cilia.Light‐induced electro‐olfactograms are characterized with light flashes of different intensities, durations and frequencies.The impact of light‐induced afferent stimulation on the olfactory bulb is examined with respect to response amplitude, polarity and low‐pass filtering. Abstract For the examination of sensory processing, it is helpful to deliver stimuli in precisely defined temporal and spatial patterns with accurate control of stimulus intensity. This is challenging in experiments with the mammalian olfactory system because airborne odorants have to be transported into the intricate sensory structures of the nose and must dissolve in mucus to be detected by sensory neurons. Defined and reproducible activity can be generated in olfactory sensory neurons that express the light‐gated ion channel channelrhodopsin 2 (ChR2). The neurons can be stimulated by light flashes in a controlled fashion by this optogenetic approach. Here we examined the application of an olfactory marker protein (OMP)/ChR2–yellow fluorescent protein (YFP) model for ex vivo exploration of the olfactory epithelium and the olfactory bulb of the mouse. We studied the expression patterns of ChR2 in the

  10. Notch1 activity in the olfactory bulb is odour-dependent and contributes to olfactory behaviour.

    Science.gov (United States)

    Brai, Emanuele; Marathe, Swananda; Zentilin, Lorena; Giacca, Mauro; Nimpf, Johannes; Kretz, Robert; Scotti, Alessandra; Alberi, Lavinia

    2014-11-01

    Notch signalling plays an important role in synaptic plasticity, learning and memory functions in both Drosophila and rodents. In this paper, we report that this feature is not restricted to hippocampal networks but also involves the olfactory bulb (OB). Odour discrimination and olfactory learning in rodents are essential for survival. Notch1 expression is enriched in mitral cells of the mouse OB. These principal neurons are responsive to specific input odorants and relay the signal to the olfactory cortex. Olfactory stimulation activates a subset of mitral cells, which show an increase in Notch activity. In Notch1cKOKln mice, the loss of Notch1 in mitral cells affects the magnitude of the neuronal response to olfactory stimuli. In addition, Notch1cKOKln mice display reduced olfactory aversion to propionic acid as compared to wildtype controls. This indicates, for the first time, that Notch1 is involved in olfactory processing and may contribute to olfactory behaviour. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. The location of olfactory receptors within olfactory epithelium is independent of odorant volatility and solubility

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    DeFazio Anthony R

    2011-05-01

    Full Text Available Abstract Background Our objective was to study the pattern of olfactory receptor expression within the dorsal and ventral regions of the mouse olfactory epithelium. We hypothesized that olfactory receptors were distributed based on the chemical properties of their ligands: e.g. receptors for polar, hydrophilic and weakly volatile odorants would be present in the dorsal region of olfactory epithelium; while receptors for non-polar, more volatile odorants would be distributed to the ventral region. To test our hypothesis, we used micro-transplantation of cilia-enriched plasma membranes derived from dorsal or ventral regions of the olfactory epithelium into Xenopus oocytes for electrophysiological characterization against a panel of 100 odorants. Findings Odorants detected by ORs from the dorsal and ventral regions showed overlap in volatility and water solubility. We did not find evidence for a correlation between the solubility and volatility of odorants and the functional expression of olfactory receptors in the dorsal or ventral region of the olfactory epithelia. Conclusions No simple clustering or relationship between chemical properties of odorants could be associated with the different regions of the olfactory epithelium. These results suggest that the location of ORs within the epithelium is not organized based on the physico-chemical properties of their ligands.

  12. Ciliary neurotrophic factor cell-based delivery prevents synaptic impairment and improves memory in mouse models of Alzheimer's disease.

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    Garcia, Pierre; Youssef, Ihsen; Utvik, Jo K; Florent-Béchard, Sabrina; Barthélémy, Vanassa; Malaplate-Armand, Catherine; Kriem, Badreddine; Stenger, Christophe; Koziel, Violette; Olivier, Jean-Luc; Escanye, Marie-Christine; Hanse, Marine; Allouche, Ahmad; Desbène, Cédric; Yen, Frances T; Bjerkvig, Rolf; Oster, Thierry; Niclou, Simone P; Pillot, Thierry

    2010-06-02

    The development of novel therapeutic strategies for Alzheimer's disease (AD) represents one of the biggest unmet medical needs today. Application of neurotrophic factors able to modulate neuronal survival and synaptic connectivity is a promising therapeutic approach for AD. We aimed to determine whether the loco-regional delivery of ciliary neurotrophic factor (CNTF) could prevent amyloid-beta (Abeta) oligomer-induced synaptic damages and associated cognitive impairments that typify AD. To ensure long-term administration of CNTF in the brain, we used recombinant cells secreting CNTF encapsulated in alginate polymers. The implantation of these bioreactors in the brain of Abeta oligomer-infused mice led to a continuous secretion of recombinant CNTF and was associated with the robust improvement of cognitive performances. Most importantly, CNTF led to full recovery of cognitive functions associated with the stabilization of synaptic protein levels in the Tg2576 AD mouse model. In vitro as well as in vivo, CNTF activated a Janus kinase/signal transducer and activator of transcription-mediated survival pathway that prevented synaptic and neuronal degeneration. These preclinical studies suggest that CNTF and/or CNTF receptor-associated pathways may have AD-modifying activity through protection against progressive Abeta-related memory deficits. Our data also encourage additional exploration of ex vivo gene transfer for the prevention and/or treatment of AD.

  13. Centella asiatica Extract Improves Behavioral Deficits in a Mouse Model of Alzheimer's Disease: Investigation of a Possible Mechanism of Action

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    Amala Soumyanath

    2012-01-01

    Full Text Available Centella asiatica (CA, commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD, we examined the effects of a water extract of CA (GKW in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.

  14. Fus1 KO mouse as a model of oxidative stress-mediated sporadic Alzheimer’s disease: circadian disruption and long-term spatial and olfactory memory impairments.

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    Guillermo Coronas-Samano

    2016-11-01

    Full Text Available Insufficient advances in the development of effective therapeutic treatments of sporadic Alzheimer's Disease (sAD to date are largely due to the lack of sAD-relevant animal models. While the vast majority of models do recapitulate AD's hallmarks of plaques and tangles by virtue of tau and/or beta amyloid overexpression, these models do not reflect the fact that in sAD (unlike familial AD these genes are not risk factors per se and that other mechanisms like oxidative stress, metabolic dysregulation and inflammation play key roles in AD etiology. Here we characterize and propose the Fus1 KO mice that lack a mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance, we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old, the equivalent human age when the earliest cognitive and olfactory sAD symptoms arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased levels of PRDX1, disruption of metabolic homeostasis (decreased levels of ACC2, increased phosphorylation of AMPK, autophagy (decreased levels of LC3-II, PKC (decreased levels of RACK1 and calcium signaling (decreased levels of Calb2 in the olfactory bulb and/or hippocampus. Mice were behaviorally tested using objective and accurate video tracking (Noldus, in which Fus1 KO mice showed clear deficits in olfactory memory (decreased habituation/cross-habituation in the short and long term, olfactory guided navigation memory (inability to reduce their latency to find the hidden cookie, spatial memory (learning impairments on finding the platform in the Morris water maze and showed more sleep time during the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory perception (cross-habituation, association memory (passive avoidance or in species-typical behavior (nest building and no increased anxiety (open field, light-dark box or depression/anhedonia (sucrose preference at this relatively young age. These

  15. Conditional Deletion ofRic-8bin Olfactory Sensory Neurons Leads to Olfactory Impairment.

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    Machado, Cleiton F; Nagai, Maíra H; Lyra, Cassandra S; Reis-Silva, Thiago M; Xavier, André M; Glezer, Isaias; Felicio, Luciano F; Malnic, Bettina

    2017-12-13

    The olfactory system can discriminate a vast number of odorants. This ability derives from the existence of a large family of odorant receptors expressed in the cilia of the olfactory sensory neurons. Odorant receptors signal through the olfactory-specific G-protein subunit, Gαolf. Ric-8b, a guanine nucleotide exchange factor, interacts with Gαolf and can amplify odorant receptor signal transduction in vitro To explore the function of Ric-8b in vivo , we generated a tissue specific knock-out mouse by crossing OMP-Cre transgenic mice to Ric-8b floxed mice. We found that olfactory-specific Ric-8b knock-out mice of mixed sex do not express the Gαolf protein in the olfactory epithelium. We also found that in these mice, the mature olfactory sensory neuron layer is reduced, and that olfactory sensory neurons show increased rate of cell death compared with wild-type mice. Finally, behavioral tests showed that the olfactory-specific Ric-8b knock-out mice show an impaired sense of smell, even though their motivation and mobility behaviors remain normal. SIGNIFICANCE STATEMENT Ric-8b is a guanine nucleotide exchange factor (GEF) expressed in the olfactory epithelium and in the striatum. Ric-8b interacts with the olfactory Gαolf subunit, and can amplify odorant signaling through odorant receptors in vitro However, the functional significance of this GEF in the olfactory neurons in vivo remains unknown. We report that deletion of Ric-8b in olfactory sensory neurons prevents stable expression of Gαolf. In addition, we demonstrate that olfactory neurons lacking Ric-8b (and consequently Gαolf) are more susceptible to cell death. Ric-8b conditional knock-out mice display impaired olfactory guided behavior. Our results reveal that Ric-8b is essential for olfactory function, and suggest that it may also be essential for Gαolf-dependent functions in the brain. Copyright © 2017 the authors 0270-6474/17/3712202-12$15.00/0.

  16. Olfactory Neuroblastoma: Diagnostic Difficulty

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    Vidya MN,

    2011-01-01

    Full Text Available Olfactory neuroblastoma is an uncommon malignant tumor of sinonasal tract arising from the olfactory neuro epithelium. The olfactory neuroblastomas presenting with divergent histomorphologies like, epithelial appearance of cells, lacking a neuro fibrillary background and absence of rosettes are difficult to diagnose. Such cases require immunohistochemistry to establish the diagnosis. We describe the clinical features, pathological and immunohistochemical findings of grade IV Olfactory neuroblastoma in a 57 year old man

  17. An IP3R3- and NPY-expressing microvillous cell mediates tissue homeostasis and regeneration in the mouse olfactory epithelium.

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    Cuihong Jia

    Full Text Available Calcium-dependent release of neurotrophic factors plays an important role in the maintenance of neurons, yet the release mechanisms are understudied. The inositol triphosphate (IP3 receptor is a calcium release channel that has a physiological role in cell growth, development, sensory perception, neuronal signaling and secretion. In the olfactory system, the IP3 receptor subtype 3 (IP3R3 is expressed exclusively in a microvillous cell subtype that is the predominant cell expressing neurotrophic factor neuropeptide Y (NPY. We hypothesized that IP3R3-expressing microvillous cells secrete sufficient NPY needed for both the continual maintenance of the neuronal population and for neuroregeneration following injury. We addressed this question by assessing the release of NPY and the regenerative capabilities of wild type, IP3R3(+/-, and IP3R3(-/- mice. Injury, simulated using extracellular ATP, induced IP3 receptor-mediated NPY release in wild-type mice. ATP-evoked NPY release was impaired in IP3R3(-/- mice, suggesting that IP3R3 contributes to NPY release following injury. Under normal physiological conditions, both IP3R3(-/- mice and explants from these mice had fewer progenitor cells that proliferate and differentiate into immature neurons. Although the number of mature neurons and the in vivo rate of proliferation were not altered, the proliferative response to the olfactotoxicant satratoxin G and olfactory bulb ablation injury was compromised in the olfactory epithelium of IP3R3(-/- mice. The reductions in both NPY release and number of progenitor cells in IP3R3(-/- mice point to a role of the IP3R3 in tissue homeostasis and neuroregeneration. Collectively, these data suggest that IP3R3 expressing microvillous cells are actively responsive to injury and promote recovery.

  18. Endogenous siRNAs and noncoding RNA-derived small RNAs are expressed in adult mouse hippocampus and are up-regulated in olfactory discrimination training.

    OpenAIRE

    Smalheiser, Neil; Lugli, G.; Thimmapuram, Jyothi; Cook, E H; Larson, J.

    2010-01-01

    We previously proposed that endogenous siRNAs may regulate synaptic plasticity and long-term gene expression in the mammalian brain. Here, a hippocampal-dependent task was employed in which adult mice were trained to execute a nose-poke in a port containing one of two simultaneously present odors in order to obtain a reward. Mice demonstrating olfactory discrimination training were compared to pseudo-training and nose-poke control groups; size-selected hippocampal RNA was subjected to Illumin...

  19. Minocycline restores olfactory bulb volume and olfactory behavior after traumatic brain injury in mice.

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    Siopi, Eleni; Calabria, Silvia; Plotkine, Michel; Marchand-Leroux, Catherine; Jafarian-Tehrani, Mehrnaz

    2012-01-20

    Permanent olfactory dysfunction can often arise after traumatic brain injury (TBI) and while one of the main causes is the immediate loss of neurons in the olfactory bulb (OB), the emergent neuroinflammatory environment following TBI may further promote OB deterioration. Therefore, we examined the effects of acute anti-inflammatory treatment with minocycline on post-TBI olfactory behavior and on OB surface. The mouse model of closed-head injury by mechanical percussion was applied to anesthetized Swiss mice. The treatment protocol included three injections of minocycline (i.p.) at 5 min (90 mg/kg), 3 h, and 9 h (45 mg/kg) post-TBI. An olfactory avoidance test was run up to 12 weeks post-TBI. The mice were then sacrificed and their OB surface was measured. Our results demonstrated a post-TBI olfactory behavior deficit that was significant up to at least 12 weeks post-TBI. Additionally, substantial post-TBI OB atrophy was observed that was strongly correlated with the behavioral impairment. Minocycline was able to attenuate both the olfactory lesions and corresponding functional deficit in the short and long term. These results emphasize the potential role of minocycline as a promising neuroprotective agent for the treatment of TBI-related olfactory bulb lesions and deficits.

  20. Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease.

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    Anna Parachikova

    2010-11-01

    Full Text Available Dietary supplements have been extensively studied for their beneficial effects on cognition and AD neuropathology. The current study examines the effect of a medical food cocktail consisting of the dietary supplements curcumin, piperine, epigallocatechin gallate, α-lipoic acid, N-acetylcysteine, B vitamins, vitamin C, and folate on cognitive functioning and the AD hallmark features and amyloid-beta (Aβ in the Tg2576 mouse model of the disease.The study found that administering the medical food cocktail for 6 months improved cortical- and hippocampal- dependent learning in the transgenic mice, rendering their performance indistinguishable from non-transgenic controls. Coinciding with this improvement in learning and memory, we found that treatment resulted in decreased soluble Aβ, including Aβ oligomers, previously found to be linked to cognitive functioning.In conclusion, the current study demonstrates that combination diet consisting of natural dietary supplements improves cognitive functioning while decreasing AD neuropathology and may thus represent a safe, natural treatment for AD.

  1. Mini-review: Making scent of the presence and local translation of odorant receptor mRNAs in olfactory axons

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    Dubacq, Caroline; Fouquet, Coralie; Trembleau, Alain

    2016-01-01

    Rodents contain in their genome more than 1,000 functional odorant receptor genes, which are specifically expressed by the olfactory sensory neurons projecting from the olfactory epithelium to the olfactory bulb. Strong evidence for the presence and local translation of odorant receptor mRNAs in the axon of olfactory sensory neurons was obtained, but no function has been assigned to these axonal mRNAs yet. The aim of this review is to discuss the evidence for the presence and local translation of odorant receptor mRNAs in olfactory sensory axons, and to speculate on their possible function in the wiring of the mouse olfactory sensory projections. PMID:23959692

  2. Valproic acid ameliorates olfactory dysfunction in APP/PS1 transgenic mice of Alzheimer's disease: Ameliorations from the olfactory epithelium to the olfactory bulb.

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    Yao, Zhi-Gang; Jing, Hai-Yan; Wang, Dong-Mei; Lv, Bei-Bei; Li, Jia-Mei; Liu, Feng-Feng; Fan, Hui; Sun, Xi-Chao; Qin, Ye-Jun; Zhao, Miao-Qing

    2016-05-01

    Olfactory dysfunction is a common and early symptom of many neurodegenerative diseases, particularly of Alzheimer's disease (AD) and mild cognitive impairment, pointing to the progression to dementia. Recent studies have revealed that valproic acid (VPA) has neuroprotective effects in rodent models of AD. In this study, we investigated the effects of VPA on olfactory dysfunction of APP/PS1 double transgenic mouse models of AD. After continuous treatment with a 100mg/kg daily dose of VPA for 3 months, APP/PS1 mice showed improved olfactory performances. In agreement with the behavioral findings, VPA treatment reduced amyloid β (Aβ) burden in the olfactory epithelium (OE) of transgenic mice. And, VPA increased epithelial thickness of the olfactory mucosa through decreased cell apoptosis and increased cell proliferation. In the olfactory bulb (OB), VPA administration also reduced senile plaques and levels of soluble and insoluble Aβ42 peptides. Besides, VPA promoted the increase of mitral cells and decrease of neurofilament immunostaining. In hence, VPA treatment completely improved the olfactory performances and prevented degenerative changes of the OE and OB. Our study raises the possibility of AD diagnosis by OE biopsy. Moreover, VPA may provide a novel therapeutic strategy for the treatment of olfactory dysfunction in AD patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Centrifugal telencephalic afferent connections to the main and accessory olfactory bulbs

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    Mohedano-Moriano, Alicia; de la Rosa-Prieto, Carlos; Saiz-Sanchez, Daniel; Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; de Moya-Pinilla, Miguel; Martinez-Marcos, Alino

    2012-01-01

    Parallel to the olfactory system, most mammals possess an accessory olfactory or vomeronasal system. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs, which in turn project to adjacent areas of the telencephalon, respectively. New data indicate that projections arising from the main and accessory olfactory bulbs partially converge in the rostral telencephalon and are non-overlapping at caudal telencephalic levels. Therefore, the basal telencephalon should be reclassified in olfactory, vomeronasal, and mixed areas. On the other hand, it has been demonstrated that virtually all olfactory- and vomeronasal-recipient structures send reciprocal projections to the main and accessory olfactory bulbs, respectively. Further, non-chemosensory recipient structures also projects centrifugally to the olfactory bulbs. These feed-back projections appear to be essential modulating processing of chemosensory information. The present work aims at characterizing centrifugal projections to the main and accessory olfactory bulbs arising from olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic areas. This issue has been addressed by using tracer injections in the rat and mouse brain. Tracer injections were delivered into the main and accessory olfactory bulbs as well as in olfactory, vomeronasal, mixed, and non-chemosensory recipient telencephalic structures. The results confirm that olfactory- and vomeronasal-recipient structures project to the main and accessory olfactory bulbs, respectively. Interestingly, olfactory (e.g., piriform cortex), vomeronasal (e.g., posteromedial cortical amygdala), mixed (e.g., the anterior medial amygdaloid nucleus), and non-chemosensory-recipient (e.g., the nucleus of the diagonal band) structures project to the main and to the accessory olfactory bulbs thus providing the possibility of simultaneous modulation and interaction of both systems at different stages of chemosensory processing

  4. Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels-An Ex Vivo Study.

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    Śmieszek, Agnieszka; Stręk, Zuzanna; Kornicka, Katarzyna; Grzesiak, Jakub; Weiss, Christine; Marycz, Krzysztof

    2017-04-20

    Metformin, the popular anti-diabetic drug was shown to exert multiple biological effects. The most recent metformin gained attention as an agent that mobilizes endogenous progenitor cells and enhances regenerative potential of organisms, for example by promoting neurogenesis. In the present study, we examined the role of metformin on mouse olfactory ensheathing cells (mOECs) derived from animals receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The mOECs expanded ex vivo were characterized in terms of their cellular phenotype, morphology, proliferative activity, viability and accumulation of oxidative stress factors. Moreover, we determined the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), distinguishing the secretion of BDNF by mOECs in cultures and circulating serum levels of BDNF. The mOECs used in the experiment were glial fibrillary acidic protein (GFAP) and p75 neurotrophin receptor (p75 NTR ) positive and exhibited both astrocyte-like and non-myelin Schwann cell-like morphologies. Our results revealed that the proliferation of OECs derived from mice treated with metformin was lowered, when compared to control group. Simultaneously, we noted increased cell viability, reduced expression of markers associated with cellular senescence and a decreased amount of reactive oxygen species. We observed increased mRNA expression of BDNF and its down-stream genes. Obtained results indicate that metformin may exert antioxidant, anti-apoptotic and senolytic action on OECs expanded ex vivo.

  5. Antioxidant and Anti-Senescence Effect of Metformin on Mouse Olfactory Ensheathing Cells (mOECs) May Be Associated with Increased Brain-Derived Neurotrophic Factor Levels—An Ex Vivo Study

    Science.gov (United States)

    Śmieszek, Agnieszka; Stręk, Zuzanna; Kornicka, Katarzyna; Grzesiak, Jakub; Weiss, Christine; Marycz, Krzysztof

    2017-01-01

    Metformin, the popular anti-diabetic drug was shown to exert multiple biological effects. The most recent metformin gained attention as an agent that mobilizes endogenous progenitor cells and enhances regenerative potential of organisms, for example by promoting neurogenesis. In the present study, we examined the role of metformin on mouse olfactory ensheathing cells (mOECs) derived from animals receiving metformin for eight weeks at a concentration equal to 2.8 mg/day. The mOECs expanded ex vivo were characterized in terms of their cellular phenotype, morphology, proliferative activity, viability and accumulation of oxidative stress factors. Moreover, we determined the mRNA and protein levels of brain-derived neurotrophic factor (BDNF), distinguishing the secretion of BDNF by mOECs in cultures and circulating serum levels of BDNF. The mOECs used in the experiment were glial fibrillary acidic protein (GFAP) and p75 neurotrophin receptor (p75NTR) positive and exhibited both astrocyte-like and non-myelin Schwann cell-like morphologies. Our results revealed that the proliferation of OECs derived from mice treated with metformin was lowered, when compared to control group. Simultaneously, we noted increased cell viability, reduced expression of markers associated with cellular senescence and a decreased amount of reactive oxygen species. We observed increased mRNA expression of BDNF and its down-stream genes. Obtained results indicate that metformin may exert antioxidant, anti-apoptotic and senolytic action on OECs expanded ex vivo. PMID:28425952

  6. Endogenous siRNAs and noncoding RNA-derived small RNAs are expressed in adult mouse hippocampus and are up-regulated in olfactory discrimination training.

    Science.gov (United States)

    Smalheiser, Neil R; Lugli, Giovanni; Thimmapuram, Jyothi; Cook, Edwin H; Larson, John

    2011-01-01

    We previously proposed that endogenous siRNAs may regulate synaptic plasticity and long-term gene expression in the mammalian brain. Here, a hippocampal-dependent task was employed in which adult mice were trained to execute a nose-poke in a port containing one of two simultaneously present odors in order to obtain a reward. Mice demonstrating olfactory discrimination training were compared to pseudo-training and nose-poke control groups; size-selected hippocampal RNA was subjected to Illumina deep sequencing. Sequences that aligned uniquely and exactly to the genome without uncertain nucleotide assignments, within exons or introns of MGI annotated genes, were examined further. The data confirm that small RNAs having features of endogenous siRNAs are expressed in brain; that many of them derive from genes that regulate synaptic plasticity (and have been implicated in neuropsychiatric diseases); and that hairpin-derived endo-siRNAs and the 20- to 23-nt size class of small RNAs show a significant increase during an early stage of training. The most abundant putative siRNAs arose from an intronic inverted repeat within the SynGAP1 locus; this inverted repeat was a substrate for dicer in vitro, and SynGAP1 siRNA was specifically associated with Argonaute proteins in vivo. Unexpectedly, a dramatic increase with training (more than 100-fold) was observed for a class of 25- to 30-nt small RNAs derived from specific sites within snoRNAs and abundant noncoding RNAs (Y1 RNA, RNA component of mitochondrial RNAse P, 28S rRNA, and 18S rRNA). Further studies are warranted to characterize the role(s) played by endogenous siRNAs and noncoding RNA-derived small RNAs in learning and memory.

  7. Olfactory ensheathing glia are required for embryonic olfactory axon targeting and the migration of gonadotropin-releasing hormone neurons

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    Perrine Barraud

    2013-06-01

    Kallmann's syndrome is caused by the failure of olfactory axons and gonadotropin-releasing hormone (GnRH neurons to enter the embryonic forebrain, resulting in anosmia and sterility. Sox10 mutations have been associated with Kallmann's syndrome phenotypes, but their effect on olfactory system development is unknown. We recently showed that Sox10 is expressed by neural crest-derived olfactory ensheathing cells (OECs. Here, we demonstrate that in homozygous Sox10lacZ/lacZ mouse embryos, OEC differentiation is disrupted; olfactory axons accumulate in the ventromedial olfactory nerve layer and fewer olfactory receptor neurons express the maturation marker OMP (most likely owing to the failure of axonal targeting. Furthermore, GnRH neurons clump together in the periphery and a smaller proportion enters the forebrain. Our data suggest that human Sox10 mutations cause Kallmann's syndrome by disrupting the differentiation of OECs, which promote embryonic olfactory axon targeting and hence olfactory receptor neuron maturation, and GnRH neuron migration to the forebrain.

  8. Progranulin gene delivery reduces plaque burden and synaptic atrophy in a mouse model of Alzheimer's disease.

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    Van Kampen, Jackalina M; Kay, Denis G

    2017-01-01

    Progranulin (PGRN) is a multifunctional protein that is widely expressed throughout the brain, where it has been shown to act as a critical regulator of CNS inflammation and also functions as an autocrine neuronal growth factor, important for long-term neuronal survival. PGRN has been shown to activate cell signaling pathways regulating excitoxicity, oxidative stress, and synaptogenesis, as well as amyloidogenesis. Together, these critical roles in the CNS suggest that PGRN has the potential to be an important therapeutic target for the treatment of various neurodegenerative disorders, particularly Alzheimer's disease (AD). AD is the leading cause of dementia and is marked by the appearance of extracellular plaques consisting of aggregates of amyloid-β (Aβ), as well as neuroinflammation, oxidative stress, neuronal loss and synaptic atrophy. The ability of PGRN to target multiple key features of AD pathophysiology suggests that enhancing its expression may benefit this disease. Here, we describe the application of PGRN gene transfer using in vivo delivery of lentiviral expression vectors in a transgenic mouse model of AD. Viral vector delivery of the PGRN gene effectively enhanced PGRN expression in the hippocampus of Tg2576 mice. This elevated PGRN expression significantly reduced amyloid plaque burden in these mice, accompanied by reductions in markers of inflammation and synaptic atrophy. The overexpression of PGRN was also found to increase activity of neprilysin, a key amyloid beta degrading enzyme. PGRN regulation of neprilysin activity could play a major role in the observed alterations in plaque burden. Thus, PGRN may be an effective therapeutic target for the treatment of AD.

  9. α7 Nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model.

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    Tiina Maria Pirttimaki

    Full Text Available It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ, the toxic trigger for Alzheimer's disease (AD, interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs. Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT. The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.

  10. Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

    Science.gov (United States)

    Trushina, Eugenia; Nemutlu, Emirhan; Zhang, Song; Christensen, Trace; Camp, Jon; Mesa, Janny; Siddiqui, Ammar; Tamura, Yasushi; Sesaki, Hiromi; Wengenack, Thomas M.; Dzeja, Petras P.; Poduslo, Joseph F.

    2012-01-01

    Background The identification of early mechanisms underlying Alzheimer's Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated

  11. Expression of olfactory signaling genes in the eye.

    Directory of Open Access Journals (Sweden)

    Alexey Pronin

    Full Text Available To advance our understanding how the outer eye interacts with its environment, we asked which cellular receptors are expressed in the cornea, focusing on G protein-coupled receptors.Total RNA from the mouse cornea was subjected to next-generation sequencing using the Illumina platform. The data was analyzed with TopHat and CuffLinks software packages. Expression of a representative group of genes detected by RNA-seq was further analyzed by RT-PCR and in situ hybridization using RNAscope technology and fluorescent microscopy.We generated more than 46 million pair-end reads from mouse corneal RNA. Bioinformatics analysis revealed that the mouse corneal transcriptome reconstructed from these reads represents over 10,000 gene transcripts. We identified 194 GPCR transcripts, of which 96 were putative olfactory receptors. RT-PCR analysis confirmed the presence of several olfactory receptors and related genes, including olfactory marker protein and the G protein associated with olfaction, Gαolf. In situ hybridization showed that mRNA for olfactory marker protein, Gαolf and possibly some olfactory receptors were found in the corneal epithelial cells. In addition to the corneal epithelium, Gαolf was present in the ganglionic and inner nuclear layers of the retina. One of the olfactory receptors, Olfr558, was present primarily in vessels of the eye co-stained with antibodies against alpha-smooth muscle actin, indicating expression in arterioles.Several species of mRNA encoding putative olfactory receptors and related genes are expressed in the mouse cornea and other parts of the eye indicating they may play a role in sensing chemicals in the ocular environment.

  12. Expressing exogenous functional odorant receptors in cultured olfactory sensory neurons

    Directory of Open Access Journals (Sweden)

    Fomina Alla F

    2008-09-01

    Full Text Available Abstract Background Olfactory discrimination depends on the large numbers of odorant receptor genes and differential ligand-receptor signaling among neurons expressing different receptors. In this study, we describe an in vitro system that enables the expression of exogenous odorant receptors in cultured olfactory sensory neurons. Olfactory sensory neurons in the culture express characteristic signaling molecules and, therefore, provide a system to study receptor function within its intrinsic cellular environment. Results We demonstrate that cultured olfactory sensory neurons express endogenous odorant receptors. Lentiviral vector-mediated gene transfer enables successful ectopic expression of odorant receptors. We show that the ectopically expressed mouse I7 is functional in the cultured olfactory sensory neurons. When two different odorant receptors are ectopically expressed simultaneously, both receptor proteins co-localized in the same olfactory sensory neurons up to 10 days in vitro. Conclusion This culture technique provided an efficient method to culture olfactory sensory neurons whose morphology, molecular characteristics and maturation progression resembled those observed in vivo. Using this system, regulation of odorant receptor expression and its ligand specificity can be studied in its intrinsic cellular environment.

  13. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  14. OLAF: standardization of international olfactory tests.

    Science.gov (United States)

    Hummel, C; Zucco, G M; Iannilli, E; Maboshe, W; Landis, B N; Hummel, T

    2012-03-01

    Developed in the 1990 s, the "Sniffin 'Sticks" test for the assessment of olfactory threshold, odor identification and discrimination has become a widely used tool both in clinical and research settings. Originally pencil-and-paper documented, it may now be applied using a computer program. The "Filemaker" based software "OLAF" guides the examiner through any user-defined arrangement of the test battery, stores all data in a database, and offers results sheets to be printed out for convenience. The royalty-free program may be downloaded from http://www.tu-dresden.de/medkhno/riechen_schmecken/olaf.zip as a runtime solution application. It is currently available in four languages (English, French, German, and Italian) which can be toggled by a single mouse click, and is suitable for Windows as well as Apple platforms. In conclusion, the currently described software is expected to further facilitate and standardize olfactory testing with the "Sniffin' Sticks" test battery.

  15. Preserved Fronto-Striatal Plasticity and Enhanced Procedural Learning in a Transgenic Mouse Model of Alzheimer's Disease Overexpressing Mutant "hAPPswe"

    Science.gov (United States)

    Middei, Silvia; Geracitano, Raffaella; Caprioli, Antonio; Mercuri, Nicola; Ammassari-Teule, Martine

    2004-01-01

    Mutations in the amyloid precursor protein (APP) gene inducing abnormal processing and deposition of [beta]-amyloid protein in the brain have been implicated in the pathogenesis of Alzheimer's disease (AD). Although Tg2576 mice with the Swedish mutation ("hAPPswe") exhibit age-related [Alpha][beta]-plaque formation in brain regions like the…

  16. Functional evidence of multidrug resistance transporters (MDR in rodent olfactory epithelium.

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    Adrien Molinas

    Full Text Available P-glycoprotein (Pgp and multidrug resistance-associated protein (MRP1 are membrane transporter proteins which function as efflux pumps at cell membranes and are considered to exert a protective function against the entry of xenobiotics. While evidence for Pgp and MRP transporter activity is reported for olfactory tissue, their possible interaction and participation in the olfactory response has not been investigated.Functional activity of putative MDR transporters was assessed by means of the fluorometric calcein acetoxymethyl ester (calcein-AM accumulation assay on acute rat and mouse olfactory tissue slices. Calcein-AM uptake was measured as fluorescence intensity changes in the presence of Pgp or MRP specific inhibitors. Epifluorescence microscopy measured time course analysis in the olfactory epithelium revealed significant inhibitor-dependent calcein uptake in the presence of each of the selected inhibitors. Furthermore, intracellular calcein accumulation in olfactory receptor neurons was also significantly increased in the presence of either one of the Pgp or MRP inhibitors. The presence of Pgp or MRP1 encoding genes in the olfactory mucosa of rat and mouse was confirmed by RT-PCR with appropriate pairs of species-specific primers. Both transporters were expressed in both newborn and adult olfactory mucosa of both species. To assess a possible involvement of MDR transporters in the olfactory response, we examined the electrophysiological response to odorants in the presence of the selected MDR inhibitors by recording electroolfactograms (EOG. In both animal species, MRPs inhibitors induced a marked reduction of the EOG magnitude, while Pgp inhibitors had only a minor or no measurable effect.The findings suggest that both Pgp and MRP transporters are functional in the olfactory mucosa and in olfactory receptor neurons. Pgp and MRPs may be cellular constituents of olfactory receptor neurons and represent potential mechanisms for modulation

  17. Olfactory Dysfunctions and Decreased Nitric Oxide Production in the Brain of Human P301L Tau Transgenic Mice.

    Science.gov (United States)

    Hu, Yang; Ding, Wenting; Zhu, Xiaonan; Chen, Ruzhu; Wang, Xuelan

    2016-04-01

    Different patterns of olfactory dysfunction have been found in both patients and mouse models of Alzheimer's Disease. However, the underlying mechanism of the dysfunction remained unknown. Deficits of nitric oxide production in brain can cause olfactory dysfunction by preventing the formation of olfactory memory. The aim of this study was to investigate the behavioral changes in olfaction and alterations in metabolites of nitric oxide, nitrate/nitrite concentration, in the brain of human P301L tau transgenic mice. The tau mice showed impairments in olfaction and increased abnormal phosphorylation of Tau protein at AT8 in different brain areas, especially in olfactory bulb. We now report that these olfactory deficits and Tau pathological changes were accompanied by decreased nitrate/nitrite concentration in the brain, especially in the olfactory bulb, and reduced expression of nNOS in the brain of tau mice. These findings provided evidence of olfactory dysfunctions correlated with decreased nitric oxide production in the brain of tau mice.

  18. A ventral glomerular deficit in Parkinson's disease revealed by whole olfactory bulb reconstruction.

    Science.gov (United States)

    Zapiec, Bolek; Dieriks, Birger V; Tan, Sheryl; Faull, Richard L M; Mombaerts, Peter; Curtis, Maurice A

    2017-10-01

    Olfactory dysfunction is common in Parkinson's disease and is an early symptom, but its pathogenesis remains poorly understood. Hindering progress in our mechanistic understanding of olfactory dysfunction in Parkinson's disease is the paucity of literature about the human olfactory bulb, both from normal and Parkinson's disease cases. Qualitatively it is well established that the neat arrangement of the glomerular array seen in the mouse olfactory bulb is missing in humans. But rigorous quantitative approaches to describe and compare the thousands of glomeruli in the human olfactory bulb are not available. Here we report a quantitative approach to describe the glomerular component of the human olfactory bulb, and its application to draw statistical comparisons between olfactory bulbs from normal and Parkinson's disease cases. We subjected horizontal 10 µm sections of olfactory bulbs from six normal and five Parkinson's disease cases to fluorescence immunohistochemistry with antibodies against vesicular glutamate transporter-2 and neural cell adhesion molecule. We scanned the immunostained sections with a fluorescence slide scanner, segmented the glomeruli, and generated 3D reconstructions of whole olfactory bulbs. We document the occurrence of atypical glomerular morphologies and glomerular-like structures deep in the olfactory bulb, both in normal and Parkinson's disease cases. We define a novel and objective parameter: the global glomerular voxel volume, which is the total volume of all voxels that are classified immunohistochemically as glomerular. We find that the global glomerular voxel volume in Parkinson's disease cases is half that of normal cases. The distribution of glomerular voxels along the dorsal-ventral dimension of the olfactory bulb in these series of horizontal sections is significantly altered in Parkinson's disease cases: whereas most glomerular voxels reside within the ventral half of olfactory bulbs from normal cases, glomerular voxels are

  19. Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.

    Science.gov (United States)

    Wang, Wenbin; Lu, Song; Li, Tan; Pan, Yung-Wei; Zou, Junhui; Abel, Glen M; Xu, Lihong; Storm, Daniel R; Xia, Zhengui

    2015-05-20

    Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury. Copyright © 2015 the authors 0270-6474/15/357833-17$15.00/0.

  20. Olfactory deficits in Niemann-Pick type C1 (NPC1 disease.

    Directory of Open Access Journals (Sweden)

    Marina Hovakimyan

    Full Text Available BACKGROUND: Niemann-Pick type C disease (NPC is a rare autosomal recessive lipid storage disease characterized by progressive neurodegeneration. As only a few studies have been conducted on the impact of NPC on sensory systems, we used a mutant mouse model (NPC1(-/- to examine the effects of this disorder to morphologically distinct regions of the olfactory system, namely the olfactory epithelium (OE and olfactory bulb (OB. METHODOLOGY/PRINCIPAL FINDINGS: For structural and functional analysis immunohistochemistry, electron microscopy, western blotting, and electrophysiology have been applied. For histochemistry and western blotting, we used antibodies against a series of neuronal and glia marker proteins, as well as macrophage markers. NPC1(-/- animals present myelin-like lysosomal deposits in virtually all types of cells of the peripheral and central olfactory system. Especially supporting cells of the OE and central glia cells are affected, resulting in pronounced astrocytosis and microgliosis in the OB and other olfactory cortices. Up-regulation of Galectin-3, Cathepsin D and GFAP in the cortical layers of the OB underlines the critical role and location of the OB as a possible entrance gate for noxious substances. Unmyelinated olfactory afferents of the lamina propria seem less affected than ensheathing cells. Supporting the structural findings, electro-olfactometry of the olfactory mucosa suggests that NPC1(-/- animals exhibit olfactory and trigeminal deficits. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a pronounced neurodegeneration and glia activation in the olfactory system of NPC1(-/-, which is accompanied by sensory deficits.

  1. [Olfactory bulb volume in patients with posttraumatic olfactory dysfunction].

    Science.gov (United States)

    Liu, H; Hang, W; Liu, G; Han, T

    2017-04-07

    Objective: To analyze the correlation between olfactory bulb(OB) volume and olfactory function in patients with posttraumatic olfactory dysfunction. Methods: Forty patients with posttraumatic olfactory dysfunction were compared with forty controls in terms of olfactory function T&T testing, OB volume assessed with magnetic resonance imaging (MRI). SPSS 17.0 software was used to analyze the data. Results: T&T olfactory testing revealed that patients with posttraumatic olfactory dysfunction had higher scores than controls(3.47±0.63 vs.1.39±0.19, t=4.317, Polfactory dysfunction were affected by the same extent of olfactory loss(3.52±0.66 vs.3.43±0.61, t=0.896, P>0.05). Both men and women as controls were affected by the same extent of olfactory loss(1.41±0.20 vs.1.38±0.17, t=1.073, P>0.05). OB volume of left side in patients with posttraumatic olfactory dysfunction were (36.15±3.16)mm(3,) right side were (39.28±3.76)mm(3,) average OB volume were (37.55±3.42)mm(3;) OB volume of left side in controls were (81.74±5.87)mm(3,) right side were (83.58±6.13)mm(3,) average OB volume were (82.59±5.99)mm(3;) OB volumes were lower in patients with posttraumatic olfactory dysfunction as compared with controls(t value were 4.815, 4.837 and 4.825, all Polfactory discriminate threshold was negatively correlated with average OB volume in posttraumatic olfactory dysfunction and controls(r value was-0.582, -0.564, both Polfactory discriminate threshold was positively correlated with impairment degree in patients with posttraumatic olfactory dysfunction(r value was 0.472, Polfactory dysfunction(r value was -0.397, Polfactory dysfunction as compared with controls. The OB volume is correlated with olfactory function. Impairment degree in patients with posttraumatic olfactory dysfunction is accordance with olfactory function lowering degree. Megnetic resonance imaging can be used as a supplementary diagnostic tool for patients with posttraumatic olfactory dysfunction.

  2. Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex

    Science.gov (United States)

    Mori, Kensaku; Manabe, Hiroyuki; Narikiyo, Kimiya; Onisawa, Naomi

    2013-01-01

    The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness may require neuronal circuit mechanisms for the “binding” of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron—olfactory bulb—olfactory cortex—orbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex. PMID:24137148

  3. An Olfactory Subsystem that Mediates High-Sensitivity Detection of Volatile Amines

    Directory of Open Access Journals (Sweden)

    Rodrigo Pacifico

    2012-07-01

    Full Text Available Olfactory stimuli are detected by over 1,000 odorant receptors in mice, with each receptor being mapped to specific glomeruli in the olfactory bulb. The trace amine-associated receptors (TAARs are a small family of evolutionarily conserved olfactory receptors whose contribution to olfaction remains enigmatic. Here, we show that a majority of the TAARs are mapped to a discrete subset of glomeruli in the dorsal olfactory bulb of the mouse. This TAAR projection is distinct from the previously described class I and class II domains, and is formed by a sensory neuron population that is restricted to express TAAR genes prior to choice. We also show that the dorsal TAAR glomeruli are selectively activated by amines at low concentrations. Our data uncover a hard-wired, parallel input stream in the main olfactory pathway that is specialized for the detection of volatile amines.

  4. Can we smell without an olfactory bulb?

    Science.gov (United States)

    Rombaux, Philippe; Mouraux, André; Bertrand, Bernard; Duprez, Thierry; Hummel, Thomas

    2007-01-01

    Lack of an olfactory bulb (OB) is typically associated with anosmia. We present a patient with subnormal olfactory function in whom the OB could not be detected with magnetic resonance imaging (MRI). Olfactory function was evaluated on two occasions. Orthonasal olfactory function was assessed with the "Sniffin' Sticks" test providing a score equivalent to hyposmia. Retronasal olfactory function was studied with "smell powders" indicating a decreased, but not absence of, olfactory function. Importantly, chemosensory event-related potentials were clearly present in response to olfactory and trigeminal stimuli. This indicates that olfactory function may be present in some subjects even when an OB can not be detected with MRI.

  5. Are olfactory receptors really olfactive?

    DEFF Research Database (Denmark)

    Giorgi, Franco; Maggio, Roberto; Bruni, Luis Emilio

    2011-01-01

    Any living organism interacts with and responds specifically to environmental molecules by expressing specific olfactory receptors. This specificity will be first examined in causal terms with particular emphasis on the mechanisms controlling olfactory gene expression, cell-to-cell interactions a...

  6. Prognostic value of olfactory bulb volume measurement for recovery in postinfectious and posttraumatic olfactory loss.

    Science.gov (United States)

    Rombaux, Philippe; Huart, Caroline; Deggouj, Naima; Duprez, Thierry; Hummel, Thomas

    2012-12-01

    Several prognostic factors influencing the recovery from olfactory dysfunction have been described. The aim of this study was to investigate whether olfactory bulb volume could be used as a new predictor of olfactory recovery in postinfectious and posttraumatic olfactory loss. Cohort study; Level of evidence, 4. Setting Tertiary university clinic, department of otolaryngology. A cohort of 60 patients with postinfectious (n = 28) and posttraumatic olfactory loss (n = 32) was investigated. Assessment of olfactory function was performed using orthonasal (Sniffin' Sticks test) and retronasal psychophysical olfactory tests, at the time of the diagnosis (t1) and 15 months later (t2). All patients were examined on 3 tesla magnetic resonance imaging, and the olfactory bulbs volume was assessed using planimetric contouring at the time of the diagnosis (t1). Recovery rate was 25% in patients with posttraumatic olfactory loss and 36% in patients with postinfectious olfactory loss. There was a correlation between both orthonasal and retronasal olfactory testing and the initial measurement of the total olfactory bulb volume. In addition, we observed a significant correlation between changes in olfactory functions and initial measurement of the total olfactory bulb volume, with larger volumes relating to higher improvement of olfactory function. Finally, we found that none of the patients with a total olfactory bulb volume of 40 mm(3) or less exhibited recovery of olfactory function. Olfactory bulb volume seems to be a predictor of olfactory recovery in patients with postinfectious and posttraumatic olfactory loss.

  7. Olfactory dysfunction in neuromyelitis optica spectrum disorders

    NARCIS (Netherlands)

    Zhang, L.J.; Zhao, N.; Fu, Y.; Zhang, D.Q.; Wang, J.; Qin, W.; Zhang, N.N.N.; Wood, K.; Liu, Y.; Yu, C.S.; Shi, F.D.; Yang, L.

    2015-01-01

    Few data were available for the understanding of olfactory function in neuromyelitis optica spectrum disorders (NMOSDs). The aims of our study were to investigate the incidence of olfactory dysfunction and characterize olfactory structures, using MRI, in patients with NMOSDs. Olfactory function was

  8. An early dysregulation of FAK and MEK/ERK signaling pathways precedes the β-amyloid deposition in the olfactory bulb of APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Lachén-Montes, Mercedes; González-Morales, Andrea; de Morentin, Xabier Martínez; Pérez-Valderrama, Estela; Ausín, Karina; Zelaya, María Victoria; Serna, Antonio; Aso, Ester; Ferrer, Isidro; Fernández-Irigoyen, Joaquín; Santamaría, Enrique

    2016-10-04

    Olfactory dysfunction is an early event of Alzheimer's disease (AD). However, the mechanisms associated to AD neurodegeneration in olfactory areas are unknown. Here we used double-transgenic amyloid precursor protein/presenilin 1 (APPswe/PS1dE9) mice and label-free quantitative proteomics to analyze early pathological effects on the olfactory bulb (OB) during AD progression. Prior to β-amyloid plaque formation, 9 modulated proteins were detected on 3-month-old APP/PS1 mice while 16 differential expressed proteins were detected at 6months, when β-amyloid plaques appear, indicating a moderate imbalance in cytoskeletal rearrangement, and synaptic plasticity in APP/PS1 OBs. Moreover, β-amyloid induced an inactivation of focal adhesion kinase (FAK) together with a transient activation of MEK1/2, leading to inactivation of ERK1/2 in 6-months APP/PS1 OBs. In contrast, the analysis of human OBs revealed a late activation of FAK in advanced AD stages, whereas ERK1/2 activation was enhanced across AD staging respect to controls. This survival potential was accompanied by the inhibition of the proapototic factor BAD in the OB across AD phenotypes. Our data contribute to a better understanding of the early molecular mechanisms that are modulated in AD neurodegeneration, highlighting significant differences in the regulation of survival pathways between APP/PS1 mice and sporadic human AD. Loss of smell is involved in early stages of Alzheimer's disease (AD), usually preceding classic disease symptoms. However, the mechanisms governing this dysfunction are still poorly understood, losing its potential as a useful tool for clinical diagnosis. Our study characterizes potential AD-associated molecular changes in APP/PS1 mice olfactory bulb (OB) using MS-quantitative proteomics, revealing early cytoskeletal disruption and synaptic plasticity impairment. Moreover, an opposite pattern was found when comparing the activation status of specific survival pathways between APP/PS1 OBs

  9. Predators are attracted to the olfactory signals of prey

    National Research Council Canada - National Science Library

    Hughes, Nelika K; Price, Catherine J; Banks, Peter B

    2010-01-01

    .... Yet while most territorial mammals communicate using olfactory signals and olfactory hunting is widespread in predators, evidence for the attraction of predators to prey olfactory signals under field...

  10. Melatonin in the mammalian olfactory bulb

    OpenAIRE

    Corthell, J.T.; Olcese, J.; Trombley, P.Q.

    2013-01-01

    Melatonin is a neurohormone associated with circadian rhythms. A diurnal rhythm in olfactory sensitivity has been previously reported and melatonin receptor mRNAs have been observed in the olfactory bulb, but the effects of melatonin in the olfactory bulb have not been explored. First, we corroborated data from a previous study that identified melatonin receptor messenger RNAs in the olfactory bulb. We then investigated whether melatonin treatment would affect cells in the olfactory bulbs of ...

  11. Olfactory Behaviour in Farm Animals

    NARCIS (Netherlands)

    Clouard, C.M.; Bolhuis, J.E.

    2017-01-01

    This chapter presents several examples of how olfactory information and farming conditions affects the behaviour of farm animals and presents opportunities to improve the welfare and production of farm animals by making use of odours and olfaction.

  12. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice.

    Science.gov (United States)

    Akers, Katherine G; Kushner, Steven A; Leslie, Ana T; Clarke, Laura; van der Kooy, Derek; Lerch, Jason P; Frankland, Paul W

    2011-07-07

    Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

  13. Activity-induced remodeling of olfactory bulb microcircuits revealed by monosynaptic tracing.

    Directory of Open Access Journals (Sweden)

    Benjamin R Arenkiel

    Full Text Available The continued addition of new neurons to mature olfactory circuits represents a remarkable mode of cellular and structural brain plasticity. However, the anatomical configuration of newly established circuits, the types and numbers of neurons that form new synaptic connections, and the effect of sensory experience on synaptic connectivity in the olfactory bulb remain poorly understood. Using in vivo electroporation and monosynaptic tracing, we show that postnatal-born granule cells form synaptic connections with centrifugal inputs and mitral/tufted cells in the mouse olfactory bulb. In addition, newly born granule cells receive extensive input from local inhibitory short axon cells, a poorly understood cell population. The connectivity of short axon cells shows clustered organization, and their synaptic input onto newborn granule cells dramatically and selectively expands with odor stimulation. Our findings suggest that sensory experience promotes the synaptic integration of new neurons into cell type-specific olfactory circuits.

  14. Olfactory bulb volume in smokers.

    Science.gov (United States)

    Schriever, Valentin A; Reither, Nicole; Gerber, Johannes; Iannilli, Emilia; Hummel, Thomas

    2013-03-01

    The study aimed to investigate the volume of the olfactory bulb in smokers. Specifically, we wanted to see whether environmental influences may exert a negative influence on OB structure. Twenty-one smokers and 59 non-smokers, matched for age and sex, underwent olfactory testing by means of the Sniffin' Sticks testing device (measurement of odor threshold and identification abilities). In addition, they underwent an MR scan with 2-mm-thick T2-weighted fast spin-echo images without interslice gap in the coronal plane covering the anterior and middle segments of the base of the skull. Olfactory function was not different between the 2 groups; however, olfactory bulb volumes were smaller in smokers than in non-smokers (p = 0.006). The deficit seen at the level of the OB did not correlate with the duration of smoking. The current data indicate that smoking may have a negative effect on the olfactory system before this becomes obvious in terms of a decreased olfactory function.

  15. Olfactory Systems in Mate Recognition and Sexual Behavior

    NARCIS (Netherlands)

    Keller, M.; Pillon, D.; Bakker, J.

    2010-01-01

    Olfactory signals play an important role so that breeding efforts are synchronized with appropriate social and environmental circumstances. In this context, the mammalian olfactory system is characterized by the existence of several olfactory subsystems that have evolved to process olfactory

  16. Predators are attracted to the olfactory signals of prey.

    Directory of Open Access Journals (Sweden)

    Nelika K Hughes

    2010-09-01

    Full Text Available Predator attraction to prey social signals can force prey to trade-off the social imperatives to communicate against the profound effect of predation on their future fitness. These tradeoffs underlie theories on the design and evolution of conspecific signalling systems and have received much attention in visual and acoustic signalling modes. Yet while most territorial mammals communicate using olfactory signals and olfactory hunting is widespread in predators, evidence for the attraction of predators to prey olfactory signals under field conditions is lacking.To redress this fundamental issue, we examined the attraction of free-roaming predators to discrete patches of scents collected from groups of two and six adult, male house mice, Mus domesticus, which primarily communicate through olfaction. Olfactorily-hunting predators were rapidly attracted to mouse scent signals, visiting mouse scented locations sooner, and in greater number, than control locations. There were no effects of signal concentration on predator attraction to their prey's signals.This implies that communication will be costly if conspecific receivers and eavesdropping predators are simultaneously attracted to a signal. Significantly, our results also suggest that receivers may be at greater risk of predation when communicating than signallers, as receivers must visit risky patches of scent to perform their half of the communication equation, while signallers need not.

  17. Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.

    LENUS (Irish Health Repository)

    Mitchell, Jacqueline C

    2010-01-01

    X11alpha is a neuronal-specific adaptor protein that binds to the amyloid-beta protein precursor (AbetaPP). Overexpression of X11alpha reduces Abeta production but whether X11alpha also protects against Abeta-related memory dysfunction is not known. To test this possibility, we crossed X11alpha transgenic mice with AbetaPP-Tg2576 mice. AbetaPP-Tg2576 mice produce high levels of brain Abeta and develop age-related defects in memory function that correlate with increasing Abeta load. Overexpression of X11alpha alone had no detectable adverse effect upon behavior. However, X11alpha reduced brain Abeta levels and corrected spatial reference memory defects in aged X11alpha\\/AbetaPP double transgenics. Thus, X11alpha may be a therapeutic target for Alzheimer\\'s disease.

  18. [Olfactory sensory perception].

    Science.gov (United States)

    Fuentes, Aler; Fresno, María Javiera; Santander, Hugo; Valenzuela, Saúl; Gutiérrez, Mario Felipe; Miralles, Rodolfo

    2011-03-01

    The five senses have had a fundamental importance for survival and socialization of human beings. From an evolutionary point of view the sense of smell is the oldest. This sense has a strong representation within the genome, allowing the existence of many types of receptors that allow us to capture multiple volatile odor producing molecules, sending electrical signals to higher centers to report the outside world. Several cortical areas are activated in the brain, which are interconnected to form an extensive and complex neural network, linking for example, areas involved with memory and emotions, thus giving this sense of perceptual richness. While the concept of flavor is largely related to the sense of taste, smell provides the necessary integration with the rest of the senses and higher functions. Fully understanding the sense of smell is relevant to health professionals. Knowing the characteristics of the receptors, the transduction processes and convergence of information in the higher centers involved, we can properly detect olfactory disorders in our patients.

  19. TRPM5-expressing microvillous cells in the main olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Liman Emily R

    2008-11-01

    Full Text Available Abstract Background The main olfactory epithelium (MOE in the nasal cavity detects a variety of air borne molecules that provide information regarding the presence of food, predators and other relevant social and environmental factors. Within the epithelium are ciliated sensory neurons, supporting cells, basal cells and microvillous cells, each of which is distinct in morphology and function. Arguably, the least understood, are the microvillous cells, a population of cells that are small in number and whose function is not known. We previously found that in a mouse strain in which the TRPM5 promoter drives expression of the green fluorescent protein (GFP, a population of ciliated olfactory sensory neurons (OSNs, as well as a population of cells displaying microvilli-like structures is labeled. Here we examined the morphology and immunocytochemical properties of these microvillous-like cells using immunocytochemical methods. Results We show that the GFP-positive microvillous cells were morphologically diversified and scattered throughout the entire MOE. These cells immunoreacted to an antibody against TRPM5, confirming the expression of this ion channel in these cells. In addition, they showed a Ca2+-activated non-selective cation current in electrophysiological recordings. They did not immunoreact to antibodies that label cell markers and elements of the transduction pathways from olfactory sensory neurons and solitary chemosensory cells of the nasal cavity. Further, the TRPM5-expressing cells did not display axon-like processes and were not labeled with a neuronal marker nor did trigeminal peptidergic nerve fibers innervate these cells. Conclusion We provide morphological and immunocytochemical characterization of the TRPM5-expressing microvillous cells in the main olfactory epithelium. Our data demonstrate that these cells are non-neuronal and in terms of chemosensory transduction do not resemble the TRPM5-expressing olfactory sensory neurons

  20. Olfaction in three genetic and two MPTP-induced Parkinson's disease mouse models.

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    Stefan Kurtenbach

    Full Text Available Various genetic or toxin-induced mouse models are frequently used for investigation of early PD pathology. Although olfactory impairment is known to precede motor symptoms by years, it is not known whether it is caused by impairments in the brain, the olfactory epithelium, or both. In this study, we investigated the olfactory function in three genetic Parkinson's disease (PD mouse models and mice treated with MPTP intraperitoneally and intranasally. To investigate olfactory function, we performed electro-olfactogram recordings (EOGs and an olfactory behavior test (cookie-finding test. We show that neither a parkin knockout mouse strain, nor intraperitoneal MPTP treated animals display any olfactory impairment in EOG recordings and the applied behavior test. We also found no difference in the responses of the olfactory epithelium to odorants in a mouse strain over-expressing doubly mutated α-synuclein, while this mouse strain was not suitable to test olfaction in a cookie-finding test as it displays a mobility impairment. A transgenic mouse expressing mutated α-synuclein in dopaminergic neurons performed equal to control animals in the cookie-finding test. Further we show that intranasal MPTP application can cause functional damage of the olfactory epithelium.

  1. A novel brain receptor is expressed in a distinct population of olfactory sensory neurons

    NARCIS (Netherlands)

    Conzelmann, S; Levai, O; Bode, B; Eisel, U; Raming, K; Breer, H; Strotmann, J

    2000-01-01

    Three novel G-protein-coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a

  2. Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling

    OpenAIRE

    Vincis; Lagier; van de Ville; Rodriguez; Carleton

    2015-01-01

    Summary Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS) imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely ...

  3. Sniffing and Oxytocin: Effects on Olfactory Memories.

    Science.gov (United States)

    Stoop, Ron

    2016-05-04

    In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Awlad-Thani, Kathyia; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

    2015-01-01

    At present, the treatment options available to delay the onset or slow down the progression of Alzheimer's disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1-40 and 1-42) in plasma of control and experimental animals. Standard diet-fed Tg mice showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild-type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the

  5. Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

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    Hong Sjölinder

    Full Text Available Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

  6. Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

    Science.gov (United States)

    Sjölinder, Hong; Jonsson, Ann-Beth

    2010-01-01

    Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS) is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival. PMID:21124975

  7. Contribution of pheromones processed by the main olfactory system to mate recognition in female mammals

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    Micheal J. Baum

    2012-06-01

    Full Text Available Until recently it was widely believed that the ability of female mammals (with the likely exception of women to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female’s vomeronasal organ and their subsequent processing by a neural circuit that includes the accessory olfactory bulb, vomeronasal amygdala, and hypothalamus. Emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the main olfactory epithelium of female mice which, in turn, leads to the activation of a population of glomeruli and abutting mitral cells in the main olfactory bulb (MOB. Anatomical results along with functional neuroanatomical data demonstrate that some of these MOB mitral cells project to the vomeronasal amygdala. These particular MOB mitral cells were selectively activated (i.e., expressed Fos protein by exposure to male as opposed to female urinary volatiles. A similar selectivity to opposite sex urinary volatiles was also seen in mitral cells of the accessory olfactory bulb of female mice. Behavioral data from female mouse, ferret, and human are reviewed that implicate the main olfactory system, in some cases interacting with the accessory olfactory system, in mate recognition.

  8. The Stimulus-Dependent Gradient of Cyp26B1+ Olfactory Sensory Neurons Is Necessary for the Functional Integrity of the Olfactory Sensory Map.

    Science.gov (United States)

    Login, Hande; Håglin, Sofia; Berghard, Anna; Bohm, Staffan

    2015-10-07

    Stimulus-dependent expression of the retinoic acid-inactivating enzyme Cyp26B1 in olfactory sensory neurons (OSNs) forms a dorsomedial (DM)-ventrolateral (VL) gradient in the mouse olfactory epithelium. The gradient correlates spatially with different rates of OSN turnover, as well as the functional organization of the olfactory sensory map, into overlapping zones of OSNs that express different odorant receptors (ORs). Here, we analyze transgenic mice that, instead of a stimulus-dependent Cyp26B1 gradient, have constitutive Cyp26B1 levels in all OSNs. Starting postnatally, OSN differentiation is decreased and progenitor proliferation is increased. Initially, these effects are selective to the VL-most zone and correlate with reduced ATF5 expression and accumulation of OSNs that do not express ORs. Transcription factor ATF5 is known to stabilize OR gene choice via onset of the stimulus-transducing enzyme adenylyl cyclase type 3. During further postnatal development of Cyp26B1 mice, an anomalous DM(high)-VL(low) expression gradient of adenylyl cyclase type 3 appears, which coincides with altered OR frequencies and OR zones. All OR zones expand ventrolaterally except for the VL-most zone, which contracts. The expansion results in an increased zonal overlap that is also evident in the innervation pattern of OSN axon terminals in olfactory bulbs. These findings together identify a mechanism by which postnatal sensory-stimulated vitamin A metabolism modifies the generation of spatially specified neurons and their precise topographic connectivity. The distributed patterns of vitamin A-metabolizing enzymes in the nervous system suggest the possibility that the mechanism may also regulate neuroplasticity in circuits other than the olfactory sensory map. The mouse olfactory sensory map is functionally wired according to precise axonal projections of spatially organized classes of olfactory sensory neurons in the nose. The genetically controlled mechanisms that regulate the

  9. Role of a ubiquitously expressed receptor in the vertebrate olfactory system.

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    DeMaria, Shannon; Berke, Allison P; Van Name, Eric; Heravian, Anisa; Ferreira, Todd; Ngai, John

    2013-09-18

    Odorant cues are recognized by receptors expressed on olfactory sensory neurons, the primary sensory neurons of the olfactory epithelium. Odorant receptors typically obey the "one receptor, one neuron" rule, in which the receptive field of the olfactory neuron is determined by the singular odorant receptor that it expresses. Odor-evoked receptor activity across the population of olfactory neurons is then interpreted by the brain to identify the molecular nature of the odorant stimulus. In the present study, we characterized the properties of a C family G-protein-coupled receptor that, unlike most other odorant receptors, is expressed in a large population of microvillous sensory neurons in the zebrafish olfactory epithelium and the mouse vomeronasal organ. We found that this receptor, OlfCc1 in zebrafish and its murine ortholog Vmn2r1, is a calcium-dependent, low-sensitivity receptor specific for the hydrophobic amino acids isoleucine, leucine, and valine. Loss-of-function experiments in zebrafish embryos demonstrate that OlfCc1 is required for olfactory responses to a diverse mixture of polar, nonpolar, acidic, and basic amino acids. OlfCc1 was also found to promote localization of other OlfC receptor family members to the plasma membrane in heterologous cells. Together, these results suggest that the broadly expressed OlfCc1 is required for amino acid detection by the olfactory system and suggest that it plays a role in the function and/or intracellular trafficking of other olfactory and vomeronasal receptors with which it is coexpressed.

  10. Gene Expression Profiles of Main Olfactory Epithelium in Adenylyl Cyclase 3 Knockout Mice

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    Zhenshan Wang

    2015-11-01

    Full Text Available Adenylyl Cyclase 3 (AC3 plays an important role in the olfactory sensation-signaling pathway in mice. AC3 deficiency leads to defects in olfaction. However, it is still unknown whether AC3 deficiency affects gene expression or olfactory signal transduction pathways within the main olfactory epithelium (MOE. In this study, gene microarrays were used to screen differentially expressed genes in MOE from AC3 knockout (AC3−/− and wild-type (AC3+/+ mice. The differentially expressed genes identified were subjected to bioinformatic analysis and verified by qRT-PCR. Gene expression in the MOE from AC3−/− mice was significantly altered, compared to AC3+/+ mice. Of the 41266 gene probes, 3379 had greater than 2-fold fold change in expression levels between AC3−/− and AC3+/+ mice, accounting for 8% of the total gene probes. Of these genes, 1391 were up regulated, and 1988 were down regulated, including 425 olfactory receptor genes, 99 genes that are specifically expressed in the immature olfactory neurons, 305 genes that are specifically expressed in the mature olfactory neurons, and 155 genes that are involved in epigenetic regulation. Quantitative RT-PCR verification of the differentially expressed epigenetic regulation related genes, olfactory receptors, ion transporter related genes, neuron development and differentiation related genes, lipid metabolism and membrane protein transport etc. related genes showed that P75NTR, Hinfp, Gadd45b, and Tet3 were significantly up-regulated, while Olfr370, Olfr1414, Olfr1208, Golf, Faim2, Tsg101, Mapk10, Actl6b, H2BE, ATF5, Kirrrel2, OMP, Drd2 etc. were significantly down-regulated. In summary, AC3 may play a role in proximal olfactory signaling and play a role in the regulation of differentially expressed genes in mouse MOE.

  11. Olfactory training in patients with Parkinson's disease.

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    Antje Haehner

    Full Text Available OBJECTIVE: Decrease of olfactory function in Parkinson's disease (PD is a well-investigated fact. Studies indicate that pharmacological treatment of PD fails to restore olfactory function in PD patients. The aim of this investigation was whether patients with PD would benefit from "training" with odors in terms of an improvement of their general olfactory function. It has been hypothesized that olfactory training should produce both an improved sensitivity towards the odors used in the training process and an overall increase of olfactory function. METHODS: We recruited 70 subjects with PD and olfactory loss into this single-center, prospective, controlled non-blinded study. Thirty-five patients were assigned to the olfactory training group and 35 subjects to the control group (no training. Olfactory training was performed over a period of 12 weeks while patients exposed themselves twice daily to four odors (phenyl ethyl alcohol: rose, eucalyptol: eucalyptus, citronellal: lemon, and eugenol: cloves. Olfactory testing was performed before and after training using the "Sniffin' Sticks" (thresholds for phenyl ethyl alcohol, tests for odor discrimination, and odor identification in addition to threshold tests for the odors used in the training process. RESULTS: Compared to baseline, trained PD patients experienced a significant increase in their olfactory function, which was observed for the Sniffin' Sticks test score and for thresholds for the odors used in the training process. Olfactory function was unchanged in PD patients who did not perform olfactory training. CONCLUSION: The present results indicate that olfactory training may increase olfactory sensitivity in PD patients.

  12. Subtype-specific reduction of olfactory bulb interneurons in Pax6 heterozygous mutant mice.

    Science.gov (United States)

    Haba, Hasumi; Nomura, Tadashi; Suto, Fumikazu; Osumi, Noriko

    2009-09-01

    Interneurons in the olfactory bulb (OB) play essential roles in the processing of olfactory information. They are classified into several subpopulations by the expression of different neurochemical markers. Here we focused on a transcription factor Pax6, and examined its expression and function in distinct subtypes of OB interneurons. We identified Pax6 expression in specific subtypes of interneurons in the external plexiform layer (EPL). The number of these interneuron subtypes was dramatically decreased in Pax6 heterozygous mutant mice. These results indicate that Pax6 is required for differentiation and/or maintenance of EPL interneurons in the adult mouse OB.

  13. Immunohistochemical characterization of human olfactory tissue.

    Science.gov (United States)

    Holbrook, Eric H; Wu, Enming; Curry, William T; Lin, Derrick T; Schwob, James E

    2011-08-01

    The pathophysiology underlying human olfactory disorders is poorly understood because biopsying the olfactory epithelium (OE) can be unrepresentative and extensive immunohistochemical analysis is lacking. Autopsy tissue enriches our grasp of normal and abnormal olfactory immunohistology and guides the sampling of the OE by biopsy. Furthermore, a comparison of the molecular phenotype of olfactory epithelial cells between rodents and humans will improve our ability to correlate human histopathology with olfactory dysfunction. An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies. Human olfactory mucosa obtained from 21 autopsy specimens was analyzed with immunohistochemistry. The position and extent of olfactory mucosa was assayed by staining whole mounts (WMs) with neuronal markers. Sections of the OE were analyzed with an extensive group of antibodies directed against cytoskeletal proteins and transcription factors, as were surgical specimens from an esthesioneuroblastoma. Neuron-rich epithelium is always found inferior to the cribriform plate, even at advanced age, despite the interruptions in the neuroepithelial sheet caused by patchy respiratory metaplasia. The pattern of immunostaining with our antibody panel identifies two distinct types of basal cell progenitors in human OE similar to rodents. The panel also clarifies the complex composition of esthesioneuroblastoma. The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurologic disease. The similarities in human versus rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  14. Proteomic Analysis of the Human Olfactory Bulb.

    Science.gov (United States)

    Dammalli, Manjunath; Dey, Gourav; Madugundu, Anil K; Kumar, Manish; Rodrigues, Benvil; Gowda, Harsha; Siddaiah, Bychapur Gowrishankar; Mahadevan, Anita; Shankar, Susarla Krishna; Prasad, Thottethodi Subrahmanya Keshava

    2017-08-01

    The importance of olfaction to human health and disease is often underappreciated. Olfactory dysfunction has been reported in association with a host of common complex diseases, including neurological diseases such as Alzheimer's disease and Parkinson's disease. For health, olfaction or the sense of smell is also important for most mammals, for optimal engagement with their environment. Indeed, animals have developed sophisticated olfactory systems to detect and interpret the rich information presented to them to assist in day-to-day activities such as locating food sources, differentiating food from poisons, identifying mates, promoting reproduction, avoiding predators, and averting death. In this context, the olfactory bulb is a vital component of the olfactory system receiving sensory information from the axons of the olfactory receptor neurons located in the nasal cavity and the first place that processes the olfactory information. We report in this study original observations on the human olfactory bulb proteome in healthy subjects, using a high-resolution mass spectrometry-based proteomic approach. We identified 7750 nonredundant proteins from human olfactory bulbs. Bioinformatics analysis of these proteins showed their involvement in biological processes associated with signal transduction, metabolism, transport, and olfaction. These new observations provide a crucial baseline molecular profile of the human olfactory bulb proteome, and should assist the future discovery of biomarker proteins and novel diagnostics associated with diseases characterized by olfactory dysfunction.

  15. Olfactory dysfunction, olfactory bulb pathology and urban air pollution

    Science.gov (United States)

    Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Osnaya, Norma; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Herritt, Lou; Brooks, Diane; Keefe, Sheyla; Palacios-Moreno, Juan; Villarreal-Calderon, Rodolfo; Torres-Jardón, Ricardo; Medina-Cortina, Humberto; Delgado-Chávez, Ricardo; Aiello-Mora, Mario; Maronpot, Robert R.; Doty, Richard L

    2010-01-01

    Mexico City (MC) residents are exposed to severe air pollution and exhibit olfactory bulb inflammation. We compared the olfactory function of individuals living under conditions of extreme air pollution to that of controls from a relatively clean environment and explore associations between olfaction scores, apolipoprotein E (APOE) status, and pollution exposure. The olfactory bulbs (OBs) of 35 MC and 9 controls 20.8 ± 8.5 y were assessed by light and electron microscopy. The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 62 MC / 25 controls 21.2 ±2.7 y. MC subjects had significantly lower UPSIT scores: 34.24 ± 0.42 versus controls 35.76 ± 0.40, p=0.03. Olfaction deficits were present in 35.5% MC and 12% of controls. MC APOE ε 4 carriers failed 2.4 ± 0.54 items in the 10-item smell identification scale from the UPSIT related to Alzheimer's disease, while APOE 2/3 and 3/3 subjects failed 1.36 ± 0.16 items, p = 0.01. MC residents exhibited OB endothelial hyperplasia, neuronal accumulation of particles (2/35), and immunoreactivity to beta amyloid βA42 (29/35) and/or α-synuclein (4/35) in neurons, glial cells and/or blood vessels. Ultrafine particles were present in OBs endothelial cytoplasm and basement membranes. Control OBs were unremarkable. Air pollution exposure is associated with olfactory dysfunction and OB pathology, APOE 4 may confer greater susceptibility to such abnormalities, and ultrafine particles could play a key role in the OB pathology. This study contributes to our understanding of the influences of air pollution on olfaction and its potential contribution to neurodegeneration. PMID:19297138

  16. Profiling of olfactory receptor gene expression in whole human olfactory mucosa.

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    Christophe Verbeurgt

    Full Text Available Olfactory perception is mediated by a large array of olfactory receptor genes. The human genome contains 851 olfactory receptor gene loci. More than 50% of the loci are annotated as nonfunctional due to frame-disrupting mutations. Furthermore haplotypic missense alleles can be nonfunctional resulting from substitution of key amino acids governing protein folding or interactions with signal transduction components. Beyond their role in odor recognition, functional olfactory receptors are also required for a proper targeting of olfactory neuron axons to their corresponding glomeruli in the olfactory bulb. Therefore, we anticipate that profiling of olfactory receptor gene expression in whole human olfactory mucosa and analysis in the human population of their expression should provide an opportunity to select the frequently expressed and potentially functional olfactory receptors in view of a systematic deorphanization. To address this issue, we designed a TaqMan Low Density Array (Applied Biosystems, containing probes for 356 predicted human olfactory receptor loci to investigate their expression in whole human olfactory mucosa tissues from 26 individuals (13 women, 13 men; aged from 39 to 81 years, with an average of 67±11 years for women and 63±12 years for men. Total RNA isolation, DNase treatment, RNA integrity evaluation and reverse transcription were performed for these 26 samples. Then 384 targeted genes (including endogenous control genes and reference genes specifically expressed in olfactory epithelium for normalization purpose were analyzed using the same real-time reverse transcription PCR platform. On average, the expression of 273 human olfactory receptor genes was observed in the 26 selected whole human olfactory mucosa analyzed, of which 90 were expressed in all 26 individuals. Most of the olfactory receptors deorphanized to date on the basis of sensitivity to known odorant molecules, which are described in the literature, were

  17. Olfactory dysfunction in Iranian diabetic patients.

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    Jalal Mehdizadeh Seraj

    2015-04-01

    Full Text Available Olfactory dysfunction is a known complication of diabetes and, despite its importance in the quality of life, is usually neglected due to its gradual progression. In this study, we aim to determine the prevalence and severity of olfactory dysfunction in diabetics and its association with microangiopathic complications of the disease (neuropathy, nephropathy, and retinopathy. Excluding the confounding factors, a case-control study of 60 eligible subjects, divided into a group of 30 diabetic patients and a group of 30 control subjects was performed. We used "absorbent perfumer's paper strips" method to test the olfactory threshold. In our study, 60% of diabetics were found to have some degree of olfactory dysfunction and a significant difference (P<0.01 between the olfactory threshold of the case and control groups was observed. There were no significant associations between the olfactory dysfunction and age, sex, treatment duration and microangiopathic complications.

  18. Independent control of gamma and theta activity by distinct interneuron networks in the olfactory bulb.

    Science.gov (United States)

    Fukunaga, Izumi; Herb, Jan T; Kollo, Mihaly; Boyden, Edward S; Schaefer, Andreas T

    2014-09-01

    Circuits in the brain possess the ability to orchestrate activities on different timescales, but the manner in which distinct circuits interact to sculpt diverse rhythms remains unresolved. The olfactory bulb is a classic example of a place in which slow theta and fast gamma rhythms coexist. Furthermore, inhibitory interneurons that are generally implicated in rhythm generation are segregated into distinct layers, neatly separating local and global motifs. We combined intracellular recordings in vivo with circuit-specific optogenetic interference to examine the contribution of inhibition to rhythmic activity in the mouse olfactory bulb. We found that the two inhibitory circuits controlled rhythms on distinct timescales: local, glomerular networks coordinated theta activity, regulating baseline and odor-evoked inhibition, whereas granule cells orchestrated gamma synchrony and spike timing. Notably, granule cells did not contribute to baseline rhythms or sniff-coupled odor-evoked inhibition. Thus, activities on theta and gamma timescales are controlled by separate, dissociable inhibitory networks in the olfactory bulb.

  19. Neuronal pattern separation in the olfactory bulb improves odor discrimination learning.

    Science.gov (United States)

    Gschwend, Olivier; Abraham, Nixon M; Lagier, Samuel; Begnaud, Frédéric; Rodriguez, Ivan; Carleton, Alan

    2015-10-01

    Neuronal pattern separation is thought to enable the brain to disambiguate sensory stimuli with overlapping features, thereby extracting valuable information. In the olfactory system, it remains unknown whether pattern separation acts as a driving force for sensory discrimination and the learning thereof. We found that overlapping odor-evoked input patterns to the mouse olfactory bulb (OB) were dynamically reformatted in the network on the timescale of a single breath, giving rise to separated patterns of activity in an ensemble of output neurons, mitral/tufted (M/T) cells. Notably, the extent of pattern separation in M/T assemblies predicted behavioral discrimination performance during the learning phase. Furthermore, exciting or inhibiting GABAergic OB interneurons, using optogenetics or pharmacogenetics, altered pattern separation and thereby odor discrimination learning in a bidirectional way. In conclusion, we propose that the OB network can act as a pattern separator facilitating olfactory stimulus distinction, a process that is sculpted by synaptic inhibition.

  20. Transcriptomic effects of depleted uranium on acetylcholine and cholesterol metabolisms in Alzheimer's disease model; Effets transcriptomiques de l'uranium appauvri sur les metabolismes de l'acetylcholine et du cholesterol chez un modele de maladie d'Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Lestaevel, Ph.; Bensoussan, H.; Racine, R.; Airault, F.; Gourmelon, P.; Souidi, M. [Direction de la radioprotection de l' Homme, service de radiobiologie et d' epidemiologie, laboratoire de radiotoxicologie experimentale, institut de radioprotection et de surete nucleaire, BP no 17, 92262 Fontenay-aux-Roses cedex (France)

    2011-02-15

    Some heavy metals, or aluminium, could participate in the development of Alzheimer disease (AD). Depleted uranium (DU), another heavy metal, modulates the cholinergic system and the cholesterol metabolism in the brain of rats, but without neurological disorders. The aim of this study was to determine what happens in organisms exposed to DU that will/are developing the AD. This study was thus performed on a transgenic mouse model for human amyloid precursor protein (APP), the Tg2576 strain. The possible effects of DU through drinking water (20 mg/L) over an 8-month period were analyzed on acetylcholine and cholesterol metabolisms at gene level in the cerebral cortex. The mRNA levels of choline acetyl transferase (ChAT) vesicular acetylcholine transporter (VAChT) and ATP-binding cassette transporter A1 (ABC A1) decreased in control Tg2576 mice in comparison with wild-type mice (respectively -89%, -86% and -44%, p < 0.05). Chronic exposure of Tg2576 mice to DU increased mRNA levels of ChAT (+189%, p < 0.05), VAChT (+120%, p < 0.05) and ABC A1 (+52%, p < 0.05) compared to control Tg2576 mice. Overall, these modifications of acetylcholine and cholesterol metabolisms did not lead to increased disturbances that are specific of AD, suggesting that chronic DU exposure did not worsen the pathology in this experimental model. (authors)

  1. Role of Centrifugal Projections to the Olfactory Bulb in Olfactory Processing

    Science.gov (United States)

    Kiselycznyk, Carly L.; Zhang, Steven; Linster, Christine

    2006-01-01

    While there is evidence that feedback projections from cortical and neuromodulatory structures to the olfactory bulb are crucial for maintaining the oscillatory dynamics of olfactory bulb processing, it is not clear how changes in dynamics are related to odor perception. Using electrical lesions of the olfactory peduncle, sparing output from the…

  2. SLEEP AND OLFACTORY CORTICAL PLASTICITY

    Directory of Open Access Journals (Sweden)

    Dylan eBarnes

    2014-04-01

    Full Text Available In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders.

  3. Fetal alcohol exposure leads to abnormal olfactory bulb development and impaired odor discrimination in adult mice

    Directory of Open Access Journals (Sweden)

    Akers Katherine G

    2011-07-01

    Full Text Available Abstract Background Children whose mothers consumed alcohol during pregnancy exhibit widespread brain abnormalities and a complex array of behavioral disturbances. Here, we used a mouse model of fetal alcohol exposure to investigate relationships between brain abnormalities and specific behavioral alterations during adulthood. Results Mice drank a 10% ethanol solution throughout pregnancy. When fetal alcohol-exposed offspring reached adulthood, we used high resolution MRI to conduct a brain-wide screen for structural changes and found that the largest reduction in volume occurred in the olfactory bulbs. Next, we tested adult mice in an associative olfactory task and found that fetal alcohol exposure impaired discrimination between similar odors but left odor memory intact. Finally, we investigated olfactory bulb neurogenesis as a potential mechanism by performing an in vitro neurosphere assay, in vivo labeling of new cells using BrdU, and in vivo labeling of new cells using a transgenic reporter system. We found that fetal alcohol exposure decreased the number of neural precursor cells in the subependymal zone and the number of new cells in the olfactory bulbs during the first few postnatal weeks. Conclusions Using a combination of techniques, including structural brain imaging, in vitro and in vivo cell detection methods, and behavioral testing, we found that fetal alcohol exposure results in smaller olfactory bulbs and impairments in odor discrimination that persist into adulthood. Furthermore, we found that these abnormalities in olfactory bulb structure and function may arise from deficits in the generation of new olfactory bulb neurons during early postnatal development.

  4. 5HTR3A-driven GFP labels immature olfactory sensory neurons.

    Science.gov (United States)

    Finger, Thomas E; Bartel, Dianna L; Shultz, Nicole; Goodson, Noah B; Greer, Charles A

    2017-05-01

    The ionotropic serotonin receptor, 5-HT3 , is expressed by many developing neurons within the central nervous system. Since the olfactory epithelium continues to generate new olfactory sensory neurons (OSNs) throughout life, we investigated the possibility that 5-HT3 is expressed in the adult epithelium. Using a transgenic mouse in which the promoter for the 5-HT3a subunit drives expression of green fluorescent protein (GFP), we assessed the expression of this marker in the olfactory epithelium of adult mice. Both the native 5-HT3a mRNA and GFP are expressed within globose basal cells of the olfactory and vomeronasal epithelium in adult mice. Whereas the 5-HT3a mRNA disappears relatively quickly after final cell division, the GFP label persists for about 5 days, thereby labeling immature OSNs in both the main olfactory system and vomeronasal organ. The GFP-labeled cells include both proliferative globose basal cells as well as immature OSNs exhibiting the hallmarks of ongoing differentiation including GAP43, PGP9.5, but the absence of olfactory marker protein. Some of the GFP-labeled OSNs show characteristics of more mature yet still developing OSNs including the presence of cilia extending from the apical knob and expression of NaV1.5, a component of the transduction cascade. These findings suggest that 5-HT3a is indicative of a proliferative or developmental state, regardless of age, and that the 5-HT3A GFP mice may prove useful for future studies of neurogenesis in the olfactory epithelium. J. Comp. Neurol. 525:1743-1755, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Cilia- and Flagella-Associated Protein 69 Regulates Olfactory Transduction Kinetics in Mice.

    Science.gov (United States)

    Talaga, Anna K; Dong, Frederick N; Reisert, Johannes; Zhao, Haiqing

    2017-06-07

    Animals detect odorous chemicals through specialized olfactory sensory neurons (OSNs) that transduce odorants into neural electrical signals. We identified a novel and evolutionarily conserved protein, cilia- and flagella-associated protein 69 (CFAP69), in mice that regulates olfactory transduction kinetics. In the olfactory epithelium, CFAP69 is enriched in OSN cilia, where olfactory transduction occurs. Bioinformatic analysis suggests that a large portion of CFAP69 can form Armadillo-type α-helical repeats, which may mediate protein-protein interactions. OSNs lacking CFAP69, remarkably, displayed faster kinetics in both the on and off phases of electrophysiological responses at both the neuronal ensemble level as observed by electroolfactogram and the single-cell level as observed by single-cell suction pipette recordings. In single-cell analysis, OSNs lacking CFAP69 showed faster response integration and were able to fire APs more faithfully to repeated odor stimuli. Furthermore, both male and female mutant mice that specifically lack CFAP69 in OSNs exhibited attenuated performance in a buried food pellet test when a background of the same odor to the food pellet was present even though they should have better temporal resolution of coding olfactory stimulation at the peripheral. Therefore, the role of CFAP69 in the olfactory system seems to be to allow the olfactory transduction machinery to work at a precisely regulated range of response kinetics for robust olfactory behavior.SIGNIFICANCE STATEMENT Sensory receptor cells are generally thought to evolve to respond to sensory cues as fast as they can. This idea is consistent with mutational analyses in various sensory systems, where mutations of sensory receptor cells often resulted in reduced response size and slowed response kinetics. Contrary to this idea, we have found that there is a kinetic "damper" present in the olfactory transduction cascade of the mouse that slows down the response kinetics and, by

  6. TSHZ1-dependent gene regulation is essential for olfactory bulb development and olfaction.

    Science.gov (United States)

    Ragancokova, Daniela; Rocca, Elena; Oonk, Anne M M; Schulz, Herbert; Rohde, Elvira; Bednarsch, Jan; Feenstra, Ilse; Pennings, Ronald J E; Wende, Hagen; Garratt, Alistair N

    2014-03-01

    The olfactory bulb (OB) receives odor information from the olfactory epithelium and relays this to the olfactory cortex. Using a mouse model, we found that development and maturation of OB interneurons depends on the zinc finger homeodomain factor teashirt zinc finger family member 1 (TSHZ1). In mice lacking TSHZ1, neuroblasts exhibited a normal tangential migration to the OB; however, upon arrival to the OB, the neuroblasts were distributed aberrantly within the radial dimension, and many immature neuroblasts failed to exit the rostral migratory stream. Conditional deletion of Tshz1 in mice resulted in OB hypoplasia and severe olfactory deficits. We therefore investigated olfaction in human subjects from families with congenital aural atresia that were heterozygous for TSHZ1 loss-of-function mutations. These individuals displayed hyposmia, which is characterized by impaired odor discrimination and reduced olfactory sensitivity. Microarray analysis, in situ hybridization, and ChIP revealed that TSHZ1 bound to and regulated expression of the gene encoding prokineticin receptor 2 (PROKR2), a G protein–coupled receptor essential for OB development. Mutations in PROKR2 lead to Kallmann syndrome, characterized by anosmia and hypogonadotrophic hypogonadism. Our data indicate that TSHZ1 is a key regulator of mammalian OB development and function and controls the expression of molecules involved in human Kallmann syndrome.

  7. Persistent, generalized hypersensitivity of olfactory bulb interneurons after olfactory fear generalization.

    Science.gov (United States)

    Kass, Marley D; McGann, John P

    2017-11-08

    Generalization of fear from previously threatening stimuli to novel but related stimuli can be beneficial, but if fear overgeneralizes to inappropriate situations it can produce maladaptive behaviors and contribute to pathological anxiety. Appropriate fear learning can selectively facilitate early sensory processing of threat-predictive stimuli, but it is unknown if fear generalization has similarly generalized neurosensory consequences. We performed in vivo optical neurophysiology to visualize odor-evoked neural activity in populations of periglomerular interneurons in the olfactory bulb 1 day before, 1 day after, and 1 month after each mouse underwent an olfactory fear conditioning paradigm designed to promote generalized fear of odors. Behavioral and neurophysiological changes were assessed in response to a panel of odors that varied in similarity to the threat-predictive odor at each time point. After conditioning, all odors evoked similar levels of freezing behavior, regardless of similarity to the threat-predictive odor. Freezing significantly correlated with large changes in odor-evoked periglomerular cell activity, including a robust, generalized facilitation of the response to all odors, broadened odor tuning, and increased neural responses to lower odor concentrations. These generalized effects occurred within 24 h of a single conditioning session, persisted for at least 1 month, and were detectable even in the first moments of the brain's response to odors. The finding that generalized fear includes altered early sensory processing of not only the threat-predictive stimulus but also novel though categorically-similar stimuli may have important implications for the etiology and treatment of anxiety disorders with sensory sequelae. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Induction of associative olfactory memory by targeted activation of single olfactory neurons in Drosophila larvae.

    Science.gov (United States)

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-04-25

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by ChR2-mediated optical activation of a specific class of olfactory neurons. We show that targeted activation of the olfactory receptor and the octopaminergic neurons is indeed sufficient for the formation of associative olfactory memory in the larval brain. We also show that targeted stimulation of only a single type of olfactory receptor neurons is sufficient to induce olfactory memory that is indistinguishable from natural memory induced by the activation of multiple olfactory receptor neurons.

  9. Olfactory regulation of mosquito-host interactions

    NARCIS (Netherlands)

    Zwiebel, L.J.; Takken, W.

    2004-01-01

    Mosquitoes that act as disease vectors rely upon olfactory cues to direct several important behaviors that are fundamentally involved in establishing their overall vectorial capacity. Of these, the propensity to select humans for blood feeding is arguably the most important of these olfactory driven

  10. Sensory-Evoked Intrinsic Imaging Signals in the Olfactory Bulb Are Independent of Neurovascular Coupling

    Directory of Open Access Journals (Sweden)

    Roberto Vincis

    2015-07-01

    Full Text Available Functional brain-imaging techniques used in humans and animals, such as functional MRI and intrinsic optical signal (IOS imaging, are thought to largely rely on neurovascular coupling and hemodynamic responses. Here, taking advantage of the well-described micro-architecture of the mouse olfactory bulb, we dissected the nature of odor-evoked IOSs. Using in vivo pharmacology in transgenic mouse lines reporting activity in different cell types, we show that parenchymal IOSs are largely independent of neurotransmitter release and neurovascular coupling. Furthermore, our results suggest that odor-evoked parenchymal IOSs originate from changes in light scattering of olfactory sensory neuron axons, mostly due to water movement following action potential propagation. Our study sheds light on a direct correlate of neuronal activity, which may be used for large-scale functional brain imaging.

  11. Duration and specificity of olfactory nonassociative memory.

    Science.gov (United States)

    Freedman, Kaitlin G; Radhakrishna, Sreya; Escanilla, Olga; Linster, Christiane

    2013-05-01

    Olfactory habituation is a simple form of nonassociative memory in which responsiveness to stable but behaviorally nonsignificant stimuli is decreased. Olfactory habituation has recently become a paradigm widely used to probe the neural substrate underlying olfactory perception and memory. This simple behavioral paradigm has been used successfully used to probe many aspects of olfactory processing, and it has recently become clear that the neural processes underlying olfactory habituation can depend on the task parameters used. We here further investigate memory specificity and duration using 2 variations in task parameters: the number of habituation trials and the time delay between habituation and cross-habituation testing. We find that memory specificity increases with the number of habituation trials but decreases with time after the last habituation trial.

  12. Olfactory neuroblastoma in a horse.

    Science.gov (United States)

    Yamate, Jyoji; Izawa, Takeshi; Ogata, Keiko; Kobayashi, Osamu; Okajima, Ryoko; Kuwamura, Mitsuru; Kotani, Takao; Aoki, Mika

    2006-05-01

    An 11-year-old thoroughbred gelding was euthanatized because of right nasal cavity tumor. The tumor consisted of round to oval cells with a scanty cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes, as well as microcysts were seen. Neoplastic cells were immunoreactive to vimentin, S-100 protein, and neuron-specific enolase, glial fibrillary acidic protein and microtube-associated protein in varying degrees, indicating neurogenic nature. Based on these findings, this tumor was diagnosed as an olfactory neuroblastoma. Since this type is an uncommon tumor showing histological variety, the nature is discussed.

  13. Olfactory Dysfunction in Nasal Bone Fracture.

    Science.gov (United States)

    Kim, Sug Won; Park, Beom; Lee, Tae Geun; Kim, Ji Ye

    2017-06-01

    All nasal bone fractures have the potential for worsening of olfactory function. However, few studies have studied the olfactory outcomes following reduction of nasal bone fractures. This study evaluates posttraumatic olfactory dysfunction in patients with nasal bone fracture before and after closed reduction. A prospective study was conducted for all patients presenting with nasal bone fracture (n=97). Each patient consenting to the study underwent the Korean version of Sniffin' Sticks test (KVSS II) before operation and at 6 month after closed reduction. The nasal fractures were divided according to the nasal bone fracture classification by Haug and Prather (Types I-IV). The olfactory scores were compared across fracture types and between preoperative and postoperative settings. Olfactory dysfunction was frequent after nasal fracture (45/97, 46.4%). Our olfactory assessment using the KVSS II test revealed that fracture reduction was not associated with improvements in the mean test score in Type I or Type II fractures. More specifically, the mean posttraumatic Threshold, discrimination and identification score decreased from 28.8 points prior to operation to 23.1 point at 6 months for Type II fracture with septal fracture. Our study has revealed two alarming trends regarding post-nasal fracture olfactory dysfunction. First, our study demonstrated that almost half (46.4%) of nasal fracture patients experience posttraumatic olfactory dysfunction. Second, closed reduction of these fractures does not lead to improvements olfaction at 6 months, which suggest that olfactory dysfunction is probably due to factors other than the fracture itself. The association should be further explored between injuries that lead to nasal fracture and the mechanism behind posttraumatic olfactory dysfunction.

  14. NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps.

    Science.gov (United States)

    Gussing, Fredrik; Bohm, Staffan

    2004-05-01

    The mouse olfactory epithelium (OE) is divided into spatial zones, each containing neurons expressing zone-specific subsets of odorant receptor genes. Likewise, the vomeronasal (VN) organ is organized into apical and basal subpopulations of neurons expressing different VN receptor gene families. Axons projecting from the different OE zones and VN subpopulations form synapses within circumscribed regions in the glomerular layer of the olfactory bulb (OB) and accessory olfactory bulb (AOB), respectively. We here show that mature neurons in one defined zone selectively express NADPH:quinone oxidoreductase (NQO1), an enzyme that catalyses reduction of quinones. Immunohistochemistry and in situ hybridization analyses show non-overlapping expression of NQO1 and the Rb8 neural cell adhesion molecule (RNCAM/OCAM) in OE and axon terminals within glomeruli of the OB. In addition, NQO1 immunoreactivity reveals selective, zone-specific axon fasciculation in the olfactory nerve. VN subpopulations do not show complementary patterns of RNCAM and NQO1 immunoreactivity, instead both genes are co-expressed in apical VN neurons that project to the rostral AOB. These results indicate that one division of both the accessory and the main olfactory projection maps are composed of sensory neurons that are specialized to reduce environmental and/or endogenously produced quinones via an NQO1-dependent mechanism. The role of NQO1 in bioactivation of quinoidal drugs also points to a connection between zone-specific NQO1 expression and zone-specific toxicity of certain olfactory toxins.

  15. Expression of connexin 57 in the olfactory epithelium and olfactory bulb.

    Science.gov (United States)

    Zhang, Chunbo

    2011-11-01

    In the visual system, deletion of connexin 57 (Cx57) reduces gap junction coupling among horizontal cells and results in smaller receptive fields. To explore potential functions of Cx57 in olfaction, in situ hybridization and immunohistochemistry methods were used to investigate expression of Cx57 in the olfactory epithelium and olfactory bulb. Hybridization signal was stronger in the olfactory epithelial layer compared to the connective tissue underneath. Within the sensory epithelial layer, hybridization signal was visible in sublayers containing cell bodies of basal cells and olfactory neurons but not evident at the apical sublayer comprising cell bodies of sustentacular cells. These Cx57 positive cells were clustered into small groups to form different patterns in the olfactory epithelium. However, individual patterns did not associate with specific regions of olfactory turbinates or specific olfactory receptor zones. Patched distribution of hybridization positive cells was also observed in the olfactory bulb and accessory olfactory bulb in layers where granule cells, mitral cells, and juxtaglomerular cells reside. Immunostaining was observed in the cell types described above but the intensity was weaker than that in the retina. This study has provided anatomical basis for future studies on the function of Cx57 in the olfactory system. Copyright © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  16. Smelly primes - when olfactory primes do or do not work

    NARCIS (Netherlands)

    Smeets, M. A M|info:eu-repo/dai/nl/141926600; Dijksterhuis, G. B.

    2014-01-01

    In applied olfactory cognition the effects that olfactory stimulation can have on (human) behavior are investigated. To enable an efficient application of olfactory stimuli a model of how they may lead to a change in behavior is proposed. To this end we use the concept of olfactory priming.

  17. Single Ca(2+)-activated Cl(-) channel currents recorded from toad olfactory cilia.

    Science.gov (United States)

    Delgado, Ricardo; Mura, Casilda V; Bacigalupo, Juan

    2016-04-25

    Odor transduction, occurring in the chemosensory cilia of vertebrate olfactory sensory neurons, is triggered by guanosine triphosphate-coupled odor receptors and mediated by a cyclic adenosine monophosphate (cAMP) signaling cascade, where cAMP opens cationic non-selective cyclic nucleotide-gated (CNG) channels. Calcium enters through CNG gates Ca(2+)-activated Cl(-) channels, allowing a Cl(-) inward current that enhances the depolarization initiated by the CNG-dependent inward current. The anoctamin channel 2, ANO2, is considered the main Ca(2+)-activated Cl(-) channel of olfactory transduction. Although Ca(2+)-activated Cl(-) channel-dependent currents in olfactory sensory neurons were reported to be suppressed in ANO2-knockout mice, field potentials from their olfactory epithelium were only modestly diminished and their smell-dependent behavior was unaffected, suggesting the participation of additional Ca(2+)-activated Cl(-) channel types. The Bestrophin channel 2, Best2, was also detected in mouse olfactory cilia and ClCa4l, belonging to the ClCa family of Ca(2+)-activated Cl(-) channels, were found in rat cilia. Best2 knock-out mice present no electrophysiological or behavioral impairment, while the ClCa channels have not been functionally studied; therefore, the overall participation of all these channels in olfactory transduction remains unresolved. We explored the presence of detectable Ca(2+)-activated Cl(-) channels in toad olfactory cilia by recording from inside-out membrane patches excised from individual cilia and detected unitary Cl(-) current events with a pronounced Ca(2+) dependence, corresponding to 12 and 24 pS conductances, over tenfold higher than the aforementioned channels, and a approx. fivefold higher Ca(2+) affinity (K0.5 = 0.38 µM). Remarkably, we observed immunoreactivity to anti-ClCa and anti-ANO2 antibodies in the olfactory cilia, suggesting a possible cooperative function of both channel type in chemotransduction. These results

  18. Preliminary Modeling and Simulation Study on Olfactory Cell Sensation

    Science.gov (United States)

    Zhou, Jun; Yang, Wei; Chen, Peihua; Liu, Qingjun; Wang, Ping

    2009-05-01

    This paper introduced olfactory sensory neuron's whole-cell model with a concrete voltage-gated ionic channels and simulation. Though there are many models in olfactory sensory neuron and olfactory bulb, it remains uncertain how they express the logic of olfactory information processing. In this article, the olfactory neural network model is also introduced. This model specifies the connections among neural ensembles of the olfactory system. The simulation results of the neural network model are consistent with the observed olfactory biological characteristics such as 1/f-type power spectrum and oscillations.

  19. [Odor sensing system and olfactory display].

    Science.gov (United States)

    Nakamoto, Takamichi

    2014-01-01

    In this review, an odor sensing system and an olfactory display are introduced into people in pharmacy. An odor sensing system consists of an array of sensors with partially overlapping specificities and pattern recognition technique. One of examples of odor sensing systems is a halitosis sensor which quantifies the mixture composition of three volatile sulfide compounds. A halitosis sensor was realized using a preconcentrator to raise sensitivity and an electrochemical sensor array to suppress the influence of humidity. Partial least squares (PLS) method was used to quantify the mixture composition. The experiment reveals that the sufficient accuracy was obtained. Moreover, the olfactory display, which present scents to human noses, is explained. A multi-component olfactory display enables the presentation of a variety of smells. The two types of multi-component olfactory display are described. The first one uses many solenoid valves with high speed switching. The valve ON frequency determines the concentration of the corresponding odor component. The latter one consists of miniaturized liquid pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable olfactory display without smell persistence. Finally, the application of the olfactory display is demonstrated. Virtual ice cream shop with scents was made as a content of interactive art. People can enjoy harmony among vision, audition and olfaction. In conclusion, both odor sensing system and olfactory display can contribute to the field of human health care.

  20. Olfactory bulb as an alternative in neurotransplantation

    Directory of Open Access Journals (Sweden)

    Руслан Романович Новиков

    2015-05-01

    Full Text Available The article examines the ethical and legal aspects of transplantation of embryonic neural tissue, structure of the rat olfactory bulb. It is given substantiation for its use as a possible alternative version of the embryonic neural tissue at damage in the cerebral hemispheres in the experiment.Materials and methods. Detailed description of the fault model of the cerebral hemispheres of the brain of rats, olfactory bulb biopsy procedure, cultivation of olfactory bulb suspension and fetal neural tissue, comparison of the functional aspects of transplantation of the olfactory bulb and the embryonic neural tissue.Results. The obtained data are similar to structure of olfactory bulb and fetal tissues during culturing. Recovery in the motor areas varies by the time factor and less intense in the group of the olfactory bulb and the group without tissue transplantation.Conclusions. Comparative analysis of the effectiveness of transplantation of embryonic neural tissue and olfactory bulb in the injured brain allows us to speak about the positive results of these groups to the difference in the duration of the recovery process

  1. Imaging the olfactory tract (Cranial Nerve no.1)

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    Duprez, Thierry P. [Department of Radiology and Medical Imaging, Universite catholique de Louvain, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200-Brussels (Belgium)], E-mail: Thierry.Duprez@uclouvain.be; Rombaux, Philippe [Department of Otorhinolaryngology, Universite catholique de Louvain, Cliniques Universitaires Saint-Luc, Avenue Hippocrate, 10, 1200-Brussels (Belgium)], E-mail: Philippe.Rombaux@uclouvain.be

    2010-05-15

    This review paper browses pros and cons of the different radiological modalities for imaging the olfactory tract and highlights the potential benefits and limitation of more recent advances in MR and CT technology. A systematic pictorial overview of pathological conditions affecting olfactory sense is given. Techniques for collecting quantitative data on olfactory bulb volume and on olfactory sulcus depth are described. At last, insights into functional imaging of olfactory sense are shown.

  2. Neuronal organization of olfactory bulb circuits

    Science.gov (United States)

    Nagayama, Shin; Homma, Ryota; Imamura, Fumiaki

    2014-01-01

    Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit. PMID:25232305

  3. Neuronal organization of olfactory bulb circuits

    Directory of Open Access Journals (Sweden)

    Shin eNagayama

    2014-09-01

    Full Text Available Olfactory sensory neurons extend their axons solely to the olfactory bulb, which is dedicated to odor information processing. The olfactory bulb is divided into multiple layers, with different types of neurons found in each of the layers. Therefore, neurons in the olfactory bulb have conventionally been categorized based on the layers in which their cell bodies are found; namely, juxtaglomerular cells in the glomerular layer, tufted cells in the external plexiform layer, mitral cells in the mitral cell layer, and granule cells in the granule cell layer. More recently, numerous studies have revealed the heterogeneous nature of each of these cell types, allowing them to be further divided into subclasses based on differences in morphological, molecular, and electrophysiological properties. In addition, technical developments and advances have resulted in an increasing number of studies regarding cell types other than the conventionally categorized ones described above, including short-axon cells and adult-generated interneurons. Thus, the expanding diversity of cells in the olfactory bulb is now being acknowledged. However, our current understanding of olfactory bulb neuronal circuits is mostly based on the conventional and simplest classification of cell types. Few studies have taken neuronal diversity into account for understanding the function of the neuronal circuits in this region of the brain. This oversight may contribute to the roadblocks in developing more precise and accurate models of olfactory neuronal networks. The purpose of this review is therefore to discuss the expanse of existing work on neuronal diversity in the olfactory bulb up to this point, so as to provide an overall picture of the olfactory bulb circuit.

  4. [Olfactory bulb volume and depth of olfactory sulcus in patients with allergic rhinitis].

    Science.gov (United States)

    Zhang, Qiang; Liu, Gang; Hang, Wei

    2014-12-01

    To explore the olfactory abilities in patients with allergic rhinitis (AR), analyze the correlation between olfactory bulb (OB) volume with depth of olfactory sulcus (OS) and olfactory function in patients with AR. One hundred patients with AR were compared with one hundred controls in terms of olfactory function T&T testing, OB volume and depth of OS assessed with magnetic resonance imaging (MRI). T&T testing and MRI were done after a year in 100 AR patients,the results were compared with the initial results. The OB volume in AR patients was (29.53±3.95) mm3 on the left, (29.67±14.21)mm3 on the right, (29.61±4.05) mm3 on average; The OB volume in controls was (48.93±6.73)mm3 on the left side, (48.81±7.43)mm3 on the right side, (48.85±7.11)mm3 on average; The OB volume in AR patients was less then the control group(t= 6.321, 6.141, 6.221, P0.05). Olfactory discriminate threshold was negatively correlated with OB volume in AR patients (r=-0.46, P0.05). Among 100 followed-up AR patients, 43 showed increased in OB volume and olfactory function after a year, but there was no statistical difference (t= 0. 811,0. 843, 0.826, P>0.05; Z=1.911, P>0.05) ,and the other 57 showed no significant changes of OB volume and olfactory function. In AR patients, the OB volume and olfactory function decreased, but the depth of OS had no significant changes. The OB volume is correlated with olfactory function, while the depth of OS is no correlated with olfactory function. Conservative treatment had some clinical significance on the recovery of olfactory function in patients with AR.

  5. Repeated formaldehyde inhalation impaired olfactory function and changed SNAP25 proteins in olfactory bulb.

    Science.gov (United States)

    Zhang, Qi; Yan, Weiqun; Bai, Yang; Zhu, Yingqiao; Ma, Jie

    2014-10-01

    Formaldehyde inhalation exposure, which can occur through occupational exposure, can lead to sensory irritation, neurotoxicity, mood disorders, and learning and memory impairment. However, its influence on olfactory function is unclear. To investigate the mechanism and the effect of repeated formaldehyde inhalation exposure on olfactory function. Rats were treated with formaldehyde inhalation (13·5±1·5 ppm, twice 30 minutes/day) for 14 days. Buried food pellet and locomotive activity tests were used to detect olfactory function and locomotion. Western blots were used to evaluate synaptosomal-associated protein 25 (SNAP25) protein levels in the olfactory bulb (OB) lysate and synaptosome, as well as mature and immature olfactory sensory neuron markers, olfactory marker protein (OMP), and Tuj-1. Real-time polymerase chain reaction (PCR) was used to detect SNAP25 mRNA amounts. Repeated formaldehyde inhalation exposure impaired olfactory function, whereas locomotive activities were unaffected. SNAP25 protein decreased significantly in the OB, but not in the occipital lobe. SNAP25 also decreased in the OB synaptosome when synaptophysin did not change after formaldehyde treatment. mRNA levels of SNAP25A and SNAP25B were unaffected. Mature and immature olfactory sensory neuron marker, OMP, and Tuj-1, did not change after formaldehyde treatment. Repeated formaldehyde exposure impaired olfactory function by disturbing SNAP25 protein in the OB.

  6. Analysis of olfactory function and the depth of olfactory sulcus in patients with Parkinson's disease.

    Science.gov (United States)

    Kim, Ji Youn; Lee, Won Yong; Chung, Eun Joo; Dhong, Hun-Jong

    2007-08-15

    Olfactory deficit is known to occur frequently in Parkinson's disease (PD). This study aimed to explore olfactory deficit in PD and to investigate its possible correlation with the disease severity or the depth of the olfactory sulcus. Fifty-nine PD patients and 25 normal controls were examined by the odor identification test with the crosscultural smell identification test (CC-SIT). Among these subjects, the depth of the olfactory sulcus of 42 PD patients and 8 controls was measured in the plane of the posterior tangent through the eyeballs using the coronal view brain MRI. The CC-SIT scores of the PD patients were significantly lower than those of the normal control (P0.05). Our study confirms that CC-SIT is a helpful test in detecting the olfactory deficit in Korean PD patients. The absence of correlation of olfactory deficit with the disease severity or the depth of olfactory sulcus may suggest that olfactory loss precede the development of motor signs and not be a primary consequence of damage to the olfactory sulcus. Copyright (c) 2007 Movement Disorder Society.

  7. Update on the olfactory receptor (OR gene superfamily

    Directory of Open Access Journals (Sweden)

    Olender Tsviya

    2008-09-01

    Full Text Available Abstract The olfactory receptor gene (OR superfamily is the largest in the human genome. The superfamily contains 390 putatively functional genes and 465 pseudogenes arranged into 18 gene families and 300 subfamilies. Even members within the same subfamily are often located on different chromosomes. OR genes are located on all autosomes except chromosome 20, plus the X chromosome but not the Y chromosome. The gene:pseudogene ratio is lowest in human, higher in chimpanzee and highest in rat and mouse -- most likely reflecting the greater need of olfaction for survival in the rodent than in the human. The OR genes undergo allelic exclusion, each sensory neurone expressing usually only one odourant receptor allele; the mechanism by which this phenomenon is regulated is not yet understood. The nomenclature system (based on evolutionary divergence of genes into families and subfamilies of the OR gene superfamily has been designed similarly to that originally used for the CYP gene superfamily.

  8. Modeling olfactory bulb evolution through primate phylogeny.

    Science.gov (United States)

    Heritage, Steven

    2014-01-01

    Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution.

  9. Cladistic Analysis of Olfactory and Vomeronasal Systems

    Science.gov (United States)

    Ubeda-Bañon, Isabel; Pro-Sistiaga, Palma; Mohedano-Moriano, Alicia; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Gutierrez-Castellanos, Nicolás; Lanuza, Enrique; Martinez-Garcia, Fernando; Martinez-Marcos, Alino

    2010-01-01

    Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical “cortex.” We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials, and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis), short-tailed opossums (Monodelphis domestica), and rats (Rattus norvegicus) by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines). In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphaericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses. PMID:21290004

  10. System identification of Drosophila olfactory sensory neurons

    OpenAIRE

    Kim, Anmo J.; Lazar, Aurel A.; Slutskiy, Yevgeniy B.

    2010-01-01

    The lack of a deeper understanding of how olfactory sensory neurons (OSNs) encode odors has hindered the progress in understanding the olfactory signal processing in higher brain centers. Here we employ methods of system identification to investigate the encoding of time-varying odor stimuli and their representation for further processing in the spike domain by Drosophila OSNs. In order to apply system identification techniques, we built a novel low-turbulence odor delivery system that allowe...

  11. Olfactory bulb encoding during learning under anaesthesia

    Directory of Open Access Journals (Sweden)

    Alister U Nicol

    2014-06-01

    Full Text Available Neural plasticity changes within the olfactory bulb are important for olfactory learning, although how neural encoding changes support new associations with specific odours and whether they can be investigated under anaesthesia, remain unclear. Using the social transmission of food preference olfactory learning paradigm in mice in conjunction with in vivo microdialysis sampling we have shown firstly that a learned preference for a scented food odour smelled on the breath of a demonstrator animal occurs under isofluorane anaesthesia. Furthermore, subsequent exposure to this cued odour under anaesthesia promotes the same pattern of increased release of glutamate and GABA in the olfactory bulb as previously found in conscious animals following olfactory learning, and evoked GABA release was positively correlated with the amount of scented food eaten. In a second experiment, multiarray (24 electrodes electrophysiological recordings were made from olfactory bulb mitral cells under isofluorane anaesthesia before, during and after a novel scented food odour was paired with carbon disulfide. Results showed significant increases in overall firing frequency to the cued-odour during and after learning and decreases in response to an uncued odour. Analysis of patterns of changes in individual neurons revealed that a substantial proportion (>50% of them significantly changed their response profiles during and after learning with most of those previously inhibited becoming excited. A large number of cells exhibiting no response to the odours prior to learning were either excited or inhibited afterwards. With the uncued odour many previously responsive cells became unresponsive or inhibited. Learning associated changes only occurred in the posterior part of the olfactory bulb. Thus olfactory learning under anaesthesia promotes extensive, but spatially distinct, changes in mitral cell networks to both cued and uncued odours as well as in evoked glutamate and

  12. Cladistic analysis of olfactory and vomeronasal systems

    Directory of Open Access Journals (Sweden)

    Alino eMartinez-Marcos

    2011-01-01

    Full Text Available Most tetrapods possess two nasal organs for detecting chemicals in their environment, which are the sensory detectors of the olfactory and vomeronasal systems. The seventies’ view that the olfactory system was only devoted to sense volatiles, whereas the vomeronasal system was exclusively specialized for pheromone detection was challenged by accumulating data showing deep anatomical and functional interrelationships between both systems. In addition, the assumption that the vomeronasal system appeared as an adaptation to terrestrial life is being questioned as well. The aim of the present work is to use a comparative strategy to gain insight in our understanding of the evolution of chemical cortex. We have analyzed the organization of the olfactory and vomeronasal cortices of reptiles, marsupials and placental mammals and we have compared our findings with data from other taxa in order to better understand the evolutionary history of the nasal sensory systems in vertebrates. The olfactory and vomeronsasal cortices have been re-investigated in garter snakes (Thamnophis sirtalis, short-tailed opossums (Monodelphis domestica and rats (Rattus norvegicus by tracing the efferents of the main and accessory olfactory bulbs using injections of neuroanatomical anterograde tracers (dextran-amines. In snakes, the medial olfactory tract is quite evident, whereas the main vomeronasal-recipient structure, the nucleus sphericus is a folded cortical-like structure, located at the caudal edge of the amygdala. In marsupials, which are acallosal mammals, the rhinal fissure is relatively dorsal and the olfactory and vomeronasal cortices relatively expanded. Placental mammals, like marsupials, show partially overlapping olfactory and vomeronasal projections in the rostral basal telencephalon. These data raise the interesting question of how the telencephalon has been re-organized in different groups according to the biological relevance of chemical senses.

  13. Functional imaging of cortical feedback projections to the olfactory bulb

    Directory of Open Access Journals (Sweden)

    Markus eRothermel

    2014-07-01

    Full Text Available Processing of sensory information is substantially shaped by centrifugal, or feedback, projections from higher cortical areas, yet the functional properties of these projections are poorly characterized. Here, we used genetically-encoded calcium sensors (GCaMPs to functionally image activation of centrifugal projections targeting the olfactory bulb (OB. The OB receives massive centrifugal input from cortical areas but there has been as yet no characterization of their activity in vivo. We focused on projections to the OB from the anterior olfactory nucleus (AON, a major source of cortical feedback to the OB. We expressed GCaMP selectively in AON projection neurons using a mouse line expressing Cre recombinase (Cre in these neurons and Cre-dependent viral vectors injected into AON, allowing us to image GCaMP fluorescence signals from their axon terminals in the OB. Electrical stimulation of AON evoked large fluorescence signals that could be imaged from the dorsal OB surface in vivo. Surprisingly, odorants also evoked large signals that were transient and coupled to odorant inhalation both in the anesthetized and awake mouse, suggesting that feedback from AON to the OB is rapid and robust across different brain states. The strength of AON feedback signals increased during wakefulness, suggesting a state-dependent modulation of cortical feedback to the OB. Two-photon GCaMP imaging revealed that different odorants activated different subsets of centrifugal AON axons and could elicit both excitation and suppression in different axons, indicating a surprising richness in the representation of odor information by cortical feedback to the OB. Finally, we found that activating neuromodulatory centers such as basal forebrain drove AON inputs to the OB independent of odorant stimulation. Our results point to the AON as a multifunctional cortical area that provides ongoing feedback to the OB and also serves as a descending relay for other neuromodulatory

  14. Sendai Virus Induces Persistent Olfactory Dysfunction in a Murine Model of PVOD via Effects on Apoptosis, Cell Proliferation, and Response to Odorants.

    Directory of Open Access Journals (Sweden)

    Jun Tian

    Full Text Available Viral infection is a common cause of olfactory dysfunction. The complexities of studying post-viral olfactory loss in humans have impaired further progress in understanding the underlying mechanism. Recently, evidence from clinical studies has implicated Parainfluenza virus 3 as a causal agent. An animal model of post viral olfactory disorders (PVOD would allow better understanding of disease pathogenesis and represent a major advance in the field.To develop a mouse model of PVOD by evaluating the effects of Sendai virus (SeV, the murine counterpart of Parainfluenza virus, on olfactory function and regenerative ability of the olfactory epithelium.C57BL/6 mice (6-8 months old were inoculated intranasally with SeV or ultraviolet (UV-inactivated virus (UV-SeV. On days 3, 10, 15, 30 and 60 post-infection, olfactory epithelium was harvested and analyzed by histopathology and immunohistochemical detection of S-phase nuclei. We also measured apoptosis by TUNEL assay and viral load by real-time PCR. The buried food test (BFT was used to measure olfactory function of mice at day 60. In parallel, cultured murine olfactory sensory neurons (OSNs infected with SeV or UV-SeV were tested for odorant-mixture response by measuring changes in intracellular calcium concentrations indicated by fura-4 AM assay.Mice infected with SeV suffered from olfactory dysfunction, peaking on day 15, with no loss observed with UV-SeV. At 60 days, four out of 12 mice infected with SeV still had not recovered, with continued normal function in controls. Viral copies of SeV persisted in both the olfactory epithelium (OE and the olfactory bulb (OB for at least 60 days. At day 10 and after, both unit length labeling index (ULLI of apoptosis and ULLI of proliferation in the SeV group was markedly less than the UV-SeV group. In primary cultured OSNs infected by SeV, the percentage of cells responding to mixed odors was markedly lower in the SeV group compared to UV-SeV (P = 0.007.We

  15. CNPase Expression in Olfactory Ensheathing Cells

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    Christine Radtke

    2011-01-01

    Full Text Available A large body of work supports the proposal that transplantation of olfactory ensheathing cells (OECs into nerve or spinal cord injuries can promote axonal regeneration and remyelination. Yet, some investigators have questioned whether the transplanted OECs associate with axons and form peripheral myelin, or if they recruit endogenous Schwann cells that form myelin. Olfactory bulbs from transgenic mice expressing the enhanced green fluorescent protein (eGFP under the control of the 2-3-cyclic nucleotide 3-phosphodiesterase (CNPase promoter were studied. CNPase is expressed in myelin-forming cells throughout their lineage. We examined CNPase expression in both in situ in the olfactory bulb and in vitro to determine if OECs express CNPase commensurate with their myelination potential. eGFP was observed in the outer nerve layer of the olfactory bulb. Dissociated OECs maintained in culture had both intense eGFP expression and CNPase immunostaining. Transplantation of OECs into transected peripheral nerve longitudinally associated with the regenerated axons. These data indicate that OECs in the outer nerve layer of the olfactory bulb of CNPase transgenic mice express CNPase. Thus, while OECs do not normally form myelin on olfactory nerve axons, their expression of CNPase is commensurate with their potential to form myelin when transplanted into injured peripheral nerve.

  16. Olfactory deficits in boys with cleft palate.

    Science.gov (United States)

    Richman, R A; Sheehe, P R; McCanty, T; Vespasiano, M; Post, E M; Guzi, S; Wright, H

    1988-12-01

    An odor identification task was used to determine whether individuals with cleft palate (with or without cleft lip) also have an increased prevalence of olfactory deficits. Olfactory responses of 35 affected subjects (7 to 22 years of age) were compared with those of 68 subjects of comparable age without cleft palates. Subjects were requested to identify the smell of ten common household odors. They selected their responses from an alphabetized list of the test odorants. After a practice trial, the set of odorants was presented five times in randomized sequences. The percentage of correct responses increased with age for prepubertal and pubertal subjects without cleft palates. Although the olfactory scores of girls without cleft palates continued to increase after puberty, this trend was absent in boys. On the average, the girls with cleft palates, compared with only three of 34 boys without cleft palates, had olfactory scores less than 60% correct. There was no evidence of heterogeneity in the magnitude or direction of the relationship between any of the subtypes of cleft palate and olfactory dysfunction. In this study, cleft palate is more strongly associated with olfactory deficits in boys than in girls, suggesting the possibility that the deficit may be a sex-influenced trait.

  17. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Science.gov (United States)

    Challis, Rosemary C; Tian, Huikai; Yin, Wenbin; Ma, Minghong

    2016-01-01

    We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII), a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE) 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter) and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found), similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice) have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  18. Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

    Directory of Open Access Journals (Sweden)

    Rosemary C Challis

    Full Text Available We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII, a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found, similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

  19. Relation of the volume of the olfactory bulb to psychophysical measures of olfactory function.

    Science.gov (United States)

    Mazal, Patricia Portillo; Haehner, Antje; Hummel, Thomas

    2016-01-01

    The aim of this review is to investigate whether changes in olfactory bulb volume relate to changes in specific olfactory functions. We studied currently available peer-reviewed articles on the volume of the human olfactory bulb that also included a psychophysical measure of olfactory function. In the present review, we observed a very clear and consistent correlation between general olfactory function and olfactory bulb (OB) volume. We were not able to find a clear relationship between a specific smell component and OB volume, even when analyzing pathologic conditions separately. In some cases, changes were observed for different subtests, but these changes did not significantly correlate with OB volume or had only a borderline correlation. In other cases, we found contradictory data. Several factors may contribute to the difficulties in finding correlations with the different components of smell: (1) the OB volume may be influenced by information from olfactory receptor neurons (bottom-up effect), information from central nervous system (top-down effect) and by direct damage; (2) most pathologic conditions affect more than one area of the olfactory pathway; (3) small sample sizes of hyposmic subjects were used. We believe that it is necessary to do further studies with larger numbers of subjects to answer the currently investigated question.

  20. Olfactory imprinting is correlated with changes in gene expression in the olfactory epithelia of the zebrafish.

    Science.gov (United States)

    Harden, Maegan V; Newton, Lucy A; Lloyd, Russell C; Whitlock, Kathleen E

    2006-11-01

    Odors experienced as juveniles can have significant effects on the behavior of mature organisms. A dramatic example of this occurs in salmon, where the odors experienced by developing fish determine the river to which they return as adults. Further examples of olfactory memories are found in many animals including vertebrates and invertebrates. Yet, the cellular and molecular bases underlying the formation of olfactory memory are poorly understood. We have devised a series of experiments to determine whether zebrafish can form olfactory memories much like those observed in salmonids. Here we show for the first time that zebrafish form and retain olfactory memories of an artificial odorant, phenylethyl alcohol (PEA), experienced as juveniles. Furthermore, we demonstrate that exposure to PEA results in changes in gene expression within the olfactory sensory system. These changes are evident by in situ hybridization in the olfactory epithelium of the developing zebrafish. Strikingly, our analysis by in situ hybridization demonstrates that the transcription factor, otx2, is up regulated in the olfactory sensory epithelia in response to PEA. This increase is evident at 2-3 days postfertilization and is maintained in the adult animals. We propose that the changes in otx2 gene expression are manifest as an increase in the number of neuronal precursors in the cells olfactory epithelium of the odor-exposed fish. Thus, our results reveal a role for the environment in controlling gene expression in the developing peripheral nervous system. Copyright 2006 Wiley Periodicals, Inc.

  1. Olfactory processing and odor specificity: a meta-analysis of menstrual cycle variation in olfactory sensitivity

    Directory of Open Access Journals (Sweden)

    Martinec Nováková Lenka

    2014-12-01

    Full Text Available Cycle-correlated variation in olfactory threshold, with women becoming more sensitive to odors mid-cycle, is somewhat supported by the literature but the evidence is not entirely consistent, with several studies finding no, or mixed, effects. It has been argued that cyclic shifts in olfactory threshold might be limited to odors relevant to the mating context.

  2. A mutation in the pericentrin gene causes abnormal interneuron migration to the olfactory bulb in mice.

    Science.gov (United States)

    Endoh-Yamagami, Setsu; Karkar, Kameel M; May, Scott R; Cobos, Inma; Thwin, Myo T; Long, Jason E; Ashique, Amir M; Zarbalis, Konstantinos; Rubenstein, John L R; Peterson, Andrew S

    2010-04-01

    Precise control of neuronal migration is essential for proper function of the brain. Taking a forward genetic screen, we isolated a mutant mouse with defects in interneuron migration. By genetic mapping, we identified a frame shift mutation in the pericentrin (Pcnt) gene. The Pcnt gene encodes a large centrosomal coiled-coil protein that has been implicated in schizophrenia. Recently, frame shift and premature termination mutations in the pericentrin (PCNT) gene were identified in individuals with Seckel syndrome and microcephalic osteodysplastic primordial dwarfism (MOPD II), both of which are characterized by greatly reduced body and brain sizes. The mouse Pcnt mutant shares features with the human syndromes in its overall growth retardation and reduced brain size. We found that dorsal lateral ganglionic eminence (dLGE)-derived olfactory bulb interneurons are severely affected and distributed abnormally in the rostral forebrain in the mutant. Furthermore, mutant interneurons exhibit abnormal migration behavior and RNA interference knockdown of Pcnt impairs cell migration along the rostal migratory stream (RMS) into the olfactory bulb. These findings indicate that pericentrin is required for proper migration of olfactory bulb interneurons and provide a developmental basis for association of pericentrin function with interneuron defects in human schizophrenia. Copyright 2009 Elsevier Inc. All rights reserved.

  3. Olfactory Assessment of Competitors to the Nest Site: An Experiment on a Passerine Species.

    Directory of Open Access Journals (Sweden)

    Matteo Griggio

    Full Text Available Since most avian species have been considered anosmic or microsmatic, olfaction and associated behavioural patterns have hardly been investigated. Most importantly, empirical data on avian olfaction is not equally distributed among species. Initial investigations focused on species with relatively big olfactory bulbs because they were thought to have better olfactory capabilities. Hence, in this study we tested the ability of house sparrows (Passer domesticus to use chemical cues as parameters to estimate nest features. House sparrows are a commonly used model species, but their olfactory capabilities have not been studied so far. We offered two different odours to males and females, namely the scent of mouse urine (Mus musculus domesticus, representing a possible competitor and a threat to eggs and hatchlings, and the odour of hay, representing a familiar and innocuous odour. The experiment was performed at the sunset to simulate a first inspection to new possible roosting or nesting sites. Interestingly, males but not females preferred to spend significantly more time in front of the hay odour, than in front of the scent of mouse urine. Our results strengthen the hypothesis that oscines can not only perceive odours but also use olfaction to assess the environment and estimate nest site quality.

  4. Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels.

    Science.gov (United States)

    Kapoor, Vikrant; Provost, Allison C; Agarwal, Prateek; Murthy, Venkatesh N

    2016-02-01

    The serotonergic raphe nuclei are involved in regulating brain states over timescales of minutes and hours. We examined more rapid effects of raphe activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels.

  5. Involvement of TRPV1 in the Olfactory Bulb in Rimonabant-Induced Olfactory Discrimination Deficit.

    Science.gov (United States)

    Hu, Sherry Shu-Jung

    2016-02-29

    Rimonabant is well recognized as a cannabinoid CB₁ receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB₁ receptors, it also exerts several pharmacological and behavioral effects independent of CB₁ receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1). Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution. Interestingly, CB₁ receptor has recently been suggested to play a role in olfactory functions. Olfaction not only is involved in food intake, visual perception and social interaction, but also is proposed as a putative marker for schizophrenia and autism. Therefore, the present study aimed to investigate whether CB₁ receptor and TRPV1 played a role in olfactory functions. We first used the genetic disruption approach to examine the role of CB₁ receptor in olfactory functions and found that CB₁ knockout mice exhibited olfactory discrimination deficit. However, it is important to point out that these CB₁ knockout mice, despite their normal locomotivity, displayed deficiencies in the olfactory foraging and novel object exploration tasks. These results imply that general exploratory behaviors toward odorant and odorless objects are compromised in CB₁ knockout mice. We next turned to the pharmacological approach to examine the role of CB₁ receptor and TRPV1 in olfactory functions. We found that the short-term administration of rimonabant, injected systemically or directly into the olfactory bulb (OB), impaired olfactory discrimination that was rescued by the TRPV1 antagonist capsazepine (CPZ), via the same route of rimonabant, in wild-type mice. These results suggest that TRPV1 in the OB is involved in rimonabant-induced olfactory discrimination deficit. However, the

  6. MicroRNA expression in the adult mouse central nervous system

    DEFF Research Database (Denmark)

    Bak, Mads; Silahtaroglu, Asli; Møller, Morten

    2008-01-01

    , hypothalamus, hippocampus, neocortex, olfactory bulb, eye, and pituitary gland. These findings suggest that a large number of mouse CNS-expressed miRNAs may be associated with specific functions within these regions. Notably, more than 50% of the identified mouse CNS-enriched miRNAs showed different expression...

  7. The Development of Olfactory Organ of Lissotriton Vulgaris (Amphibia, Caudata)

    National Research Council Canada - National Science Library

    M F Kovtun; Ya V Stepanyuk

    2015-01-01

      The Development of Olfactory Organ of Lissotriton vulgaris (Amphibia, Caudata). Kovtun, M. F, Stepanyuk, Ya. V. - Using common histological methods, the morphogenesis of olfactory analyzer peripheral part of Lissotriton vulgaris...

  8. The Development of Olfactory Organ of Lissotriton Vulgaris (Amphibia, Caudata)

    National Research Council Canada - National Science Library

    M. F. Kovtun; Ya. V. Stepanyuk

    2015-01-01

    The Development of Olfactory Organ of Lissotriton vulgaris (Amphibia, Caudata). Kovtun, M. F, Stepanyuk, Ya. V. - Using common histological methods, the morphogenesis of olfactory analyzer peripheral part of Lissotriton vulgaris...

  9. Zicam-induced damage to mouse and human nasal tissue.

    Directory of Open Access Journals (Sweden)

    Jae H Lim

    Full Text Available Intranasal medications are used to treat various nasal disorders. However, their effects on olfaction remain unknown. Zicam (zinc gluconate; Matrixx Initiatives, Inc, a homeopathic substance marketed to alleviate cold symptoms, has been implicated in olfactory dysfunction. Here, we investigated Zicam and several common intranasal agents for their effects on olfactory function. Zicam was the only substance that showed significant cytotoxicity in both mouse and human nasal tissue. Specifically, Zicam-treated mice had disrupted sensitivity of olfactory sensory neurons to odorant stimulation and were unable to detect novel odorants in behavioral testing. These findings were long-term as no recovery of function was observed after two months. Finally, human nasal explants treated with Zicam displayed significantly elevated extracellular lactate dehydrogenase levels compared to saline-treated controls, suggesting severe necrosis that was confirmed on histology. Our results demonstrate that Zicam use could irreversibly damage mouse and human nasal tissue and may lead to significant smell dysfunction.

  10. Spatial patterns of gene expression in the olfactory bulb

    OpenAIRE

    Lin, David M.; Yang, Yee Hwa; Scolnick, Jonathan A.; Brunet, Lisa J.; Marsh, Heather; Peng, Vivian; Okazaki, Yasushi; Hayashizaki, Yoshihide; Speed, Terence P.; Ngai, John

    2004-01-01

    How olfactory sensory neurons converge on spatially invariant glomeruli in the olfactory bulb is largely unknown. In one model, olfactory sensory neurons interact with spatially restricted guidance cues in the bulb that orient and guide them to their target. Identifying differentially expressed molecules in the olfactory bulb has been extremely difficult, however, hindering a molecular analysis of convergence. Here, we describe several such genes that have been identified in a screen that com...

  11. [Olfactory esthesioneuroma manifesting as Schwartz-Bartter syndrome].

    Science.gov (United States)

    Bernard, P; Vitrey, D; Boursier, C; Brunot, J; Fléchaire, A

    2000-03-01

    Olfactory esthesioneuroblastoma is an uncommon neuroectodermal tumor originating from the olfactory epithelium, which is rarely associated with hormone excess syndrome. Asymptomatic olfactory esthesioneuroblastoma was diagnosed in a 22-year-old man who presented a syndrome of inappropriate antidiuretic hormone secretion. Following surgery, the immunohistochemical analysis demonstrated the existence of neurophysin hormone in tumoral cells. This case provides evidence that olfactory esthesioneuroblastoma can be uncovered by inappropriate antidiuretic hormone secretion.

  12. Olfactory region schwannoma: Excision with preservation of olfaction

    Directory of Open Access Journals (Sweden)

    Pravin Salunke

    2014-01-01

    Full Text Available Olfactory region schwannomas are rare, but when they occur, they commonly arise from the meningeal branches of the trigeminal nerve and may present without involvement of the olfaction. A 24 year old lady presented with hemifacial paraesthesias. Radiology revealed a large olfactory region enhancing lesion. She was operated through a transbasal with olfactory preserving approach. This manuscript highlights the importance of olfactory preservation in such lesions.

  13. Self-Ratings of Olfactory Function Reflect Odor Annoyance Rather than Olfactory Acuity

    DEFF Research Database (Denmark)

    Knaapila, Antti; Tuorila, Hely; Kyvik, Kirsten

    2008-01-01

    OBJECTIVE/HYPOTHESIS:: Self-ratings of olfactory function correlates often poorly with results of objective smell tests. We explored them relative to self-rating of odor annoyance, to odor identification ability, and to mean perceived intensity of odors, and estimated relative genetic and environ......OBJECTIVE/HYPOTHESIS:: Self-ratings of olfactory function correlates often poorly with results of objective smell tests. We explored them relative to self-rating of odor annoyance, to odor identification ability, and to mean perceived intensity of odors, and estimated relative genetic...... Kingdom rated their sense of smell and annoyance caused by ambient smells (e.g., smells of foods) using seven categories, and performed odor identification and evaluation task for six scratch-and-sniff odor stimuli. RESULTS:: The self-rating of olfactory function correlated with the self-rating of odor......-rating of olfactory function and support earlier findings of discrepancy between subjective and objective measures of olfactory function. In addition, the results imply that the self-rating of olfactory function arises from experienced odor annoyance rather than from actual olfactory acuity....

  14. Neural Correlates of Olfactory Learning: Critical Role of Centrifugal Neuromodulation

    Science.gov (United States)

    Fletcher, Max L.; Chen, Wei R.

    2010-01-01

    The mammalian olfactory system is well established for its remarkable capability of undergoing experience-dependent plasticity. Although this process involves changes at multiple stages throughout the central olfactory pathway, even the early stages of processing, such as the olfactory bulb and piriform cortex, can display a high degree of…

  15. Odorant organization in the olfactory bulb of the sea lamprey.

    Science.gov (United States)

    Green, Warren W; Boyes, Karl; McFadden, Charrie; Daghfous, Gheylen; Auclair, François; Zhang, Huiming; Li, Weiming; Dubuc, Réjean; Zielinski, Barbara S

    2017-04-01

    Olfactory sensory neurons innervate the olfactory bulb, where responses to different odorants generate a chemotopic map of increased neural activity within different bulbar regions. In this study, insight into the basal pattern of neural organization of the vertebrate olfactory bulb was gained by investigating the lamprey. Retrograde labelling established that lateral and dorsal bulbar territories receive the axons of sensory neurons broadly distributed in the main olfactory epithelium and that the medial region receives sensory neuron input only from neurons projecting from the accessory olfactory organ. The response duration for local field potential recordings was similar in the lateral and dorsal regions, and both were longer than medial responses. All three regions responded to amino acid odorants. The dorsal and medial regions, but not the lateral region, responded to steroids. These findings show evidence for olfactory streams in the sea lamprey olfactory bulb: the lateral region responds to amino acids from sensory input in the main olfactory epithelium, the dorsal region responds to steroids (taurocholic acid and pheromones) and to amino acids from sensory input in the main olfactory epithelium, and the medial bulbar region responds to amino acids and steroids stimulating the accessory olfactory organ. These findings indicate that olfactory subsystems are present at the base of vertebrate evolution and that regionality in the lamprey olfactory bulb has some aspects previously seen in other vertebrate species. © 2017. Published by The Company of Biologists Ltd.

  16. Individual olfactory perception reveals meaningful nonolfactory genetic information.

    Science.gov (United States)

    Secundo, Lavi; Snitz, Kobi; Weissler, Kineret; Pinchover, Liron; Shoenfeld, Yehuda; Loewenthal, Ron; Agmon-Levin, Nancy; Frumin, Idan; Bar-Zvi, Dana; Shushan, Sagit; Sobel, Noam

    2015-07-14

    Each person expresses a potentially unique subset of ∼ 400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10(-4)), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10(-6)). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

  17. Does post-infectious olfactory loss affect mood more severely than chronic sinusitis with olfactory loss?

    Science.gov (United States)

    Jung, Yong G; Lee, Jun-Seok; Park, Gi C

    2014-11-01

    Olfactory deficits that develop after viral upper respiratory infection (URI) may have different effects on patient depression index compared to chronic sinusitis with olfactory loss. However, there have been no controlled trials to evaluate the different effects of chronic sinusitis and URI on depression index. Prospective study of 25 subjects in two groups. This study enrolled 25 participants who were diagnosed with post-URI olfactory loss as the study group and 25 patients with chronic sinusitis and olfactory loss as a control group. Control group participants were matched for age, sex, and degree of olfactory loss (threshold, discrimination, and identification [TDI]). We compared the Beck Depression Inventory (BDI) scores of each group and analyzed the correlation between TDI and BDI. The mean BDI score of the post-URI group was significantly higher than that of the control group (14.52 ± 6.59 vs. 9.32 ± 5.23; P=.002). Age, sex, and TDI score did not affect BDI score in the post-URI olfactory loss group. However, BDI score in the sinusitis group was inversely correlated with TDI score (R=-0.423; P=.035), and the BDI score of female subjects (11.00 ± 5.13) was significantly higher than that of male subjects (5.00 ± 2.16; P = .047). Post-URI olfactory loss affected patient mood more severely than chronic sinusitis with a similar degree of olfactory loss. This influence was not affected by sex, age, or TDI score in the post-URI olfactory loss group. 3b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Traumatic brain injury and olfactory deficits

    DEFF Research Database (Denmark)

    Fortin, Audrey; Lefebvre, Mathilde Beaulieu; Ptito, Maurice

    2010-01-01

    PRIMARY OBJECTIVE: Olfactory functions are not systematically evaluated following traumatic brain injury (TBI). This study aimed at comparing two smell tests that are used in a clinical setting. RESEARCH DESIGN: The University of Pennsylvania Smell Identification Test (UPSIT) and the Alberta Smell...... Test were compared in terms of assessment time, cost and diagnosis. Parameters associated with olfactory loss such as injury severity, type of cerebral lesion and depressive data were considered. Forty-nine TBI patients admitted to an outpatient rehabilitation programme took part in this experiment....... RESULTS: The scores of the two smell tests were significantly correlated. Both tests indicated that patients with frontal lesion performed significantly worse than patients with other types of lesion. Mood and injury severity were not associated with olfactory impairment when age was taken into account...

  19. Olfactory coding in the turbulent realm.

    Directory of Open Access Journals (Sweden)

    Vincent Jacob

    2017-12-01

    Full Text Available Long-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs and antennal lobe projection neurons (PNs to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear-nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.

  20. Olfactory coding in the turbulent realm.

    Science.gov (United States)

    Jacob, Vincent; Monsempès, Christelle; Rospars, Jean-Pierre; Masson, Jean-Baptiste; Lucas, Philippe

    2017-12-01

    Long-distance olfactory search behaviors depend on odor detection dynamics. Due to turbulence, olfactory signals travel as bursts of variable concentration and spacing and are characterized by long-tail distributions of odor/no-odor events, challenging the computing capacities of olfactory systems. How animals encode complex olfactory scenes to track the plume far from the source remains unclear. Here we focus on the coding of the plume temporal dynamics in moths. We compare responses of olfactory receptor neurons (ORNs) and antennal lobe projection neurons (PNs) to sequences of pheromone stimuli either with white-noise patterns or with realistic turbulent temporal structures simulating a large range of distances (8 to 64 m) from the odor source. For the first time, we analyze what information is extracted by the olfactory system at large distances from the source. Neuronal responses are analyzed using linear-nonlinear models fitted with white-noise stimuli and used for predicting responses to turbulent stimuli. We found that neuronal firing rate is less correlated with the dynamic odor time course when distance to the source increases because of improper coding during long odor and no-odor events that characterize large distances. Rapid adaptation during long puffs does not preclude however the detection of puff transitions in PNs. Individual PNs but not individual ORNs encode the onset and offset of odor puffs for any temporal structure of stimuli. A higher spontaneous firing rate coupled to an inhibition phase at the end of PN responses contributes to this coding property. This allows PNs to decode the temporal structure of the odor plume at any distance to the source, an essential piece of information moths can use in their tracking behavior.

  1. Inhibitory neurotransmission and olfactory memory in honeybees.

    Science.gov (United States)

    El Hassani, Abdessalam Kacimi; Giurfa, Martin; Gauthier, Monique; Armengaud, Catherine

    2008-11-01

    In insects, gamma-aminobutyric acid (GABA) and glutamate mediate fast inhibitory neurotransmission through ligand-gated chloride channel receptors. Both GABA and glutamate have been identified in the olfactory circuit of the honeybee. Here we investigated the role of inhibitory transmission mediated by GABA and glutamate-gated chloride channels (GluCls) in olfactory learning and memory in honeybees. We combined olfactory conditioning with injection of ivermectin, an agonist of GluCl receptors. We also injected a blocker of glutamate transporters (L-trans-PDC) or a GABA analog (TACA). We measured acquisition and retention 1, 24 and 48 h after the last acquisition trial. A low dose of ivermectin (0.01 ng/bee) impaired long-term olfactory memory (48 h) while a higher dose (0.05 ng/bee) had no effect. Double injections of ivermectin and L-trans-PDC or TACA had different effects on memory retention, depending on the doses and agents combined. When the low dose of ivermectin was injected after Ringer, long-term memory was again impaired (48 h). Such an effect was rescued by injection of both TACA and L-trans-PDC. A combination of the higher dose of ivermectin and TACA decreased retention at 48 h. We interpret these results as reflecting the involvement of both GluCl and GABA receptors in the impairment of olfactory long-term memory induced by ivermectin. These results illustrate the diversity of inhibitory transmission and its implication in long-term olfactory memory in honeybees.

  2. Linking adult olfactory neurogenesis to social behavior

    Directory of Open Access Journals (Sweden)

    Claudia E Feierstein

    2012-11-01

    Full Text Available In the adult brain, new neurons are added to two brain areas: the olfactory bulb and the hippocampus. Newly-generated neurons integrate into the preexisting circuits, bringing a set of unique properties, such as increased plasticity and responsiveness to stimuli. However, the functional implications of the constant addition of these neurons remain unclear, although they are believed to be important for learning and memory. The levels of neurogenesis are regulated by a variety of environmental factors, as well as during learning, suggesting that new neurons could be important for coping with changing environmental demands. Notably, neurogenesis has been shown to be physiologically regulated in relation to reproductive behavior: neurogenesis increases in female mice upon exposure to cues of the mating partners, during pregnancy and lactation, and in male mice upon exposure to their offspring. In this scenario, and because of the key contribution of olfaction to maternal behavior, we sought to investigate the contribution of adult-generated neurons in the olfactory system to maternal behavior and offspring recognition. To do so, we selectively disrupted neurogenesis in the olfactory pathway of female mice using focal irradiation. Disruption of adult neurogenesis in the olfactory bulb did not affect maternal behavior, or the ability of female mice to discriminate familiar from unfamiliar pups. However, reduction of olfactory neurogenesis resulted in abnormal social interaction of female mice, specifically with male conspecifics. Because the olfactory system is crucial for sex recognition, we suggest that the abnormal interaction with males could result from the inability to detect or discriminate male-specific odors and could therefore have implications for the recognition of potential mating partners. Here, I review the results of this and other studies, and discuss their implications for our understanding of the function of adult neurogenesis.

  3. Zinc-finger gene Fez in the olfactory sensory neurons regulates development of the olfactory bulb non-cell-autonomously.

    Science.gov (United States)

    Hirata, Tsutomu; Nakazawa, Masato; Yoshihara, Sei-ichi; Miyachi, Hitoshi; Kitamura, Kunio; Yoshihara, Yoshihiro; Hibi, Masahiko

    2006-04-01

    Fez is a zinc-finger gene encoding a transcriptional repressor that is expressed in the olfactory epithelium, hypothalamus, ventrolateral pallium and prethalamus at mid-gestation. To reveal its function, we generated Fez-deficient mice. The Fez-deficient mice showed several abnormalities in the olfactory system: (1) impaired axonal projection of the olfactory sensory neurons; (2) reduced size of the olfactory bulb; (3) abnormal layer formation in the olfactory bulb; and (4) aberrant rostral migration of the interneuron progenitors. Fez was not expressed in the projection neurons, interneurons or interneuron progenitors. Transgene-mediated expression of Fez in olfactory sensory neurons significantly rescued the abnormalities in olfactory axon projection and in the morphogenesis of the olfactory bulb in Fez-knockout mice. Thus, Fez is cell-autonomously required for the axon termination of olfactory sensory neurons, and Fez non-cell-autonomously controls layer formation and interneuron development in the olfactory bulb. These findings suggest that signals from olfactory sensory neurons contribute to the proper formation of the olfactory bulb.

  4. Measuring Olfactory Processes in Mus musculus.

    Science.gov (United States)

    Schellinck, Heather

    2017-09-04

    This paper briefly reviews the literature that describes olfactory acuity and odour discrimination learning. The results of current studies that examined the role of the neurotransmitters noradrenalin and acetylcholine in odour discrimination learning are discussed as are those that investigated pattern recognition and models of human disease. The methodology associated with such work is also described and its role in creating disparate results assessed. Recommendations for increasing the reliability and validity of experiments so as to further our understanding of olfactory processes in both healthy mice and those modelling human disease are made throughout the paper. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The Development of Olfactory Organ of Lissotriton Vulgaris (Amphibia, Caudata

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    Kovtun M. F.

    2015-12-01

    Full Text Available The Development of Olfactory Organ of Lissotriton vulgaris (Amphibia, Caudata. Kovtun, M. F, Stepanyuk, Ya. V. - Using common histological methods, the morphogenesis of olfactory analyzer peripheral part of Lissotriton vulgaris (Amphibia, Caudata was studied, during the developmental period starting with olfactory pit laying and finishing with definitive olfactory organ formation. Special attention is paid to vomeronasal organ and vomeronasal gland development. Reasoning from obtained data, we consider that vomeronasal organ emerged as the result of olfactory epithelium and nasal cavity differentiation.

  6. Olfactory cortical neurons read out a relative time code in the olfactory bulb.

    Science.gov (United States)

    Haddad, Rafi; Lanjuin, Anne; Madisen, Linda; Zeng, Hongkui; Murthy, Venkatesh N; Uchida, Naoshige

    2013-07-01

    Odor stimulation evokes complex spatiotemporal activity in the olfactory bulb, suggesting that both the identity of activated neurons and the timing of their activity convey information about odors. However, whether and how downstream neurons decipher these temporal patterns remains unknown. We addressed this question by measuring the spiking activity of downstream neurons while optogenetically stimulating two foci in the olfactory bulb with varying relative timing in mice. We found that the overall spike rates of piriform cortex neurons (PCNs) were sensitive to the relative timing of activation. Posterior PCNs showed higher sensitivity to relative input times than neurons in the anterior piriform cortex. In contrast, olfactory bulb neurons rarely showed such sensitivity. Thus, the brain can transform a relative time code in the periphery into a firing rate-based representation in central brain areas, providing evidence for the relevance of a relative time-based code in the olfactory bulb.

  7. Olfactory disfunction and its relation olfactory bulb volume in Parkinson's disease.

    Science.gov (United States)

    Altinayar, S; Oner, S; Can, S; Kizilay, A; Kamisli, S; Sarac, K

    2014-01-01

    Olfactory dysfunction is the most frequently seen non-motor symptom of Idiopathic Parkinson's disease (IPD). The aim of this study is to analyze selective olfactory dysfunction, and olfactory bulb volume (OBV) in subtypes of IPD, and compare them with those of the healthy controls. Our study included 41 patients with IPD and age and gender matched 19 healthy controls. IPD patients were either tremor dominant (65.9%; TDPD) or non-tremor dominant (34.1%; NTDPD) type. All patients underwent neurological, ear, nose, and throat examinations, and orthonasal olfaction testing. Magnetic resonance imaging (MRI) technique was used to measure the volume of the olfactory bulb. A significant decrease in olfactory identification scores was found in the patient group. The patients had difficulty in discriminating between odors of mothballs, chocolate, Turkish coffee and soap. OBV did not differ between the patient, and the control groups. In the TDPD group, odor identification ability was decreased when compared to the control group. However, odor test results of NTDPD, control and TDPD groups were similar. OBV estimates of the TDPD group were not different from those of the control group, while in the NTDPD group OBVs were found to be decreased. In all patients with Parkinson's disease OBV values did not vary with age of the patients, duration of the disease, age at onset of the disease, and Unified Parkinson's Disease Rating Scale motor scores (UPDRS-m). Olfactory function is a complex process involving olfactory, and cortical structures as well. In Idiopathic Parkinson's disease, changes in OBV do not seem to be directly related to olfactory dysfunction.

  8. Reversible deafferentation of the adult zebrafish olfactory bulb affects glomerular distribution and olfactory-mediated behavior.

    Science.gov (United States)

    Paskin, Taylor R; Byrd-Jacobs, Christine A

    2012-12-01

    The olfactory system is a useful model for studying central nervous system recovery from damage due to its neuroplasticity. We recently developed a novel method of deafferentation by repeated exposure of Triton X-100 to the olfactory organ of adult zebrafish. This long-term, reversible method of deafferentation allows both degeneration and regeneration to be observed in the olfactory bulb. The aim of the present study is to examine olfactory bulb innervation, glomerular patterns, and olfactory-mediated behavior with repeated Triton X-100 treatment and the potential for recovery following cessation of treatment. Olfactory bulbs of control, chronic-treated, and recovery animals were examined for the presence or absence of glomeruli that have been identified in the zebrafish glomerular map. Following chronic treatment, the number of glomeruli was dramatically reduced; however, partial innervation remained in the lateral region of the bulb. When animals were given time to recover, complete glomerular distribution returned. A behavioral assay was developed to determine if innervation remaining correlated with behavior of the fish. Chronic-treated fish did not respond to odorants involved with social behavior but continued to react to odorants that mediate feeding behavior. Following recovery, responses to odorants involved with social behavior returned. The morphological and behavioral effects of chronic Triton X-100 treatment in the olfactory system suggest there may be differential susceptibility or resistance to external damage in a subset of sensory neurons. The results of this study demonstrate the remarkable regenerative ability of the olfactory system following extensive and long-term injury. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Construction of functional neuronal circuitry in the olfactory bulb.

    Science.gov (United States)

    Imai, Takeshi

    2014-11-01

    Recent studies using molecular genetics, electrophysiology, in vivo imaging, and behavioral analyses have elucidated detailed connectivity and function of the mammalian olfactory circuits. The olfactory bulb is the first relay station of olfactory perception in the brain, but it is more than a simple relay: olfactory information is dynamically tuned by local olfactory bulb circuits and converted to spatiotemporal neural code for higher-order information processing. Because the olfactory bulb processes ∼1000 discrete input channels from different odorant receptors, it serves as a good model to study neuronal wiring specificity, from both functional and developmental aspects. This review summarizes our current understanding of the olfactory bulb circuitry from functional standpoint and discusses important future studies with particular focus on its development and plasticity. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Deconstructing the molecular architecture of olfactory areas using proteomics.

    Science.gov (United States)

    Lachén-Montes, Mercedes; Fernández-Irigoyen, Joaquín; Santamaría, Enrique

    2016-12-01

    The anatomy of the olfactory system is highly complex, comprising a system of olfactory receptors, pathways for the transmission of olfactory information, and structures for the recognition, discrimination, and memorization of odors. During the last years, proteomics has emerged as a large-scale comprehensive approach to characterize and quantify specific olfactory-related proteomes in different biological conditions such as olfactory learning, neurodegeneration, and ageing between others. The current work reviews recent applications of proteomics to olfaction with particular focus on quantitative proteome profiling studies performed on olfactory areas from laboratory animal models as well as proteomic characterizations performed on specific brain structures and fluids involved in human smell. Finally, we will also discuss the potential application of proteomics to study global proteome dynamics and posttranslationally modified proteomes in order to unravel cell-signaling networks that occur from peripheral structures to olfactory cortical areas during odor processing. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Lateralized differences in olfactory function and olfactory bulb volume relate to nasal septum deviation.

    Science.gov (United States)

    Altundag, Aytug; Salihoglu, Murat; Tekeli, Hakan; Saglam, Muzaffer; Cayonu, Melih; Hummel, Thomas

    2014-03-01

    One of the most common reasons for partial nasal obstruction is nasal septal deviation (NSD). The effect of a partial lateralized nasal obstruction on olfactory bulb (OB) volume remains unclear. Thus, the aim of this study was to investigate the side differences in olfactory function and OB in patients with serious NSD. Sixty-five volunteers were included: 22 patients with serious right NSD and 43 patients with left NSD. The patients' mean age was 22 years. All participants received volumetric magnetic resonance imaging scans of the entire brain and detailed lateralized olfactory tests. The majority of the patients exhibited an overall decreased olfactory function (as judged for the better nostril: functional anosmia in 3%, hyposmia in 72%, normosmia in 25%), which seems to be mostly due to the overall severe changes in nasal anatomy. As expected, olfactory function was significantly lower at the narrower side as indicated for odor thresholds, odor discrimination, and odor identification (P ≤ 0.005). When correlating relative scores and volumes (wider minus narrower side), a significantly positive correlation between the relative measures emerged for OB volume and odor identification, odor discrimination, and odor thresholds. Our study clearly highlights that septal deviation results in decreased olfactory function at the narrower side.

  12. The diversified function and potential therapy of ectopic olfactory receptors in non-olfactory tissues.

    Science.gov (United States)

    Chen, Zhe; Zhao, Hong; Fu, Nian; Chen, Linxi

    2017-03-24

    Olfactory receptors (ORs) are mainly distributed in olfactory neurons and play a key role in detecting volatile odorants, eventually resulting in the production of smell perception. Recently, it is also reported that ORs are expressed in non-olfactory tissues including heart, lung, sperm, skin, and cancerous tissues. Interestingly, ectopic ORs are associated with the development of diseases in non-olfactory tissues. For instance, ectopic ORs initiate the hypoxic ventilatory responses and maintain the oxygen homeostasis of breathing in the carotid body when oxygen levels decline. Ectopic ORs induce glucose homeostasis in diabetes. Ectopic ORs regulate systemic blood pressure by increasing renin secretion and vasodilation. Ectopic ORs participate in the process of tumor cell proliferation, apoptosis, metastasis, and invasiveness. Ectopic ORs accelerate the occurrence of obesity, angiogenesis and wound-healing processes. Ectopic ORs affect fetal hemoglobin levels in sickle cell anemia and thalassemia. Finally, we also elaborate some ligands targeting for ORs. Obviously, the diversified function and related signal pathway of ectopic ORs may play a potential therapeutic target in non-olfactory tissues. Thus, this review focuses on the latest research results about the diversified function and therapeutic potential of ectopic ORs in non-olfactory tissues. © 2017 Wiley Periodicals, Inc.

  13. Functional Neuroanatomy of "Drosophila" Olfactory Memory Formation

    Science.gov (United States)

    Guven-Ozkan, Tugba; Davis, Ronald L.

    2014-01-01

    New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying "Drosophila" learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive…

  14. Spotlight on olfactory dysfunction in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rodríguez-Violante M

    2017-06-01

    Full Text Available Mayela Rodríguez-Violante,1,2 Natalia Ospina-García,1,2 Christian Pérez-Lohman,1,2 Amin Cervantes-Arriaga1,2 1Movement Disorders Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico; 2Clinical Neurodegenerative Research Unit, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Abstract: Olfactory dysfunction is frequent in Parkinson’s disease (PD. A correlation between olfactory dysfunction and the pathophysiological process of the disease has been confirmed. On the other hand, olfaction disturbances are also prevalent in other neurodegenerative diseases, and may be related to other factors such as gender, age, smoking, and trauma. Clinically, hyposmia is commonly assessed by smell identification testing. Good diagnostic accuracy has been widely reported, but differences in sensitivity and specificity due to sociocultural factors have also been reported. Since hyposmia may be present before the onset of motor symptoms, it has the potential to serve as a biomarker for the identification of subjects at risk of developing PD. Several studies have been conducted to assess the utility of smell testing as an isolated or combined biomarker for this end. Finally, severe olfactory dysfunction has been associated with faster disease progression and higher risk of cognitive decline in patients with PD. Olfactory dysfunction assessment in PD will continue to be relevant in research and clinical practice. Keywords: Parkinson’s disease, olfaction, smell identification test, biomarker 

  15. Neural crest origin of olfactory ensheating glia.

    NARCIS (Netherlands)

    Barraud, P; Seferiadis, A.A.; Tyson, L.D.; Zwart, M.F.; Szabo-Rogers, H.L.; Ruhrberg, C; Liu, K.J.; Baker, C.V.

    2010-01-01

    Olfactory ensheathing cells (OECs) are a unique class of glial cells with exceptional translational potential because of their ability to support axon regeneration in the central nervous system. Although OECs are similar in many ways to immature and nonmyelinating Schwann cells, and can myelinate

  16. Olfactory receptors in non-chemosensory tissues

    Directory of Open Access Journals (Sweden)

    NaNa Kang & JaeHyung Koo*

    2012-11-01

    Full Text Available Olfactory receptors (ORs detect volatile chemicals that lead tothe initial perception of smell in the brain. The olfactory receptor(OR is the first protein that recognizes odorants in theolfactory signal pathway and it is present in over 1,000 genesin mice. It is also the largest member of the G protein-coupledreceptors (GPCRs. Most ORs are extensively expressed in thenasal olfactory epithelium where they perform the appropriatephysiological functions that fit their location. However, recentwhole-genome sequencing shows that ORs have been foundoutside of the olfactory system, suggesting that ORs may playan important role in the ectopic expression of non-chemosensorytissues. The ectopic expressions of ORs and their physiologicalfunctions have attracted more attention recently sinceMOR23 and testicular hOR17-4 have been found to be involvedin skeletal muscle development, regeneration, and humansperm chemotaxis, respectively. When identifying additionalexpression profiles and functions of ORs in non-olfactorytissues, there are limitations posed by the small number ofantibodies available for similar OR genes. This review presentsthe results of a research series that identifies ectopic expressionsand functions of ORs in non-chemosensory tissues toprovide insight into future research directions.

  17. Olfactory Environment Design for Human Spaceflight

    Science.gov (United States)

    Welch, C. S.; Holland, F. J.

    2002-01-01

    Smell is usually deemed the least important of the five senses. To contradict this assertion, however, there is no shortage of scientific literature which concludes that olfaction is of very great significance to humans. Odours have been shown to have a variety of effects on humans, and are capable of changing both behaviour and cognitive processing in ways that we are frequently completely unconscious of. Examples of this include alertness, alteration of mood, capacity for ideation and intellectual performance. To date, the design of human spacecraft has concentrated on making their olfactory environments, where possible, `odour neutral' - that is ensuring that all unpleasant and/or offensive odours are removed. Here it suggested that spacecraft (and other extraterrestrial facilities for human inhabitation) might benefit from having their olfactory environments designed to be `odour positive', that is to use odours and olfaction for the positive benefit of their residents. This paper presents a summary of current olfactory research and considers both its positive and negative implications for humans in space. It then discusses `odour positive' design of spacecraft olfactory environments and the possible benefits accruing from this approach before examining its implications for the architecture of spacecraft environmental control systems.

  18. Olfactory perception, cognition, and dysfunction in humans.

    Science.gov (United States)

    Stevenson, Richard J

    2013-05-01

    The main functions of olfaction relate to finding food, avoiding predators and disease, and social communication. Its role in detecting food has resulted in a unique dual mode sensory system. Environmental odorants are 'smelled' via the external nostrils, while volatile chemicals in food-detected by the same receptors-arrive via the nasopharynx, contributing to flavor. This arrangement allows the brain to link the consequences of eating with a food's odor, and then later to use this information in the search for food. Recognizing an odorant-a food, mate, or predator-requires the detection of complex chemical blends against a noisy chemical background. The brain solves this problem in two ways. First, by rapid adaptation to background odorants so that new odorants stand out. Second, by pattern matching the neural representation of an odorant to prior olfactory experiences. This account is consistent with olfactory sensory physiology, anatomy, and psychology. Odor perception, and its products, may be subject to further processing-olfactory cognition. While olfactory cognition has features in common with visual or auditory cognition, several aspects are unique, and even those that are common may be instantiated in different ways. These differences can be productively used to evaluate the generality of models of cognition and consciousness. Finally, the olfactory system can breakdown, and this may be predictive of the onset of neurodegenerative conditions such as Alzheimer's, as well as having prognostic value in other disorders such as schizophrenia. WIREs Cogn Sci 2013, 4:273-284. doi: 10.1002/wcs.1224 For further resources related to this article, please visit the WIREs website. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Molecular recognition of ketamine by a subset of olfactory G protein–coupled receptors

    Science.gov (United States)

    Saven, Jeffery G.; Matsunami, Hiroaki; Eckenhoff, Roderic G.

    2015-01-01

    Ketamine elicits various neuropharmacological effects, including sedation, analgesia, general anesthesia, and antidepressant activity. Through an in vitro screen, we identified four mouse olfactory receptors (ORs) that responded to ketamine. In addition to their presence in the olfactory epithelium, these G protein (heterotrimeric guanine nucleotide–binding protein)–coupled receptors (GPCRs) are distributed throughout the central nervous system. To better understand the molecular basis of the interactions between ketamine and ORs, we used sequence comparison and molecular modeling to design mutations that (i) increased, reduced, or abolished ketamine responsiveness in responding receptors, and (ii) rendered non-responding receptors responsive to ketamine. We showed that olfactory sensory neurons (OSNs) that expressed distinct ORs responded to ketamine in vivo, suggesting that ORs may serve as functional targets for ketamine. The ability to both abolish and introduce responsiveness to ketamine in GPCRs enabled us to identify and confirm distinct interaction loci in the binding site, which suggested a signature ketamine-binding pocket that may guide exploration of additional receptors for this general anesthetic drug. PMID:25829447

  20. Loss of olfactory receptor genes coincides with the acquisition of full trichromatic vision in primates.

    Directory of Open Access Journals (Sweden)

    Yoav Gilad

    2004-01-01

    Full Text Available Olfactory receptor (OR genes constitute the molecular basis for the sense of smell and are encoded by the largest gene family in mammalian genomes. Previous studies suggested that the proportion of pseudogenes in the OR gene family is significantly larger in humans than in other apes and significantly larger in apes than in the mouse. To investigate the process of degeneration of the olfactory repertoire in primates, we estimated the proportion of OR pseudogenes in 19 primate species by surveying randomly chosen subsets of 100 OR genes from each species. We find that apes, Old World monkeys and one New World monkey, the howler monkey, have a significantly higher proportion of OR pseudogenes than do other New World monkeys or the lemur (a prosimian. Strikingly, the howler monkey is also the only New World monkey to possess full trichromatic vision, along with Old World monkeys and apes. Our findings suggest that the deterioration of the olfactory repertoire occurred concomitant with the acquisition of full trichromatic color vision in primates.

  1. Basic principles and molecular mechanisms of olfactory axon pathfinding.

    Science.gov (United States)

    Yoshihara, Y; Mori, K

    1997-11-01

    The present review describes several lines of recent evidence providing new insights into the basic principles and mechanisms of axon projection from the olfactory epithelium to the olfactory bulb. Olfactory sensory neurons are classified into approximately 1000 subtypes according to the expression of specific odorant receptors. Olfactory sensory neurons expressing a given odorant receptor are distributed within one zone out of the four circumscribed zones of the olfactory epithelium and send their axons to the corresponding zone of the olfactory bulb: the principle of zone-to-zone projection. We discuss possible functions of a novel cell adhesion molecule, viz., OCAM, in the formation and maintenance of zone-to-zone projection of both olfactory and vomeronasal axons. Furthermore, olfactory sensory neurons expressing a given odorant receptor converge their axons onto only two topographically fixed glomeruli among the 1500-3000 glomeruli in the olfactory bulb: the principle of glomerular convergence. These axonal connection patterns give rise to the response specificity of the second-order neurons, viz., the mitral/tufted cells, to a particular range of odor molecules. In the process of glomerular convergence, combinatorial functions of axon-associated cell adhesion molecules and odorant receptor proteins may be required for the establishment of the precise targeting of olfactory axons to the appropriate glomeruli.

  2. Anatomical specializations for enhanced olfactory sensitivity in kiwi, Apteryx mantelli.

    Science.gov (United States)

    Corfield, Jeremy R; Eisthen, Heather L; Iwaniuk, Andrew N; Parsons, Stuart

    2014-01-01

    The ability to function in a nocturnal and ground-dwelling niche requires a unique set of sensory specializations. The New Zealand kiwi has shifted away from vision, instead relying on auditory and tactile stimuli to function in its environment and locate prey. Behavioral evidence suggests that kiwi also rely on their sense of smell, using olfactory cues in foraging and possibly also in communication and social interactions. Anatomical studies appear to support these observations: the olfactory bulbs and tubercles have been suggested to be large in the kiwi relative to other birds, although the extent of this enlargement is poorly understood. In this study, we examine the size of the olfactory bulbs in kiwi and compare them with 55 other bird species, including emus, ostriches, rheas, tinamous, and 2 extinct species of moa (Dinornithiformes). We also examine the cytoarchitecture of the olfactory bulbs and olfactory epithelium to determine if any neural specializations beyond size are present that would increase olfactory acuity. Kiwi were a clear outlier in our analysis, with olfactory bulbs that are proportionately larger than those of any other bird in this study. Emus, close relatives of the kiwi, also had a relative enlargement of the olfactory bulbs, possibly supporting a phylogenetic link to well-developed olfaction. The olfactory bulbs in kiwi are almost in direct contact with the olfactory epithelium, which is indeed well developed and complex, with olfactory receptor cells occupying a large percentage of the epithelium. The anatomy of the kiwi olfactory system supports an enhancement for olfactory sensitivities, which is undoubtedly associated with their unique nocturnal niche. © 2014 S. Karger AG, Basel.

  3. Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer.

    Science.gov (United States)

    Veyseller, Bayram; Ozucer, Berke; Degirmenci, Nazan; Gurbuz, Defne; Tambas, Makbule; Altun, Musa; Aksoy, Fadullah; Ozturan, Orhan

    2014-10-01

    Radiotherapy is the primary method of treatment for nasopharyngeal cancer (NPC) and many side effects were reported in patients receiving radiation to this area. This study was conducted to evaluate the long-term effects of radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function. Twenty-four patients with NPC who received radiotherapy at least 12 months ago were recruited. Fourteen healthy subjects with similar demographical characteristics were recruited as the healthy control group. All volunteers were subjected to a nasoendoscopical examination, and abnormalities that could potentially cause olfactory dysfunction were the exclusion criteria from the study. An experienced radiologist segmented the MRI coronal, axial and sagittal slices manually for three-dimensional OB volume measurement in a blinded manner. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, and average score (0: worst, 7: best) was calculated as the total CCCRC olfactory score. The mean CCCRC score was 5.5 ± 1.1 for the nasopharyngeal cancer patients, whereas the mean score of healthy control group was 6.4 ± 0.4. There was a significant difference in the olfactory scores (p=0.003). The mean OB volume in the NPC group was 46.7 ± 12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8mm(3). The OB volumes of the healthy control group were significantly higher (polfactory function. Chemosensory olfactory dysfunction might be a contributing factor to lack of appetite, cancer cachexia and consequent lowered quality of life in NPC patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Sequestration within nuclear chromocenters is not a requirement for silencing olfactory receptor transcription in a placode-derived cell line.

    Science.gov (United States)

    Kilinc, Seda; Meredith, Diane T; Lane, Robert P

    2014-01-01

    Mouse olfaction depends on specialized olfactory sensory neurons (OSNs) that each express only one olfactory receptor protein from among a family of >1000 olfactory receptor (OR) genes encoded in the genome. To investigate epigenetic mechanisms underlying monogenic OR expression, we characterized the nuclear organization of OR loci in an olfactory placode-derived cell line (OP6) derived from a pre-neuronal cell along the OSN lineage. OR loci are significantly enriched within nuclear chromocenters in these cells as compared with control loci tested. However, we observe variability in chromocenter occupancy among different OR loci and from cell-to-cell, suggesting that these associations are transient or context dependent. The lamin B receptor (LBR), whose downregulation is necessary for aggregation of chromocenters and OR genes in mature OSNs, exhibits an unusual non-peripheral expression pattern in OP6 nuclei; upon further OP6 cell differentiation, LBR expression is lost and chromocenters begin to aggregate. However, neither undifferentiated nor differentiated OP6 cells sequester OR genes within the chromocenters, despite the establishment of monogenic OR expression in these cells. These results indicate that sequestration of competing OR loci is not a requirement for monogenic OR expression in OP6 cells, and could indicate that the initial establishment of monogenic OR expression during OSN differentiation in vivo occurs prior to recruitment of OR genes into chromocenters.

  5. Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.

    Science.gov (United States)

    Tong, Jia; Okutani, Fumino; Murata, Yoshihiro; Taniguchi, Mutsuo; Namba, Toshiharu; Wang, Yu-Jie; Kaba, Hideto

    2017-03-06

    Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1μM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Neural sensitivity to odorants in deprived and normal olfactory bulbs.

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    Francisco B Rodríguez

    Full Text Available Early olfactory deprivation in rodents is accompanied by an homeostatic regulation of the synaptic connectivity in the olfactory bulb (OB. However, its consequences in the neural sensitivity and discrimination have not been elucidated. We compared the odorant sensitivity and discrimination in early sensory deprived and normal OBs in anesthetized rats. We show that the deprived OB exhibits an increased sensitivity to different odorants when compared to the normal OB. Our results indicate that early olfactory stimulation enhances discriminability of the olfactory stimuli. We found that deprived olfactory bulbs adjusts the overall excitatory and inhibitory mitral cells (MCs responses to odorants but the receptive fields become wider than in the normal olfactory bulbs. Taken together, these results suggest that an early natural sensory stimulation sharpens the receptor fields resulting in a larger discrimination capability. These results are consistent with previous evidence that a varied experience with odorants modulates the OB's synaptic connections and increases MCs selectivity.

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  11. Topographical representation of odor hedonics in the olfactory bulb.

    Science.gov (United States)

    Kermen, Florence; Midroit, Maëllie; Kuczewski, Nicola; Forest, Jérémy; Thévenet, Marc; Sacquet, Joëlle; Benetollo, Claire; Richard, Marion; Didier, Anne; Mandairon, Nathalie

    2016-07-01

    Hedonic value is a dominant aspect of olfactory perception. Using optogenetic manipulation in freely behaving mice paired with immediate early gene mapping, we demonstrate that hedonic information is represented along the antero-posterior axis of the ventral olfactory bulb. Using this representation, we show that the degree of attractiveness of odors can be bidirectionally modulated by local manipulation of the olfactory bulb's neural networks in freely behaving mice.

  12. Genetic diversity of canine olfactory receptors

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    Hitte Christophe

    2009-01-01

    Full Text Available Abstract Background Evolution has resulted in large repertoires of olfactory receptor (OR genes, forming the largest gene families in mammalian genomes. Knowledge of the genetic diversity of olfactory receptors is essential if we are to understand the differences in olfactory sensory capability between individuals. Canine breeds constitute an attractive model system for such investigations. Results We sequenced 109 OR genes considered representative of the whole OR canine repertoire, which consists of more than 800 genes, in a cohort of 48 dogs of six different breeds. SNP frequency showed the overall level of polymorphism to be high. However, the distribution of SNP was highly heterogeneous among OR genes. More than 50% of OR genes were found to harbour a large number of SNP, whereas the rest were devoid of SNP or only slightly polymorphic. Heterogeneity was also observed across breeds, with 25% of the SNP breed-specific. Linkage disequilibrium within OR genes and OR clusters suggested a gene conversion process, consistent with a mean level of polymorphism higher than that observed for introns and intergenic sequences. A large proportion (47% of SNP induced amino-acid changes and the Ka/Ks ratio calculated for all alleles with a complete ORF indicated a low selective constraint with respect to the high level of redundancy of the olfactory combinatory code and an ongoing pseudogenisation process, which affects dog breeds differently. Conclusion Our demonstration of a high overall level of polymorphism, likely to modify the ligand-binding capacity of receptors distributed differently within the six breeds tested, is the first step towards understanding why Labrador Retrievers and German Shepherd Dogs have a much greater potential for use as sniffer dogs than Pekingese dogs or Greyhounds. Furthermore, the heterogeneity in OR polymorphism observed raises questions as to why, in a context in which most OR genes are highly polymorphic, a subset of

  13. Profound Olfactory Dysfunction in Myasthenia Gravis

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    Leon-Sarmiento, Fidias E.; Bayona, Edgardo A.; Bayona-Prieto, Jaime; Osman, Allen; Doty, Richard L.

    2012-01-01

    In this study we demonstrate that myasthenia gravis, an autoimmune disease strongly identified with deficient acetylcholine receptor transmission at the post-synaptic neuromuscular junction, is accompanied by a profound loss of olfactory function. Twenty-seven MG patients, 27 matched healthy controls, and 11 patients with polymiositis, a disease with peripheral neuromuscular symptoms analogous to myasthenia gravis with no known central nervous system involvement, were tested. All were administered the University of Pennsylvania Smell Identification Test (UPSIT) and the Picture Identification Test (PIT), a test analogous in content and form to the UPSIT designed to control for non-olfactory cognitive confounds. The UPSIT scores of the myasthenia gravis patients were markedly lower than those of the age- and sex-matched normal controls [respective means (SDs) = 20.15 (6.40) & 35.67 (4.95); p<0.0001], as well as those of the polymiositis patients who scored slightly below the normal range [33.30 (1.42); p<0.0001]. The latter finding, along with direct monitoring of the inhalation of the patients during testing, implies that the MG-related olfactory deficit is unlikely due to difficulties sniffing, per se. All PIT scores were within or near the normal range, although subtle deficits were apparent in both the MG and PM patients, conceivably reflecting influences of mild cognitive impairment. No relationships between performance on the UPSIT and thymectomy, time since diagnosis, type of treatment regimen, or the presence or absence of serum anti-nicotinic or muscarinic antibodies were apparent. Our findings suggest that MG influences olfactory function to the same degree as observed in a number of neurodegenerative diseases in which central nervous system cholinergic dysfunction has been documented. PMID:23082113

  14. Circadian regulation of insect olfactory learning.

    Science.gov (United States)

    Decker, Susan; McConnaughey, Shannon; Page, Terry L

    2007-10-02

    Olfactory learning in insects has been used extensively for studies on the neurobiology, genetics, and molecular biology of learning and memory. We show here that the ability of the cockroach Leucophaea maderae to acquire olfactory memories is regulated by the circadian system. We investigated the effect of training and testing at different circadian phases on performance in an odor-discrimination test administered 30 min after training (short-term memory) or 48 h after training (long-term memory). When odor preference was tested by allowing animals to choose between two odors (peppermint and vanilla), untrained cockroaches showed a clear preference for vanilla at all circadian phases, indicating that there was no circadian modulation of initial odor preference or ability to discriminate between odors. After differential conditioning, in which peppermint odor was associated with a positive unconditioned stimulus of sucrose solution and vanilla odor was associated with a negative unconditioned stimulus of saline solution, cockroaches conditioned in the early subjective night showed a strong preference for peppermint and retained the memory for at least 2 days. Animals trained and tested at other circadian phases showed significant deficits in performance for both short- and long-term memory. Performance depended on the circadian time (CT) of training, not the CT of testing, and results indicate that memory acquisition rather than retention or recall is modulated by the circadian system. The data suggest that the circadian system can have profound effects on olfactory learning in insects.

  15. Functional neuroanatomy of Drosophila olfactory memory formation.

    Science.gov (United States)

    Guven-Ozkan, Tugba; Davis, Ronald L

    2014-10-01

    New approaches, techniques and tools invented over the last decade and a half have revolutionized the functional dissection of neural circuitry underlying Drosophila learning. The new methodologies have been used aggressively by researchers attempting to answer three critical questions about olfactory memories formed with appetitive and aversive reinforcers: (1) Which neurons within the olfactory nervous system mediate the acquisition of memory? (2) What is the complete neural circuitry extending from the site(s) of acquisition to the site(s) controlling memory expression? (3) How is information processed across this circuit to consolidate early-forming, disruptable memories to stable, late memories? Much progress has been made and a few strong conclusions have emerged: (1) Acquisition occurs at multiple sites within the olfactory nervous system but is mediated predominantly by the γ mushroom body neurons. (2) The expression of long-term memory is completely dependent on the synaptic output of α/β mushroom body neurons. (3) Consolidation occurs, in part, through circuit interactions between mushroom body and dorsal paired medial neurons. Despite this progress, a complete and unified model that details the pathway from acquisition to memory expression remains elusive. © 2014 Guven-Ozkan and Davis; Published by Cold Spring Harbor Laboratory Press.

  16. Higher Body Mass Index Is Associated with Subjective Olfactory Dysfunction

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    Z. M. Patel

    2015-01-01

    Full Text Available Background. Morbidly obese patients demonstrate altered olfactory acuity. There has been no study directly assessing Body Mass Index (BMI in patients with olfactory dysfunction. Our purpose was to compare BMI in a group of patients with subjective olfactory dysfunction to those without subjective olfactory complaints. Methods. Retrospective matched case-control study. Sixty patients who presented to a tertiary care otolaryngology center with subjective smell dysfunction over one year were identified. Neoplastic and obstructive etiologies were excluded. Demographics, BMI, and smoking status were reviewed. Sixty age, gender, and race matched control patients were selected for comparison. Chi-square testing was used. Results. 48 out of 60 patients (80% in the olfactory dysfunction group fell into the overweight or obese categories, compared to 36 out of 60 patients (60% in the control group. There was a statistically significant difference between the olfactory dysfunction and control groups for this stratified BMI (p= 0.0168.  Conclusion. This study suggests high BMI is associated with olfactory dysfunction. Prospective clinical research should examine this further to determine if increasing BMI may be a risk factor in olfactory loss and to elucidate what role olfactory loss may play in diet and feeding habits of obese patients.

  17. Anatomy, histochemistry and immunohistochemistry of the olfactory subsystems in mice

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    Arthur William Barrios

    2014-07-01

    Full Text Available The four regions of the murine nasal cavity featuring olfactory neurons were studied anatomically and by labelling with lectins and relevant antibodies with a view to establishing criteria for the identification of olfactory subsystems that are readily applicable to other mammals. In the main olfactory epithelium and the septal organ the olfactory sensory neurons (OSNs are embedded in quasi-stratified columnar epithelium; vomeronasal OSNs are embedded in epithelium lining the medial interior wall of the vomeronasal duct and do not make contact with the mucosa of the main nasal cavity; and in Grüneberg’s ganglion a small isolated population of OSNs lies adjacent to, but not within, the epithelium. With the exception of Grüneberg’s ganglion, all the tissues expressing olfactory marker protein (OMP (the above four nasal territories, the vomeronasal and main olfactory nerves, and the main and accessory olfactory bulbs are also labelled by Lycopersicum esculentum agglutinin, while Ulex europaeus agglutinin I labels all and only tissues expressing Gi2 (the apical sensory neurons of the vomeronasal organ, their axons, and their glomerular destinations in the anterior accessory olfactory bulb. These staining patterns of UEA-I and LEA may facilitate the characterization of olfactory anatomy in other species. A 710-section atlas of the anatomy of the murine nasal cavity has been made available on line.

  18. The sorting behaviour of olfactory and vomeronasal axons during regeneration.

    Science.gov (United States)

    Chehrehasa, Fatemeh; St John, James; Key, Brian

    2005-09-01

    In order to begin to understand how primary olfactory and vomeronasal organ (VNO) axons target specific regions of the olfactory bulb, we examined the sorting behaviour of these axons following neonatal unilateral olfactory bulbectomy. Bulbectomy induced widespread ipsilateral death of the primary olfactory and VNO neurons. After 4 weeks, many new sensory axons had re-grown into the cranial cavity and established a prominent plexus with evidence of dense tufts that were similar in gross appearance to glomeruli. Axons expressing the cell adhesion molecule OCAM, which normally innervate the ventrolateral and rostral halves of the main and accessory olfactory bulbs, respectively, sorted out and segregated from those axons not expressing this molecule within the plexus. In addition, VNO axons formed large discrete bundles that segregated from main olfactory axons within the plexus. Thus, VNO and primary olfactory axons as well as discrete subpopulations of both are able to sort out and remain segregated in the absence of the olfactory bulb. Sorting and convergence of axons therefore occur independently of the olfactory bulb and are probably attributable either to inherent properties of the axons themselves or to interactions between the axons and accompanying glial ensheathing cells.

  19. Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism.

    Science.gov (United States)

    Salihoglu, Murat; Kurt, Onuralp; Ay, Seyid Ahmet; Baskoy, Kamil; Altundag, Aytug; Saglam, Muzaffer; Deniz, Ferhat; Tekeli, Hakan; Yonem, Arif; Hummel, Thomas

    2017-08-24

    Idiopathic hypogonadotrophic hypogonadism (IHH) with an olfactory deficit is defined as Kallmann syndrome (KS) and is distinct from normosmic IHH. Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with IHH. This case-control study included 31 controls and 45 IHH patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume (OBV) measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic IHH (aIHH), hyposmic IHH (hIHH) and normosmic IHH (nIHH). Discrimination, identification and threshold scores of patients with KS were significantly lower than controls. Threshold scores of patients with nIHH were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the aIHH group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic IHH groups and controls. OBV was lower bilaterally in all patient groups when compared with controls. The OBV of both sides was found to be significantly correlated with TDI scores in IHH patients. 1) There were no significant differences in gustatory function between controls and IHH patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the HH group. The current results indicate a continuum from anosmia to normosmia in IHH patients. Copyright © 2017

  20. Mechanisms of regulation of olfactory transduction and adaptation in the olfactory cilium.

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    Antunes, Gabriela; Sebastião, Ana Maria; Simoes de Souza, Fabio Marques

    2014-01-01

    Olfactory adaptation is a fundamental process for the functioning of the olfactory system, but the underlying mechanisms regulating its occurrence in intact olfactory sensory neurons (OSNs) are not fully understood. In this work, we have combined stochastic computational modeling and a systematic pharmacological study of different signaling pathways to investigate their impact during short-term adaptation (STA). We used odorant stimulation and electroolfactogram (EOG) recordings of the olfactory epithelium treated with pharmacological blockers to study the molecular mechanisms regulating the occurrence of adaptation in OSNs. EOG responses to paired-pulses of odorants showed that inhibition of phosphodiesterases (PDEs) and phosphatases enhanced the levels of STA in the olfactory epithelium, and this effect was mimicked by blocking vesicle exocytosis and reduced by blocking cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and vesicle endocytosis. These results suggest that G-coupled receptors (GPCRs) cycling is involved with the occurrence of STA. To gain insights on the dynamical aspects of this process, we developed a stochastic computational model. The model consists of the olfactory transduction currents mediated by the cyclic nucleotide gated (CNG) channels and calcium ion (Ca(2+))-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca(2+), and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca(2+) response, two second messengers implicated with STA occurrence. The model reproduced the experimental data for each pharmacological treatment and provided a mechanistic explanation for the action of GPCR cycling in the levels of second messengers modulating the levels of STA. All together, these experimental and theoretical results indicate the existence of a mechanism of regulation of STA by signaling pathways that control

  1. Photoperiod mediated changes in olfactory bulb neurogenesis and olfactory behavior in male white-footed mice (Peromyscus leucopus.

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    James C Walton

    Full Text Available Brain plasticity, in relation to new adult mammalian neurons generated in the subgranular zone of the hippocampus, has been well described. However, the functional outcome of new adult olfactory neurons born in the subventricular zone of the lateral ventricles is not clearly defined, as manipulating neurogenesis through various methods has given inconsistent and conflicting results in lab mice. Several small rodent species, including Peromyscus leucopus, display seasonal (photoperiodic brain plasticity in brain volume, hippocampal function, and hippocampus-dependent behaviors; plasticity in the olfactory system of photoperiodic rodents remains largely uninvestigated. We exposed adult male P. leucopus to long day lengths (LD and short day lengths (SD for 10 to 15 weeks and then examined olfactory bulb cell proliferation and survival using the thymidine analog BrdU, olfactory bulb granule cell morphology using Golgi-Cox staining, and behavioral investigation of same-sex conspecific urine. SD mice did not differ from LD counterparts in granular cell morphology of the dendrites or in dendritic spine density. Although there were no differences due to photoperiod in habituation to water odor, SD mice rapidly habituated to male urine, whereas LD mice did not. In addition, short day induced changes in olfactory behavior were associated with increased neurogenesis in the caudal plexiform and granule cell layers of the olfactory bulb, an area known to preferentially respond to water-soluble odorants. Taken together, these data demonstrate that photoperiod, without altering olfactory bulb neuronal morphology, alters olfactory bulb neurogenesis and olfactory behavior in Peromyscus leucopus.

  2. Interneurons and beta-amyloid in the olfactory bulb, anterior olfactory nucleus and olfactory tubercle in APPxPS1 transgenic mice model of Alzheimer's disease.

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    Saiz-Sanchez, Daniel; De La Rosa-Prieto, Carlos; Ubeda-Bañon, Isabel; Martinez-Marcos, Alino

    2013-09-01

    Impaired olfaction has been described as an early symptom in Alzheimer's disease (AD). Neuroanatomical changes underlying this deficit in the olfactory system are largely unknown. Given that interneuron populations are crucial in olfactory information processing, we have quantitatively analyzed somatostatin- (SOM), parvalbumin- (PV), and calretinin-expressing (CR) cells in the olfactory bulb, anterior olfactory nucleus, and olfactory tubercle in PS1 x APP double transgenic mice model of AD. The experiments were performed in wild type and double transgenic homozygous animal groups of 2, 4, 6, and 8 months of age to analyze early stages of the pathology. In addition, beta-amyloid (Aβ) expression and its correlation with SOM cells have been quantified under confocal microscopy. The results indicate increasing expressions of Aβ with aging as well as an early fall of SOM and CR expression, whereas PV was decreased later in the disease progression. These observations evidence an early, preferential vulnerability of SOM and CR cells in rostral olfactory structures during AD that may be useful to unravel neural basis of olfactory deficits associated to this neurodegenerative disorder. Copyright © 2013 Wiley Periodicals, Inc.

  3. Visualizing olfactory learning functional imaging of experience-induced olfactory bulb changes.

    Science.gov (United States)

    Fletcher, Max L; Bendahmane, Mounir

    2014-01-01

    The anatomical organization of sensory neuron input allows odor information to be transformed into odorant-specific spatial maps of mitral/tufted cell glomerular activity. In other sensory systems, neuronal representations of sensory stimuli can be reorganized or enhanced following learning or experience. Similarly, several studies have demonstrated both structural and physiological experience-induced changes throughout the olfactory system. As experience-induced changes within this circuit likely serve as an initial site for odor memory formation, the olfactory bulb is an ideal site for optical imaging studies of olfactory learning, as they allow for the visualization of experience-induced changes in the glomerular circuit following learning and how these changes impact of odor representations with the bulb. Presently, optical imaging techniques have been used to visualize experience-induced changes in glomerular odor representations in a variety of paradigms in short-term habituation, chronic odor exposure, and olfactory associative conditioning. © 2014 Elsevier B.V. All rights reserved.

  4. Olfactory aversive conditioning alters olfactory bulb mitral/tufted cell glomerular odor responses

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    Max L Fletcher

    2012-03-01

    Full Text Available The anatomical organization of receptor neuron input into the olfactory bulb (OB allows odor information to be transformed into an odorant-specific spatial map of mitral/tufted cell glomerular activity at the upper level of the olfactory bulb. In other sensory systems, neuronal representations of stimuli can be reorganized or enhanced following learning. While the mammalian OB has been shown to undergo experience-dependent plasticity at the glomerular level, it is still unclear if similar representational change occurs within mitral/tufted cell glomerular odor representations following learning. To address this, odorant-evoked glomerular activity patterns were imaged in mice expressing a GFP-based calcium indicator (GCaMP2 in OB mitral/tufted cells. Glomerular odor responses were imaged before and after olfactory associative conditioning to aversive foot shock. Following conditioning, we found no overall reorganization of the glomerular representation. Training, however, did significantly alter the amplitudes of individual glomeruli within the representation in mice in which the odor was presented together with foot shock. Further, the specific pairing of foot shock with odor presentations lead to increased responses primarily in initially weakly activated glomeruli. Overall, these results suggest that associative conditioning can enhance the initial representation of odors within the olfactory bulb by enhancing responses to the learned odor in some glomeruli.

  5. Loss of olfactory cell adhesion molecule reduces the synchrony of mitral cell activity in olfactory glomeruli.

    Science.gov (United States)

    Borisovska, Maria; McGinley, Matthew J; Bensen, AeSoon; Westbrook, Gary L

    2011-04-15

    Odours generate activity in olfactory receptor neurons, whose axons contact the dendritic tufts of mitral cells within olfactory bulb glomeruli. These axodendritic synapses are anatomically separated from dendrodendritic synapses within each glomerulus. Mitral cells within a glomerulus show highly synchronized activity as assessed with whole-cell recording from pairs of mitral cells. We examined glomerular activity in mice lacking the olfactory cell adhesion molecule (OCAM). Glomeruli in mice lacking OCAM show a redistribution of synaptic subcompartments, but the total area occupied by axonal inputs was similar to wild-type mice. Stimulation of olfactory nerve bundles showed that excitatory synaptic input to mitral cells as well as dendrodendritic inhibition was unaffected in the knockout. However, correlated spiking in mitral cells was significantly reduced, as was electrical coupling between apical dendrites. To analyse slow network dynamics we induced slow oscillations with a glutamate uptake blocker. Evoked and spontaneous slow oscillations in mitral cells and external tufted cells were broader and had multiple peaks in OCAM knockout mice, indicating that synchrony of slow glomerular activity was also reduced. To assess the degree of shared activity between mitral cells under physiological conditions, we analysed spontaneous sub-threshold voltage oscillations using coherence analysis. Coherent activity was markedly reduced in cells from OCAM knockout mice across a broad range of frequencies consistent with a decrease in tightly time-locked activity. We suggest that synchronous activity within each glomerulus is dependent on segregation of synaptic subcompartments.

  6. Anatomic olfactory structural abnormalities in congenital smell loss: magnetic resonance imaging evaluation of olfactory bulb, groove, sulcal, and hippocampal morphology.

    Science.gov (United States)

    Levy, Lucien M; Degnan, Andrew J; Sethi, Ila; Henkin, Robert I

    2013-01-01

    There are 2 groups of patients with congenital smell loss: group 1 (12% of the total), in which patients exhibit a familial smell loss in conjunction with severe anatomical, somatic, neurological, and metabolic abnormalities such as hypogonadotropic hypogonadism; and a larger group, group 2 (88% of the total), in which patients possess a similar degree of smell loss but without somatic, neurological, or anatomical abnormalities or hypogonadism. Both groups are characterized by similar olfactory dysfunction, and both have been reported to have absent or decreased olfactory bulbs and grooves, which indicates some overlap in olfactory pathophysiology and anatomy. The purpose of this study was to evaluate patients with congenital smell loss, primarily among group 2 patients, comparing brain magnetic resonance imaging (MRI) results in patients with types of hyposmia. Forty group 2 patients were studied by measurements of taste (gustometry) and smell (olfactometry) function and by use of MRI in which measurements of olfactory bulbs, olfactory sulcus depth, olfactory grooves, and hippocampal anatomy were performed. Anatomical results were compared with similar studies in group 1 patients and in 22 control subjects with normal sensory function. Olfactometry was abnormal in all patients with no patient reporting ever having normal olfaction. No patient had a familial history of smell loss. On MRI, all exhibited at least 1 abnormality in olfactory system anatomy, including absence or decreased size of at least 1 olfactory bulb, decreased depth of an olfactory sulcus, and abnormalities involving hippocampal anatomy with hippocampal malrotations. One patient had bilateral bulb duplication. Normal subjects with normal smell and taste function exhibited some but very few or significant neuroanatomical changes on MRI. Although both groups have similar abnormalities of smell function, group 2 patients demonstrate anatomical anomalies in olfactory structures that are neither as

  7. Kappe neurons, a novel population of olfactory sensory neurons

    Science.gov (United States)

    Ahuja, Gaurav; Nia, Shahrzad Bozorg; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I.

    2014-02-01

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  8. Construction of odor representations by olfactory bulb microcircuits.

    Science.gov (United States)

    Cleland, Thomas A

    2014-01-01

    Like other sensory systems, the olfactory system transduces specific features of the external environment and must construct an organized sensory representation from these highly fragmented inputs. As with these other systems, this representation is not accurate per se, but is constructed for utility, and emphasizes certain, presumably useful, features over others. I here describe the cellular and circuit mechanisms of the peripheral olfactory system that underlie this process of sensory construction, emphasizing the distinct architectures and properties of the two prominent computational layers in the olfactory bulb. Notably, while the olfactory system solves essentially similar conceptual problems to other sensory systems, such as contrast enhancement, activity normalization, and extending dynamic range, its peculiarities often require qualitatively different computational algorithms than are deployed in other sensory modalities. In particular, the olfactory modality is intrinsically high dimensional, and lacks a simple, externally defined basis analogous to wavelength or pitch on which elemental odor stimuli can be quantitatively compared. Accordingly, the quantitative similarities of the receptive fields of different odorant receptors (ORs) vary according to the statistics of the odor environment. To resolve these unusual challenges, the olfactory bulb appears to utilize unique nontopographical computations and intrinsic learning mechanisms to perform the necessary high-dimensional, similarity-dependent computations. In sum, the early olfactory system implements a coordinated set of early sensory transformations directly analogous to those in other sensory systems, but accomplishes these with unique circuit architectures adapted to the properties of the olfactory modality. © 2014 Elsevier B.V. All rights reserved.

  9. Comparison between Olfactory Function of Pregnant Women and ...

    African Journals Online (AJOL)

    2016-11-15

    Nov 15, 2016 ... Background: Pregnant women require normal olfactory function in order to develop good appetite for healthy living and normal fetal development. This study was carried out to investigate and compare olfactory function of pregnant women with non-pregnant women. Methods: This was a case control study ...

  10. Neural correlates of olfactory processing in congenital blindness

    DEFF Research Database (Denmark)

    Kupers, R; Beaulieu-Lefebvre, M; Schneider, F C

    2011-01-01

    Adaptive neuroplastic changes have been well documented in congenitally blind individuals for the processing of tactile and auditory information. By contrast, very few studies have investigated olfactory processing in the absence of vision. There is ample evidence that the olfactory system is hig...

  11. The role of main olfactory and vomeronasal systems in animal ...

    African Journals Online (AJOL)

    The great diversity of signals used in chemical communication indicates that this communication is not mediated exclusively by pheromones. A number of pheromonal responses are not dependent on the vomeronasal system, but on the main olfactory system. The dual olfactory systems also have overlappng functons.

  12. Comparison between Olfactory Function of Pregnant Women and ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... study was carried out to investigate and compare olfactory function of pregnant women with non-pregnant ... Pregnant women have olfactory dysfunction more than the non-pregnant women of reproductive age group. Also, they ..... Olfaction is linked to important cognitive and emotional domains such as the ...

  13. A second look at the structure of human olfactory memory.

    Science.gov (United States)

    White, Theresa L

    2009-07-01

    How do we remember olfactory information? Is the architecture of human olfactory memory unique compared with that of memory for other types of stimuli? Ten years ago, a review article evaluated these questions, as well as the distinction between long- and short-term olfactory memory, with three lines of evidence: capacity differences, coding differences, and neuropsychological evidence, though serial position effects were also considered. From the data available at the time, the article preliminarily suggested that olfactory memory was a two-component system that was not qualitatively different from memory systems for other types of stimuli. The decade that has elapsed since then has ushered in considerable changes in theories of memory structure and provided huge advances in neuroscience capabilities. Not only have many studies exploring various aspects of olfactory memory been published, but a model of olfactory perception that includes an integral unitary memory system also has been presented. Consequently, the structure of olfactory memory is reevaluated in the light of further information currently available with the same theoretical lines of evidence previously considered. This evaluation finds that the preponderance of evidence suggests that, as in memory for other types of sensory stimuli, the short-term-long-term distinction remains a valuable dissociation for conceptualizing olfactory memory, though perhaps not as architecturally separate systems.

  14. Voltage-Dependent Intrinsic Bursting in Olfactory Bulb Golgi Cells

    Science.gov (United States)

    Pressler, R. Todd; Rozman, Peter A.; Strowbridge, Ben W.

    2013-01-01

    In the mammalian olfactory bulb (OB), local synaptic circuits modulate the evolving pattern of activity in mitral and tufted cells following olfactory sensory stimulation. GABAergic granule cells, the most numerous interneuron subtype in this brain region, have been extensively studied. However, classic studies using Golgi staining methods…

  15. Semaphorins and their receptors in olfactory axon guidance

    NARCIS (Netherlands)

    Pasterkamp, R Jeroen; Ruitenberg, Marc J; Verhaagen, J

    The mammalian olfactory system is capable of discriminating among a large variety of odor molecules and is therefore essential for the identification of food, enemies and mating partners. The assembly and maintenance of olfactory connectivity have been shown to depend on the combinatorial actions of

  16. Comparison between olfactory function of pregnant women and non ...

    African Journals Online (AJOL)

    Background: Pregnant women require normal olfactory function in order to develop good appetite for healthy living and normal fetal development. This study was carried out to investigate and compare olfactory function of pregnant women with non-pregnant women. Methods: This was a case control study of women in ...

  17. Cell-Type-Specific Modulation of Sensory Responses in Olfactory Bulb Circuits by Serotonergic Projections from the Raphe Nuclei.

    Science.gov (United States)

    Brunert, Daniela; Tsuno, Yusuke; Rothermel, Markus; Shipley, Michael T; Wachowiak, Matt

    2016-06-22

    Serotonergic neurons in the brainstem raphe nuclei densely innervate the olfactory bulb (OB), where they can modulate the initial representation and processing of olfactory information. Serotonergic modulation of sensory responses among defined OB cell types is poorly characterized in vivo Here, we used cell-type-specific expression of optical reporters to visualize how raphe stimulation alters sensory responses in two classes of GABAergic neurons of the mouse OB glomerular layer, periglomerular (PG) and short axon (SA) cells, as well as mitral/tufted (MT) cells carrying OB output to piriform cortex. In PG and SA cells, brief (1-4 s) raphe stimulation elicited a large increase in the magnitude of responses linked to inhalation of ambient air, as well as modest increases in the magnitude of odorant-evoked responses. Near-identical effects were observed when the optical reporter of glutamatergic transmission iGluSnFR was expressed in PG and SA cells, suggesting enhanced excitatory input to these neurons. In contrast, in MT cells imaged from the dorsal OB, raphe stimulation elicited a strong increase in resting GCaMP fluorescence with only a slight enhancement of inhalation-linked responses to odorant. Finally, optogenetically stimulating raphe serotonergic afferents in the OB had heterogeneous effects on presumptive MT cells recorded extracellularly, with an overall modest increase in resting and odorant-evoked responses during serotonergic afferent stimulation. These results suggest that serotonergic afferents from raphe dynamically modulate olfactory processing through distinct effects on multiple OB targets, and may alter the degree to which OB output is shaped by inhibition during behavior. Modulation of the circuits that process sensory information can profoundly impact how information about the external world is represented and perceived. This study investigates how the serotonergic system modulates the initial processing of olfactory information by the

  18. The age of olfactory bulb neurons in humans.

    Science.gov (United States)

    Bergmann, Olaf; Liebl, Jakob; Bernard, Samuel; Alkass, Kanar; Yeung, Maggie S Y; Steier, Peter; Kutschera, Walter; Johnson, Lars; Landén, Mikael; Druid, Henrik; Spalding, Kirsty L; Frisén, Jonas

    2012-05-24

    Continuous turnover of neurons in the olfactory bulb is implicated in several key aspects of olfaction. There is a dramatic decline postnatally in the number of migratory neuroblasts en route to the olfactory bulb in humans, and it has been unclear to what extent the small number of neuroblasts at later stages contributes new neurons to the olfactory bulb. We have assessed the age of olfactory bulb neurons in humans by measuring the levels of nuclear bomb test-derived (14)C in genomic DNA. We report that (14)C concentrations correspond to the atmospheric levels at the time of birth of the individuals, establishing that there is very limited, if any, postnatal neurogenesis in the human olfactory bulb. This identifies a fundamental difference in the plasticity of the human brain compared to other mammals. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Neural circuits mediating olfactory-driven behavior in fish

    Science.gov (United States)

    Kermen, Florence; Franco, Luis M.; Wyatt, Cameron; Yaksi, Emre

    2013-01-01

    The fish olfactory system processes odor signals and mediates behaviors that are crucial for survival such as foraging, courtship, and alarm response. Although the upstream olfactory brain areas (olfactory epithelium and olfactory bulb) are well-studied, less is known about their target brain areas and the role they play in generating odor-driven behaviors. Here we review a broad range of literature on the anatomy, physiology, and behavioral output of the olfactory system and its target areas in a wide range of teleost fish. Additionally, we discuss how applying recent technological advancements to the zebrafish (Danio rerio) could help in understanding the function of these target areas. We hope to provide a framework for elucidating the neural circuit computations underlying the odor-driven behaviors in this small, transparent, and genetically amenable vertebrate. PMID:23596397

  20. Neural correlates of taste perception in congenital olfactory impairment

    DEFF Research Database (Denmark)

    Gagnon, Léa; Vestergaard, Martin; Madsen, Kristoffer

    2014-01-01

    Olfaction and gustation contribute both to the appreciation of food flavours. Although acquired loss of smell has profound consequences on the pleasure of eating, food habits and body weight, less is known about the impact of congenital olfactory impairment on gustatory processing. Here we examined...... taste identification accuracy and its neural correlates using functional magnetic resonance imaging (fMRI) in 12 congenitally olfactory impaired individuals and 8 normosmic controls. Results showed that taste identification was worse in congenitally olfactory impaired compared to control subjects. The f......MRI results demonstrated that olfactory impaired individuals had reduced activation in medial orbitofrontal cortex (mOFC) relative to normosmic subjects while tasting. In addition, olfactory performance as measured with the Sniffin׳ Sticks correlated positively with taste-induced BOLD signal increases...

  1. Understanding smell--the olfactory stimulus problem.

    Science.gov (United States)

    Auffarth, Benjamin

    2013-09-01

    The main problem with sensory processing is the difficulty in relating sensory input to physiological responses and perception. This is especially problematic at higher levels of processing, where complex cues elicit highly specific responses. In olfaction, this relationship is particularly obfuscated by the difficulty of characterizing stimulus statistics and perception. The core questions in olfaction are hence the so-called stimulus problem, which refers to the understanding of the stimulus, and the structure-activity and structure-odor relationships, which refer to the molecular basis of smell. It is widely accepted that the recognition of odorants by receptors is governed by the detection of physico-chemical properties and that the physical space is highly complex. Not surprisingly, ideas differ about how odor stimuli should be classified and about the very nature of information that the brain extracts from odors. Even though there are many measures for smell, there is none that accurately describes all aspects of it. Here, we summarize recent developments in the understanding of olfaction. We argue that an approach to olfactory function where information processing is emphasized could contribute to a high degree to our understanding of smell as a perceptual phenomenon emerging from neural computations. Further, we argue that combined analysis of the stimulus, biology, physiology, and behavior and perception can provide new insights into olfactory function. We hope that the reader can use this review as a competent guide and overview of research activities in olfactory physiology, psychophysics, computation, and psychology. We propose avenues for research, particularly in the systematic characterization of receptive fields and of perception. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. An olfactory demography of a diverse metropolitan population

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2012-10-01

    Full Text Available Abstract Background Human perception of the odour environment is highly variable. People vary both in their general olfactory acuity as well as in if and how they perceive specific odours. In recent years, it has been shown that genetic differences contribute to variability in both general olfactory acuity and the perception of specific odours. Odour perception also depends on other factors such as age and gender. Here we investigate the influence of these factors on both general olfactory acuity and on the perception of 66 structurally and perceptually different odours in a diverse subject population. Results We carried out a large human olfactory psychophysics study of 391 adult subjects in metropolitan New York City, an ethnically and culturally diverse North American metropolis. 210 of the subjects were women and the median age was 34.6 years (range 19–75. We recorded ~2,300 data points per subject to obtain a comprehensive perceptual phenotype, comprising multiple perceptual measures of 66 diverse odours. We show that general olfactory acuity correlates with gender, age, race, smoking habits, and body type. Young, female, non-smoking subjects had the highest average olfactory acuity. Deviations from normal body type in either direction were associated with decreased olfactory acuity. Beyond these factors we also show that, surprisingly, there are many odour-specific influences of race, age, and gender on olfactory perception. We show over 100 instances in which the intensity or pleasantness perception of an odour is significantly different between two demographic groups. Conclusions These data provide a comprehensive snapshot of the olfactory sense of a diverse population. Olfactory acuity in the population is most strongly influenced by age, followed by gender. We also show a large number of diverse correlations between demographic factors and the perception of individual odours that may reflect genetic differences as well as different

  3. Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

    Science.gov (United States)

    Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

    In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

  4. Multiple reversal olfactory learning in honeybees

    Directory of Open Access Journals (Sweden)

    Theo Mota

    2010-07-01

    Full Text Available In multiple reversal learning, animals trained to discriminate a reinforced from a non-reinforced stimulus are subjected to various, successive reversals of stimulus contingencies (e.g. A+ vs. B-, A- vs. B+, A+ vs. B-. This protocol is useful to determine whether or not animals learn to learn and solve successive discriminations faster (or with fewer errors with increasing reversal experience. Here we used the olfactory conditioning of proboscis extension reflex to study how honeybees Apis mellifera perform in a multiple reversal task. Our experiment contemplated four consecutive differential conditioning phases involving the same odors (A+ vs. B- to A- vs. B+ to A+ vs. B- to A- vs. B+. We show that bees in which the weight of reinforced or non-reinforced stimuli was similar mastered the multiple olfactory reversals. Bees which failed the task exhibited asymmetric responses to reinforced and non-reinforced stimuli, thus being unable to rapidly reverse stimulus contingencies. Efficient reversers did not improve their successive discriminations but rather tended to generalize their choice to both odors at the end of conditioning. As a consequence, both discrimination and reversal efficiency decreasedalong experimental phases. This result invalidates a learning-to-learn effect and indicates that bees do not only respond to the actual stimulus contingencies but rather combine these with an average of past experiences with the same stimuli.  

  5. Olfactory sex recognition investigated in Antarctic prions.

    Directory of Open Access Journals (Sweden)

    Francesco Bonadonna

    Full Text Available Chemical signals can yield information about an animal such as its identity, social status or sex. Such signals have rarely been considered in birds, but recent results have shown that chemical signals are actually used by different bird species to find food and to recognize their home and nest. This is particularly true in petrels whose olfactory anatomy is among the most developed in birds. Recently, we have demonstrated that Antarctic prions, Pachyptila desolata, are also able to recognize and follow the odour of their partner in a Y-maze.However, the experimental protocol left unclear whether this choice reflected an olfactory recognition of a particular individual (i.e. partner or a more general sex recognition mechanism. To test this second hypothesis, male and female birds' odours were presented simultaneously to 54 Antarctic prions in a Y-maze. Results showed random behaviour by the tested bird, independent of its sex or reproductive status. Present results do not support the possibility that Antarctic prions can distinguish the sex of a conspecific through its odour but indirectly support the hypothesis that they can distinguish individual odours.

  6. Doublecortin-like knockdown in the adult mouse brain : implications for neurogenesis, neuroplasticity and behaviour

    NARCIS (Netherlands)

    Saaltink, Dirk-Jan

    2014-01-01

    The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely

  7. The evaluation of olfactory function in individuals with chronic halitosis.

    Science.gov (United States)

    Altundag, Aytug; Cayonu, Melih; Kayabasoglu, Gurkan; Salihoglu, Murat; Tekeli, Hakan; Cayonu, Sibel; Akpinar, Meltem Esen; Hummel, Thomas

    2015-01-01

    Halitosis and olfactory dysfunction may disrupt an individual's quality of life remarkably. One may ask whether halitosis has effects on olfactory functions or not? Thus, the aim of this study was to evaluate the olfactory abilities of subjects with chronic halitosis evaluated using the measurements of volatile sulfur compounds. This study was carried out in 77 subjects, with a mean age of 40.1±13.3 years, ranging from 18 to 65 years. Forty-three participants were diagnosed as halitosis according to the gas chromatography results and constituted the halitosis group. Also, a control group was created from individuals without a complaint of halitosis and also who had normal values for volatile sulfur compounds. Each subject's orthonasal olfactory and retronasal olfactory functions were assessed using "Sniffin' Sticks" and retronasal olfactory testing. The results showed that odor threshold scores were lower in participants with halitosis compared with controls. Also, hyposmia was seen more common in the halitosis group than in controls. Moreover, a significant negative correlation was found between odor threshold scores and volatile sulfur compounds levels, particularly with hydrogen sulfide and dimethyl sulfide levels. The results suggest that the chronic presence of volatile sulfur compounds may have a negative effect on olfactory function. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Olfactory Pathology in Central Nervous System Demyelinating Diseases.

    Science.gov (United States)

    DeLuca, Gabriele C; Joseph, Albert; George, Jithin; Yates, Richard L; Hamard, Marie; Hofer, Monika; Esiri, Margaret M

    2015-09-01

    Olfactory dysfunction is common in multiple sclerosis (MS). Olfactory bulb and tract pathology in MS and other demyelinating diseases remain unexplored. A human autopsy cohort of pathologically confirmed cases encompassing the spectrum of demyelinating disease (MS; n = 17), neuromyelitis optica [(NMO); n = 3] and acute disseminated encephalomyelitis [(ADEM); n = 7] was compared to neuroinflammatory [herpes simplex virus encephalitis (HSE); n = 3], neurodegenerative [Alzheimer's disease (AD); n = 4] and non-neurologic (n = 8) controls. For each case, olfactory bulbs and/or tracts were stained for myelin, axons and inflammation. Inferior frontal cortex and hippocampus were stained for myelin in a subset of MS and ADEM cases. Olfactory bulb/tract demyelination was frequent in all demyelinating diseases [MS 12/17 (70.6%); ADEM 3/7 (42.9%); NMO 2/3 (66.7%)] but was absent in HSE, AD and non-neurologic controls. Inflammation was greater in the demyelinating diseases compared to non-neurologic controls. Olfactory bulb/tract axonal loss was most severe in MS where it correlated significantly with the extent of demyelination (r = 0.610, P = 0.009) and parenchymal inflammation (r = 0.681, P = 0.003). The extent of olfactory bulb/tract demyelination correlated with that found in the adjacent inferior frontal cortex but not hippocampus. We provide unequivocal evidence that olfactory bulb/tract demyelination is frequent, can occur early and is highly inflammatory, and is specific to demyelinating disease. © 2014 International Society of Neuropathology.

  9. Cellular Architecture and Functional Aspects of the Olfactory Rosette of Wallago attu (Bleeker)

    OpenAIRE

    Ghosh, Saroj Kumar; Chakrabarti, Padmanabha

    2009-01-01

    The olfactory epithelium of Wallago attu has been studied with conventional histological techniques. The elongated olfactory rosette consists of 62 to 64 primary lamellae in each left and right rosette. The olfactory lamellae are arranged in two rows on either side of the long raphe. Each olfactory lamella consists of two layers of epithelium separated by central core. The olfactory epithelium in one side consists of mixed sensory and non-sensory epithelium while the other side is consists of...

  10. Distinct amyloid precursor protein processing machineries of the olfactory system.

    Science.gov (United States)

    Kim, Jae Yeon; Rasheed, Ameer; Yoo, Seung-Jun; Kim, So Yeun; Cho, Bongki; Son, Gowoon; Yu, Seong-Woon; Chang, Keun-A; Suh, Yoo-Hun; Moon, Cheil

    2018-01-01

    Processing of amyloid precursor protein (APP) occurs through sequential cleavages first by β-secretase and then by the γ-secretase complex. However, abnormal processing of APP leads to excessive production of β-amyloid (Aβ) in the central nervous system (CNS), an event which is regarded as a primary cause of Alzheimer's disease (AD). In particular, gene mutations of the γ-secretase complex-which contains presenilin 1 or 2 as the catalytic core-could trigger marked Aβ accumulation. Olfactory dysfunction usually occurs before the onset of typical AD-related symptoms (eg, memory loss or muscle retardation), suggesting that the olfactory system may be one of the most vulnerable regions to AD. To date however, little is known about why the olfactory system is affected so early by AD prior to other regions. Thus, we examined the distribution of secretases and levels of APP processing in the olfactory system under either healthy or pathological conditions. Here, we show that the olfactory system has distinct APP processing machineries. In particular, we identified higher expressions levels and activity of γ-secretase in the olfactory epithelium (OE) than other regions of the brain. Moreover, APP c-terminal fragments (CTF) are markedly detected. During AD progression, we note increased expression of presenilin2 of γ-secretases in the OE, not in the OB, and show that neurotoxic Aβ*56 accumulates more quickly in the OE. Taken together, these results suggest that the olfactory system has distinct APP processing machineries under healthy and pathological conditions. This finding may provide a crucial understanding of the unique APP-processing mechanisms in the olfactory system, and further highlights the correlation between olfactory deficits and AD symptoms. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Neurobiology of mammalian olfactory learning that occurs during sensitive periods

    Directory of Open Access Journals (Sweden)

    Hideto KABA

    2010-12-01

    Full Text Available This review examines the organizational principles underlying olfactory learning in three specialized contexts that occur during sensitive periods of enhanced neural plasticity and emphasizes some of their common features. All three forms of olfactory learning are associated with neural changes in the olfactory bulb (OB at the first stage of sensory processing. These changes require the association of the olfactory and somatosensory signals in the OB. They all depend on somatosensory stimulation-induced release of noradrenaline that induces structural and functional changes at mitral-granule cell reciprocal synapses in the OB, resulting in increases in inhibitory transmission. In the accessory olfactory bulb, this represents the enhanced self-inhibition of mitral cells, which selectively disrupts the transmission of the mating male’s pregnancy-blocking signal at this level. In contrast, an extensive network of secondary dendrites of mitral cells in the main olfactory bulb probably results in a sharpening of the odor-induced pattern of activity, due to increases in lateral inhibition, leading to offspring recognition in sheep and neonatal learning in rats and rabbits. These findings show that inhibitory interneurons play a critical role in olfactory learning. Further work on how these neurons shape olfactory circuit function could provide important clues to understand memory functions of interneurons in other systems. Moreover, recent research has suggested that three forms of olfactory learning are controlled by synergistic, redundant, and distributed neural mechanisms. This has general implications regarding the mechanisms that may contribute to the robustness of memories [Current Zoology 56 (6: 819–833, 2010].

  12. Face detection for interactive tabletop viewscreen system using olfactory display

    Science.gov (United States)

    Sakamoto, Kunio; Kanazawa, Fumihiro

    2009-10-01

    An olfactory display is a device that delivers smells to the nose. It provides us with special effects, for example to emit smell as if you were there or to give a trigger for reminding us of memories. The authors have developed a tabletop display system connected with the olfactory display. For delivering a flavor to user's nose, the system needs to recognition and measure positions of user's face and nose. In this paper, the authors describe an olfactory display which enables to detect the nose position for an effective delivery.

  13. Intranasal administration of rotenone in mice attenuated olfactory functions through the lesion of dopaminergic neurons in the olfactory bulb.

    Science.gov (United States)

    Sasajima, Hitoshi; Miyazono, Sadaharu; Noguchi, Tomohiro; Kashiwayanagi, Makoto

    2015-12-01

    Many environmental chemicals are thought to affect brain function. It was reported that chemicals in the nasal cavity directly reach the brain through the connection between olfactory neurons and the olfactory bulb (OB). In this 'olfactory transport,' xenobiotics absorbed at the nasal mucosa reach the brain by bypassing some physical barriers and defenses, and thus olfactory transport is suspected to be a vulnerable mechanism of the brain against invasion threats of environmental chemicals. In this study, we focused on the neuronal toxicity of rotenone administered intranasally to mice. The results showed that the mice that were administered rotenone had attenuated olfactory functions. We also found that intranasally administered rotenone induced acute mitochondrial stress at the OB. The repeated administration of rotenone resulted in a decrease in the number of dopaminergic neurons, which are inhibitory interneurons in the OB. Taken together, our findings suggest that the inhalation of environmental toxins induces the neurodegeneration of cranial neurons through olfactory transport, and that olfactory dysfunction may be induced as an earliest symptom of neurodegeneration caused by inhaled neurotoxins. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

    Science.gov (United States)

    Braun, J J; Noblet, V; Kremer, S; Molière, S; Dollfus, H; Marion, V; Goetz, N; Muller, J; Riehm, S

    2016-07-01

    Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction. The OB was evaluated separately and blindly by two radiologists (SR and SM) with 3 Tesla MRI imaging comparatively to 12 normal control subjects by global visual evaluation and by quantitative measurement of OB volume. In the 12 control cases OB visual evaluation was considered as normal in all cases for radiologist (SR) and in 10 cases for radiologist (SM). In the 20 BBS patients, OB visual evaluation was considered as abnormal in 18 cases for SR and in all cases for SM. OB volumetric evaluation for SR and SM in BBS patients was able to provide significant correlation between BBS and olfactory dysfunction. This study indicates that OB volume evaluation by MRI imaging like structural MRI scan for gray matter modifications demonstrates that olfactory dysfunction in BBS patients is a constant and cardinal symptom integrated in a genetical syndrome with peripheral and central olfactory structure alterations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Expression of polysialyltransferases (STX and PST) in adult rat olfactory bulb after an olfactory associative discrimination task.

    Science.gov (United States)

    Mione, J; Manrique, C; Duhoo, Y; Roman, F S; Guiraudie-Capraz, G

    2016-04-01

    Neuronal plasticity and neurogenesis occur in the adult hippocampus and in other brain structures such as the olfactory bulb and often involve the neural cell adhesion molecule NCAM. During an olfactory associative discrimination learning task, NCAM polysialylation triggers neuronal plasticity in the adult hippocampus. The PST enzyme likely modulates this polysialylation, but not STX, a second sialyltransferase. How the two polysialyltransferases are involved in the adult olfactory bulb remains unknown. We addressed this question by investigating the effect of olfactory associative learning on plasticity and neurogenesis. After a hippocampo-dependent olfactory associative task learning, we measured the expression of both PST and STX polysialyltransferases in the olfactory bulbs of adult rats using quantitative PCR. In parallel, immunohistochemistry was used to evaluate both NCAM polysialylation level and newly-born cells, with or without learning. After learning, no changes were observed neither in the expression level of PST and NCAM polysialylation, nor in STX gene expression level and newly-born cells number in the olfactory bulb. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Upregulation of barrel GABAergic neurons is associated with cross-modal plasticity in olfactory deficit.

    Directory of Open Access Journals (Sweden)

    Hong Ni

    Full Text Available BACKGROUND: Loss of a sensory function is often followed by the hypersensitivity of other modalities in mammals, which secures them well-awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain to be documented. METHODOLOGY/PRINCIPAL FINDINGS: Multidisciplinary approaches, such as electrophysiology, behavioral task and immunohistochemistry, were used to examine the involvement of specific types of neurons in cross-modal plasticity. We have established a mouse model that olfactory deficit leads to a whisking upregulation, and studied how GABAergic neurons are involved in this cross-modal plasticity. In the meantime of inducing whisker tactile hypersensitivity, the olfactory injury recruits more GABAergic neurons and their fine processes in the barrel cortex, as well as upregulates their capacity of encoding action potentials. The hyperpolarization driven by inhibitory inputs strengthens the encoding ability of their target cells. CONCLUSION/SIGNIFICANCE: The upregulation of GABAergic neurons and the functional enhancement of neuronal networks may play an important role in cross-modal sensory plasticity. This finding provides the clues for developing therapeutic approaches to help sensory recovery and substitution.

  17. Chromosomal localization and genomic organization of genes encoding guanylyl cyclase receptors expressed in olfactory sensory neurons and retina

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ruey-Bing; Fuelle, H.J.; Garbers, D.L. [Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

    1996-02-01

    We recently cloned three membrane guanylyl cyclases, designated GC-D, CG-E, and GC-F, from rat olfactory tissue and eye. Amino acid sequence homology suggests that they may compose a new gene subfamily of guanylyl cyclase receptors specifically expressed in sensory tissues. Their chromosomal localization was determined by mouse interspecific backcross analysis. The GC-D, CG-E, and GC-F genes (Gucy2d, Gucy2e, and Gucy2f) are dispersed through the mouse genome in that they map to chromosomes 7, 11, and X, respectively. Close proximity of the mouse GC-D gene to Omp (olfactory marker protein) and Hbb (hemoglobin {beta}-chain complex) suggests that the human homolog gene maps to 11p15.4 or 11q13.4-q14.1. The human GC-F gene was localized to the long arm of chromosome Xq22 by fluorescence in situ hybridization. The genomic organization of the mouse GC-E, and GC-F genomic clones contain identical exon-intron boundaries within their extracellular and cytoplasmic domains, demonstrating the conservation of the gene structures. With respect to human genetic diseases, GC-E mapped to mouse chromosome 11 within a syntenic region on human chromosome 17p13 that has been linked with loci for autosomal dominant retinitis pigmentosa and Leber congenital amaurosis. No apparent disease loci have been yet linked to the locations of the GC-D or GC-F genes. 39 refs., 3 figs., 2 tabs.

  18. Development of a mouse test for repetitive, restricted behaviors: relevance to autism.

    Science.gov (United States)

    Moy, Sheryl S; Nadler, Jessica J; Poe, Michele D; Nonneman, Randal J; Young, Nancy B; Koller, Beverly H; Crawley, Jacqueline N; Duncan, Gary E; Bodfish, James W

    2008-03-17

    Repetitive behavior, a core symptom of autism, encompasses stereotyped responses, restricted interests, and resistance to change. These studies investigated whether different components of the repetitive behavior domain could be modeled in the exploratory hole-board task in mice. Four inbred mouse strains, C57BL/6J, BALB/cByJ, BTBR T+tf/J, and FVB/NJ, and mice with reduced expression of Grin1, leading to NMDA receptor hypofunction (NR1neo/neo mice), were tested for exploration and preference for olfactory stimuli in an activity chamber with a 16-hole floor-board. Reduced exploration and high preference for holes located in the corners of the chamber were observed in BALB/cByJ and BTBR T+tf/J mice. All inbred strains had initial high preference for a familiar olfactory stimulus (clean cage bedding). BTBR T+tf/J was the only strain that did not demonstrate a shift in hole preference towards an appetitive olfactory stimulus (cereal or a chocolate chip), following home cage exposure to the food. The NR1neo/neo mice showed lower hole selectivity and aberrant olfactory stimulus preference, in comparison to wildtype controls. The results indicate that NR1neo/neo mice have repetitive nose poke responses that are less modified by environmental contingencies than responses in wildtype mice. 25-30% of NMDA receptor hypomorphic mice also show self-injurious responses. Findings from the olfactory studies suggest that resistance to change and restricted interests might be modeled in mice by a failure to alter patterns of hole preference following familiarization with an appetitive stimulus, and by high preference persistently demonstrated for one particular olfactory stimulus. Further work is required to determine the characteristics of optimal mouse social stimuli in the olfactory hole-board test.

  19. OCAM reveals segregated mitral/tufted cell pathways in developing accessory olfactory bulb.

    Science.gov (United States)

    von Campenhausen, H; Yoshihara, Y; Mori, K

    1997-07-28

    Two functional subsets of vomeronasal sensory neurons project their axons to two segregated zones in the accessory olfactory bulb (AOB). Using immunohistochemical methods with antibodies against the novel cell adhesion molecule OCAM, we provide evidence that the segregation of functional pathways is maintained at the level of mitral/tufted (M/T) cells of the mouse AOB and that this pattern emerges early in ontogeny. During embryonic and postnatal development OCAM was strongly expressed by M/T cells in the caudal zone of the AOB where OCAM-negative vomeronasal axons terminated. In contrast, rostral zone M/T cells innervated by OCAM-positive vomeronasal axons displayed no or faint OCAM immunoreactivity. Differential expression of OCAM in segregated M/T cell pathways suggests that OCAM may be involved in defining compartments of connectivity and setting up functional subdivisions in the developing AOB.

  20. A specialized odor memory buffer in primary olfactory cortex.

    Science.gov (United States)

    Zelano, Christina; Montag, Jessica; Khan, Rehan; Sobel, Noam

    2009-01-01

    The neural substrates of olfactory working memory are unknown. We addressed the questions of whether olfactory working memory involves a verbal representation of the odor, or a sensory image of the odor, or both, and the location of the neural substrates of these processes. We used functional magnetic resonance imaging to measure activity in the brains of subjects who were remembering either nameable or unnameable odorants. We found a double dissociation whereby remembering nameable odorants was reflected in sustained activity in prefrontal language areas, and remembering unnameable odorants was reflected in sustained activity in primary olfactory cortex. These findings suggest a novel dedicated mechanism in primary olfactory cortex, where odor information is maintained in temporary storage to subserve ongoing tasks.

  1. Olfactory and gustatory functions in bipolar disorders: A systematic review.

    Science.gov (United States)

    Kazour, Francois; Richa, Sami; Desmidt, Thomas; Lemaire, Mathieu; Atanasova, Boriana; El Hage, Wissam

    2017-05-12

    Olfactory and gustatory dysfunctions have been described in different psychiatric disorders. Several studies have found gustatory and olfactory function change in bipolar disorders with various results. The aim of this study is to have a systematic review of studies evaluating gustatory and olfactory function in bipolar disorders. After a systematic search, 15 studies on olfaction and 5 studies on taste were included in this review. The UPSIT (University of Pennsylvania Smell Identification Test) and Sniffin' Sticks were the most widely used tests to evaluate smell. Some studies on olfaction described dysfunctions in smell identification as potential markers for bipolar disorders. Moreover, olfactory acuity was associated with psychosocial and cognitive performances. For taste, only few studies used standardized tests to evaluate gustation. These studies showed that patients with Bipolar disorders had more gustatory dysfunction compared to controls, and to non-bipolar depressed patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. AASERT: Hydrodynamic Interaction Between Olfactory Antennae and Odor Plumes

    National Research Council Canada - National Science Library

    Koehl, M

    2002-01-01

    We trained graduate and undergraduate students by involving them in research elucidating ways in which the structure and the motions of olfactory antennae affect how they encounter the concentration...

  3. Calcium Signaling in Mitral Cell Dendrites of Olfactory Bulbs of Neonatal Rats and Mice during Olfactory Nerve Stimulation and Beta-Adrenoceptor Activation

    Science.gov (United States)

    Yuan, Qi; Mutoh, Hiroki; Debarbieux, Franck; Knopfel, Thomas

    2004-01-01

    Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. Beta-adrenergic modulation of electrical…

  4. Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium.

    Science.gov (United States)

    Joiner, Ariell M; Green, Warren W; McIntyre, Jeremy C; Allen, Benjamin L; Schwob, James E; Martens, Jeffrey R

    2015-10-07

    The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specific Ift88 knock-out mouse line (K5rtTA;tetOCre;Ift88(fl/fl)) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. We show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory neurons and may

  5. Telomere shortening impairs regeneration of the olfactory epithelium in response to injury but not under homeostatic conditions.

    Directory of Open Access Journals (Sweden)

    Masami Watabe-Rudolph

    Full Text Available Atrophy of the olfactory epithelium (OE associated with impaired olfaction and dry nose represents one of the most common phenotypes of human aging. Impairment in regeneration of a functional olfactory epithelium can also occur in response to injury due to infection or nasal surgery. These complications occur more frequently in aged patients. Although age is the most unifying risk factor for atrophic changes and functional decline of the olfactory epithelium, little is known about molecular mechanisms that could influence maintenance and repair of the olfactory epithelium. Here, we analyzed the influence of telomere shortening (a basic mechanism of cellular aging on homeostasis and regenerative reserve in response to chemical induced injury of the OE in late generation telomere knockout mice (G3 mTerc(-/- with short telomeres compared to wild type mice (mTerc(+/+ with long telomeres. The study revealed no significant influence of telomere shortening on homeostatic maintenance of the OE during mouse aging. In contrast, the regenerative response to chemical induced injury of the OE was significantly impaired in G3 mTerc(-/- mice compared to mTerc(+/+ mice. Seven days after chemical induced damage, G3 mTerc(-/- mice exhibited significantly enlarged areas of persisting atrophy compared to mTerc(+/+ mice (p = 0.031. Telomere dysfunction was associated with impairments in cell proliferation in the regenerating epithelium. Deletion of the cell cycle inhibitor, Cdkn1a (p21 rescued defects in OE regeneration in telomere dysfunctional mice. Together, these data indicate that telomere shortening impairs the regenerative capacity of the OE by impairing cell cycle progression in a p21-dependent manner. These findings could be relevant for the impairment in OE function in elderly people.

  6. Integrating temperature with odor processing in the olfactory bulb.

    Science.gov (United States)

    Kludt, Eugen; Okom, Camille; Brinkmann, Alexander; Schild, Detlev

    2015-05-20

    Temperature perception has long been classified as a somesthetic function solely. However, in recent years several studies brought evidence that temperature perception also takes place in the olfactory system of rodents. Temperature has been described as an effective stimulus for sensory neurons of the Grueneberg ganglion located at the entrance of the nose. Here, we investigate whether a neuronal trace of temperature stimulation can be observed in the glomeruli and mitral cells of the olfactory bulb, using calcium imaging and fast line-scanning microscopy. We show in the Xenopus tadpole system that the γ-glomerulus, which receives input from olfactory neurons, is highly sensitive to temperature drops at the olfactory epithelium. We observed that thermo-induced activity in the γ-glomerulus is conveyed to the mitral cells innervating this specific neuropil. Surprisingly, a substantial number of thermosensitive mitral cells were also chemosensitive. Moreover, we report another unique feature of the γ-glomerulus: it receives ipsilateral and contralateral afferents. The latter fibers pass through the contralateral bulb, cross the anterior commissure, and then run to the ipsilateral olfactory bulb, where they target the γ-glomerulus. Temperature drops at the contralateral olfactory epithelium also induced responses in the γ-glomerulus and in mitral cells. Temperature thus appears to be a relevant physiological input to the Xenopus olfactory system. Each olfactory bulb integrates and codes temperature signals originating from receptor neurons of the ipsilateral and contralateral nasal cavities. Finally, temperature and chemical information is processed in shared cellular networks. Copyright © 2015 the authors 0270-6474/15/357892-11$15.00/0.

  7. Parasite and predator risk assessment: nuanced use of olfactory cues

    OpenAIRE

    Sharp, John G.; Garnick, Sarah; Mark A Elgar; Coulson, Graeme

    2015-01-01

    Foraging herbivores face twin threats of predation and parasite infection, but the risk of predation has received much more attention. We evaluated, experimentally, the role of olfactory cues in predator and parasite risk assessment on the foraging behaviour of a population of marked, free-ranging, red-necked wallabies (Macropus rufogriseus). The wallabies adjusted their behaviour according to these olfactory cues. They foraged less, were more vigilant and spent less time at feeders placed in...

  8. Spotlight on olfactory dysfunction in Parkinson's disease

    OpenAIRE

    Rodríguez-Violante,Mayela; Ospina-García,Natalia; Pérez-Lohman,Christian; Cervantes-Arriaga,Amin

    2017-01-01

    Mayela Rodríguez-Violante,1,2 Natalia Ospina-García,1,2 Christian Pérez-Lohman,1,2 Amin Cervantes-Arriaga1,2 1Movement Disorders Clinic, National Institute of Neurology and Neurosurgery, Mexico City, Mexico; 2Clinical Neurodegenerative Research Unit, National Institute of Neurology and Neurosurgery, Mexico City, Mexico Abstract: Olfactory dysfunction is frequent in Parkinson’s disease (PD). A correlation between olfactory dysfunction and the pathophy...

  9. Modeling of Spatial and Temporal Dynamics in Biological Olfactory Systems

    Science.gov (United States)

    2007-09-21

    34 Neuron, 2001. 1371 B. Quenet, D. Horn, G. Dreyfus , and R. Dubois, "Temporal coding in an olfactory oscillatory model," Neurocomputing, vol. 38-40, pp...in Engineering (ANNIE 2004) Conference, St. Louis , Missouri, November 7-10, 2004, pp.791-799 Progress Report Zurada JM, Lozowskl AG, Modeling of...Engineering (ANNIE 2004) Conference, St. Louis , Missouri, November 7-10, 2004, pp.791- 799 SIMULATION OF PULSE DISTRIBUTION OBSERVED IN OLFACTORY BULB

  10. State and trait olfactory markers of major depression.

    Directory of Open Access Journals (Sweden)

    Marine Naudin

    Full Text Available Nowadays, depression is a major issue in public health. Because of the partial overlap between the brain structures involved in depression, olfaction and emotion, the study of olfactory function could be a relevant way to find specific cognitive markers of depression. This study aims at determining whether the olfactory impairments are state or trait markers of major depressive episode (MDE through the study of the olfactory parameters involving the central olfactory pathway. In a pilot study, we evaluated prospectively 18 depressed patients during acute episodes of depression and 6 weeks after antidepressant treatment (escitalopram against 54 healthy volunteers, matched by age, gender and smoking status. We investigated the participants' abilities to identify odors (single odors and in binary mixture, to evaluate and discriminate the odors' intensity, and determine the hedonic valence of odors. The results revealed an "olfactory anhedonia" expressed by decrease of hedonic score for high emotional odorant as potential state marker of MDE. Moreover, these patients experienced an "olfactory negative alliesthesia", during the odor intensity evaluation, and failed to identify correctly two odorants with opposite valences in a binary iso-mixture, which constitute potential trait markers of the disease. This study provides preliminary evidence for olfactory impairments associated with MDE (state marker that are persistent after the clinical improvement of depressive symptoms (trait marker. These results could be explained by the chronicity of depression and/or by the impact of therapeutic means used (antidepressant treatment. They need to be confirmed particularly the ones obtained in complex olfactory environment which corresponds a more objective daily life situation.

  11. Reference values of olfactory function for Mexico City inhabitants.

    Science.gov (United States)

    Guarneros, Marco; Hudson, Robyn; López-Palacios, Martha; Drucker-Colín, René

    2015-01-01

    Olfactory testing is useful in the differential diagnosis of age-related pathologies. To provide baseline reference values for clinical use in Mexico City we investigated the relation between olfactory capabilities and the principal population parameters of age, sex, and smoking habits in a large sample of healthy inhabitants. We applied the internationally recognized and commercially available Sniffin' Sticks test battery to 916 men and women from across the adult life span. The Sniffin' Sticks test evaluates three key aspects of olfactory function: 1) ability to detect an odor, 2) to discriminate between odors, and 3) to identify odors. We found a significant decline in olfactory function from the 5th decade of age, and that detection threshold was the most sensitive measure of this. We did not find a significant difference between men and women or between smokers and non-smokers. In confirmation of our previous studies of the negative effect of air pollution on olfactory function, Mexico City inhabitants had poorer overall performance than corresponding subjects previously tested in the neighboring but less polluted Mexican state of Tlaxcala. Although we basically confirm findings on general demographic patterns of olfactory performance from other countries, we also demonstrate the need to take into account local cultural, environmental and demographic factors in the clinical evaluation of olfactory performance of Mexico City inhabitants. The Sniffin' Sticks test battery, with some adjustment of stimuli to correspond to Mexican culture, provides an easily administered means of assessing olfactory health. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  12. State and trait olfactory markers of major depression.

    Science.gov (United States)

    Naudin, Marine; El-Hage, Wissam; Gomes, Marlène; Gaillard, Philippe; Belzung, Catherine; Atanasova, Boriana

    2012-01-01

    Nowadays, depression is a major issue in public health. Because of the partial overlap between the brain structures involved in depression, olfaction and emotion, the study of olfactory function could be a relevant way to find specific cognitive markers of depression. This study aims at determining whether the olfactory impairments are state or trait markers of major depressive episode (MDE) through the study of the olfactory parameters involving the central olfactory pathway. In a pilot study, we evaluated prospectively 18 depressed patients during acute episodes of depression and 6 weeks after antidepressant treatment (escitalopram) against 54 healthy volunteers, matched by age, gender and smoking status. We investigated the participants' abilities to identify odors (single odors and in binary mixture), to evaluate and discriminate the odors' intensity, and determine the hedonic valence of odors. The results revealed an "olfactory anhedonia" expressed by decrease of hedonic score for high emotional odorant as potential state marker of MDE. Moreover, these patients experienced an "olfactory negative alliesthesia", during the odor intensity evaluation, and failed to identify correctly two odorants with opposite valences in a binary iso-mixture, which constitute potential trait markers of the disease. This study provides preliminary evidence for olfactory impairments associated with MDE (state marker) that are persistent after the clinical improvement of depressive symptoms (trait marker). These results could be explained by the chronicity of depression and/or by the impact of therapeutic means used (antidepressant treatment). They need to be confirmed particularly the ones obtained in complex olfactory environment which corresponds a more objective daily life situation.

  13. The fate of the inner nose: odor imagery in patients with olfactory loss.

    Science.gov (United States)

    Flohr, E L R; Arshamian, A; Wieser, M J; Hummel, C; Larsson, M; Mühlberger, A; Hummel, T

    2014-05-30

    Cerebral activations during olfactory mental imagery are fairly well investigated in healthy participants but little attention has been given to olfactory imagery in patients with olfactory loss. To explore whether olfactory loss leads to deficits in olfactory imagery, neural responses using functional magnetic resonance imaging (fMRI) and self-report measures were investigated in 16 participants with acquired olfactory loss and 19 control participants. Participants imagined both pleasant and unpleasant odors and their visual representations. Patients reported less vivid olfactory but not visual images than controls. Results from neuroimaging revealed that activation patterns differed between patients and controls. While the control group showed stronger activation in olfactory brain regions for unpleasant compared to pleasant odors, the patient group did not. Also, activation in critical areas for olfactory imagery was correlated with the duration of olfactory dysfunction, indicating that the longer the duration of dysfunction, the more the attentional resources were employed. This indicates that participants with olfactory loss have difficulties to perform olfactory imagery in the conventional way. Regular exposure to olfactory information may be necessary to maintain an olfactory imagery capacity. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. The sea lamprey has a primordial accessory olfactory system

    Science.gov (United States)

    2013-01-01

    Background A dual olfactory system, represented by two anatomically distinct but spatially proximate chemosensory epithelia that project to separate areas of the forebrain, is known in several classes of tetrapods. Lungfish are the earliest evolving vertebrates known to have this dual system, comprising a main olfactory and a vomeronasal system (VNO). Lampreys, a group of jawless vertebrates, have a single nasal capsule containing two anatomically distinct epithelia, the main (MOE) and the accessory olfactory epithelia (AOE). We speculated that lamprey AOE projects to specific telencephalic regions as a precursor to the tetrapod vomeronasal system. Results To test this hypothesis, we characterized the neural circuits and molecular profiles of the accessory olfactory epithelium in the sea lamprey (Petromyzon marinus). Neural tract-tracing revealed direct and reciprocal connections with the dorsomedial telencephalic neuropil (DTN) which in turn projects directly to the dorsal pallium and the rostral hypothalamus. High-throughput sequencing demonstrated that the main and the accessory olfactory epithelia have virtually identical profiles of expressed genes. Real time quantitative PCR confirmed expression of representatives of all 3 chemoreceptor gene families identified in the sea lamprey genome. Conclusion Anatomical and molecular evidence shows that the sea lamprey has a primordial accessory olfactory system that may serve a chemosensory function. PMID:23957559

  15. Recency and suffix effects with immediate recall of olfactory stimuli.

    Science.gov (United States)

    Miles, C; Jenkins, R

    2000-05-01

    In contrast to our understanding of the immediate recall of auditory and visual material, little is known about the corresponding characteristics of short-term olfactory memory. The current study investigated the pattern of immediate serial recall and the associated suffix effect using olfactory stimuli. Subjects were trained initially to identify and name correctly nine different odours. Experiment 1 established an immediate correct recall span of approximately six items. In Experiment 2 participants recalled serially span equivalent lists which were followed by a visual, auditory, or olfactory suffix. Primacy was evident in the recall curves for all three suffix conditions. Recency, in contrast, was evident in the auditory and visual suffix conditions only; there was a strong suffix effect in the olfactory suffix condition. Experiment 3 replicated this pattern of effects using seven-item lists, and demonstrated that the magnitude of the recency and suffix effects obtained in the olfactory modality can equate to that obtained in the auditory modality. It is concluded that the pattern of recency and suffix effects in the olfactory modality is reliable, and poses difficulties for those theories that rely on the presence of a primary linguistic code, sound, or changing state as determinants of these effects in serial recall.

  16. Gustatory and olfactory responses to stimulation of the human insula.

    Science.gov (United States)

    Mazzola, Laure; Royet, Jean-Pierre; Catenoix, Hélène; Montavont, Alexandra; Isnard, Jean; Mauguière, François

    2017-09-01

    Despite numerous studies suggesting the role of insular cortex in the processing of gustatory and olfactory inputs, the exact location of olfactogustatory representation in the insula remains controversial. Here we provide a functional mapping of olfactory-gustatory responses to stimulation of the human insular cortex. We reviewed 651 electrical stimulations of the insula that were performed in 221 patients, using stereotactically implanted depth electrodes, during the presurgical evaluation of drug-refractory epilepsy. Gustatory sensations were evoked in 15 (2.7%) of the 550 stimulations that elicited a clinical response. They were exclusively obtained after stimulation of a relatively delimited zone of insula, located in its mid-dorsal part (posterior short gyrus). Six olfactory sensations (1.1%) could be obtained during stimulations of an insular region that partially overlapped with the gustatory representation. Our study provides a functional mapping of gustatory representation in the insular posterior short gyrus and the first detailed description of olfactory sensations obtained by direct stimulation of mid-dorsal insula. Our data also show a spatial overlap between gustatory, olfactory, and oral somatosensory representation in the mid-dorsal insula, and suggest that this part of the insula may be an integrated oral sensory region that plays a key role in flavor perception. It also indicates that dysfunction in this region should be considered during the evaluation of gustatory and olfactory epileptic seizures. Ann Neurol 2017;82:360-370. © 2017 American Neurological Association.

  17. Olfactory hallucinations elicited by electrical stimulation via subdural electrodes: effects of direct stimulation of olfactory bulb and tract.

    Science.gov (United States)

    Kumar, Gogi; Juhász, Csaba; Sood, Sandeep; Asano, Eishi

    2012-06-01

    In 1954, Penfield and Jasper briefly described that percepts of unpleasant odor were elicited by intraoperative electrical stimulation of the olfactory bulb in patients with epilepsy. Since then, few peer-reviewed studies have reported such phenomena elicited by stimulation mapping via subdural electrodes implanted on the ventral surface of the frontal lobe. Here, we determined what types of olfactory hallucinations could be reproduced by such stimulation in children with focal epilepsy. This study included 16 children (age range: 5 to 17 years) who underwent implantation of subdural electrodes to localize the presumed epileptogenic zone and eloquent areas. Pairs of electrodes were electrically stimulated, and clinical responses were observed. In case a patient reported a perception, she/he was asked to describe its nature. We also described the stimulus parameters to elicit a given symptom. Eleven patients reported a perception of smell in response to electrical stimulation while the remaining five did not. Nine patients perceived an unpleasant smell (like bitterness, smoke, or garbage) while two perceived a pleasant smell (like strawberry or good food). Such olfactory hallucinations were induced by stimulation proximal to the olfactory bulb or tract on either hemisphere but not by that of orbitofrontal gyri lateral to the medial orbital sulci. The range of stimulus parameters employed to elicit olfactory hallucinations was comparable to those for other sensorimotor symptoms. Our systematic study of children with epilepsy replicated stimulation-induced olfactory hallucinations. We failed to provide evidence that a positive olfactory perception could be elicited by conventional stimulation of secondary olfactory cortex alone. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Inverse expression of olfactory cell adhesion molecule in a subset of olfactory axons and a subset of mitral/tufted cells in the developing rat main olfactory bulb.

    Science.gov (United States)

    Treloar, Helen B; Gabeau, Darlene; Yoshihara, Yoshihiro; Mori, Kensaku; Greer, Charles A

    2003-04-14

    The projection of olfactory sensory neuron (OSN) axons from the olfactory epithelium (OE) to the olfactory bulb (OB) is highly organized but topographically complex. Evidence suggests that odorant receptor expression zones in the OE map to the OB about orthogonal axes. One candidate molecule for the formation of zone-specific targeting of OSN axon synapses onto the OB is the olfactory cell adhesion molecule (OCAM). OCAM(+) OSNs are restricted to three of the four zones in the OE and project their axons to the ventral OB where they form synapses with mitral/tufted (M/T) cells. To determine when this zonal connection is established, we have examined OCAM expression in rat olfactory system, during seminal periods of glomerular formation. OCAM(+) axons sort out in the ventral olfactory nerve layer of the OB before glomerular formation. Surprisingly, OCAM was also expressed transiently by subsets of M/T cell dendrites located in the dorsal OB. The expression of OCAM by OSN axons and M/T dendrites was asymmetrical; in the dorsal OB, OCAM(-) OSN axons synapsed on OCAM(+) M/T dendrites, whereas in the ventral OB, OCAM(+) OSN axons synapsed on OCAM(-) M/T dendrites. The restricted spatial map of OCAM(+) M/T cells appeared earlier in development than the zonal segregation of OCAM(+) OSN axons. Thus, OCAM on M/T cell dendrites may act in a spatiotemporal window to specify regions of the developing rat OB, thereby establishing a foundation for mapping of the OE zonal organization onto the OB. Copyright 2003 Wiley-Liss, Inc.

  19. Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits.

    Directory of Open Access Journals (Sweden)

    Bryna Erblich

    Full Text Available The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R. Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1(op gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure.

  20. Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

    Science.gov (United States)

    Etgen, Anne M.; Dobrenis, Kostantin; Pollard, Jeffrey W.

    2011-01-01

    The brain contains numerous mononuclear phagocytes called microglia. These cells express the transmembrane tyrosine kinase receptor for the macrophage growth factor colony stimulating factor-1 (CSF-1R). Using a CSF-1R-GFP reporter mouse strain combined with lineage defining antibody staining we show in the postnatal mouse brain that CSF-1R is expressed only in microglia and not neurons, astrocytes or glial cells. To study CSF-1R function we used mice homozygous for a null mutation in the Csflr gene. In these mice microglia are >99% depleted at embryonic day 16 and day 1 post-partum brain. At three weeks of age this microglial depletion continues in most regions of the brain although some contain clusters of rounded microglia. Despite the loss of microglia, embryonic brain development appears normal but during the post-natal period the brain architecture becomes perturbed with enlarged ventricles and regionally compressed parenchyma, phenotypes most prominent in the olfactory bulb and cortex. In the cortex there is increased neuronal density, elevated numbers of astrocytes but reduced numbers of oligodendrocytes. Csf1r nulls rarely survive to adulthood and therefore to study the role of CSF-1R in olfaction we used the viable null mutants in the Csf1 (Csf1op) gene that encodes one of the two known CSF-1R ligands. Food-finding experiments indicate that olfactory capacity is significantly impaired in the absence of CSF-1. CSF-1R is therefore required for the development of microglia, for a fully functional olfactory system and the maintenance of normal brain structure. PMID:22046273

  1. Disrupted compartmental organization of axons and dendrites within olfactory glomeruli of mice deficient in the olfactory cell adhesion molecule, OCAM.

    Science.gov (United States)

    Walz, Andreas; Mombaerts, Peter; Greer, Charles A; Treloar, Helen B

    2006-01-01

    There is an overall topographic connectivity in the axonal projections of olfactory sensory neurons from the olfactory epithelium (OE) to the olfactory bulb (OB). The molecular determinants of this overall topographic OE-OB connectivity are not known. For 20 years, the intriguing expression pattern of the olfactory cell adhesion molecule (OCAM) has made it the leading candidate as determinant of overall topographic OE-OB connectivity. Here, we have generated a strain of OCAM knockout mice by gene targeting. There were no obvious alterations in the distribution of olfactory sensory neurons within the OE or in the coalescence of axons into specific glomeruli. However, the compartmental organization of dendrites and axons within the glomeruli was disrupted. Surprisingly, the mutant mice exhibited an increase in olfactory acuity; they appeared to have a better sense of smell. Thus, despite its striking expression pattern, OCAM is not essential for overall topographic OE-OB connectivity. Instead, OCAM is required for establishing or maintaining the compartmental organization and the segregation of axodendritic and dendrodendritic synapses within glomeruli.

  2. In Vivo Identification of Eugenol-Responsive and Muscone-Responsive Mouse Odorant Receptors

    Science.gov (United States)

    Adipietro, Kaylin; Titlow, William B.; Breheny, Patrick; Walz, Andreas; Mombaerts, Peter; Matsunami, Hiroaki

    2014-01-01

    Our understanding of mammalian olfactory coding has been impeded by the paucity of information about the odorant receptors (ORs) that respond to a given odorant ligand in awake, freely behaving animals. Identifying the ORs that respond in vivo to a given odorant ligand from among the ∼1100 ORs in mice is intrinsically challenging but critical for our understanding of olfactory coding at the periphery. Here, we report an in vivo assay that is based on a novel gene-targeted mouse strain, S100a5–tauGFP, in which a fluorescent reporter selectively marks olfactory sensory neurons that have been activated recently in vivo. Because each olfactory sensory neuron expresses a single OR gene, multiple ORs responding to a given odorant ligand can be identified simultaneously by capturing the population of activated olfactory sensory neurons and using expression profiling methods to screen the repertoire of mouse OR genes. We used this in vivo assay to re-identify known eugenol- and muscone-responsive mouse ORs. We identified additional ORs responsive to eugenol or muscone. Heterologous expression assays confirmed nine eugenol-responsive ORs (Olfr73, Olfr178, Olfr432, Olfr610, Olfr958, Olfr960, Olfr961, Olfr913, and Olfr1234) and four muscone-responsive ORs (Olfr74, Olfr235, Olfr816, and Olfr1440). We found that the human ortholog of Olfr235 and Olfr1440 responds to macrocyclic ketone and lactone musk odorants but not to polycyclic musk odorants or a macrocyclic diester musk odorant. This novel assay, called the Kentucky in vivo odorant ligand–receptor assay, should facilitate the in vivo identification of mouse ORs for a given odorant ligand of interest. PMID:25411495

  3. A TAP1 null mutation leads to an enlarged olfactory bulb and supernumerary, ectopic olfactory glomeruli

    Science.gov (United States)

    Salcedo, Ernesto; Cruz, Nicole M.; Ly, Xuan; Welander, Beth A.; Hanson, Kyle; Kronberg, Eugene; Restrepo, Diego

    2013-01-01

    Major histocompatibility class I (MHCI) molecules are well known for their immunological role in mediating tissue graft rejection. Recently, these molecules were discovered to be expressed in distinct neuronal subclasses, dispelling the long-held tenet that the uninjured brain is immune-privileged. Here, we show that MHCI molecules are expressed in the main olfactory bulb (MOB) of adult animals. Furthermore, we find that mice with diminished levels of MHCI expression have enlarged MOBs containing an increased number of small, morphologically abnormal and ectopically located P2 glomeruli. These findings suggest that MHCI molecules may play an important role in the proper formation of glomeruli in the bulb. PMID:23697805

  4. Induction of Associative Olfactory Memory by Targeted Activation of Single Olfactory Neurons in Drosophila Larvae

    OpenAIRE

    Takato Honda; Chi-Yu Lee; Maki Yoshida-Kasikawa; Ken Honjo; Katsuo Furukubo-Tokunaga

    2014-01-01

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by C...

  5. System identification of Drosophila olfactory sensory neurons.

    Science.gov (United States)

    Kim, Anmo J; Lazar, Aurel A; Slutskiy, Yevgeniy B

    2011-02-01

    The lack of a deeper understanding of how olfactory sensory neurons (OSNs) encode odors has hindered the progress in understanding the olfactory signal processing in higher brain centers. Here we employ methods of system identification to investigate the encoding of time-varying odor stimuli and their representation for further processing in the spike domain by Drosophila OSNs. In order to apply system identification techniques, we built a novel low-turbulence odor delivery system that allowed us to deliver airborne stimuli in a precise and reproducible fashion. The system provides a 1% tolerance in stimulus reproducibility and an exact control of odor concentration and concentration gradient on a millisecond time scale. Using this novel setup, we recorded and analyzed the in-vivo response of OSNs to a wide range of time-varying odor waveforms. We report for the first time that across trials the response of OR59b OSNs is very precise and reproducible. Further, we empirically show that the response of an OSN depends not only on the concentration, but also on the rate of change of the odor concentration. Moreover, we demonstrate that a two-dimensional (2D) Encoding Manifold in a concentration-concentration gradient space provides a quantitative description of the neuron's response. We then use the white noise system identification methodology to construct one-dimensional (1D) and two-dimensional (2D) Linear-Nonlinear-Poisson (LNP) cascade models of the sensory neuron for a fixed mean odor concentration and fixed contrast. We show that in terms of predicting the intensity rate of the spike train, the 2D LNP model performs on par with the 1D LNP model, with a root mean-square error (RMSE) increase of about 5 to 10%. Surprisingly, we find that for a fixed contrast of the white noise odor waveforms, the nonlinear block of each of the two models changes with the mean input concentration. The shape of the nonlinearities of both the 1D and the 2D LNP model appears to be

  6. Organization and distribution of glomeruli in the bowhead whale olfactory bulb

    Directory of Open Access Journals (Sweden)

    Takushi Kishida

    2015-04-01

    Full Text Available Although modern baleen whales (Mysticeti retain a functional olfactory system that includes olfactory bulbs, cranial nerve I and olfactory receptor genes, their olfactory capabilities have been reduced to a great degree. This reduction likely occurred as a selective response to their fully aquatic lifestyle. The glomeruli that occur in the olfactory bulb can be divided into two non-overlapping domains, a dorsal domain and a ventral domain. Recent molecular studies revealed that all modern whales have lost olfactory receptor genes and marker genes that are specific to the dorsal domain. Here we show that olfactory bulbs of bowhead whales (Balaena mysticetus lack glomeruli on the dorsal side, consistent with the molecular data. In addition, we estimate that there are more than 4,000 glomeruli elsewhere in the bowhead whale olfactory bulb, which is surprising given that bowhead whales possess only 80 intact olfactory receptor genes. Olfactory sensory neurons that express the same olfactory receptors in rodents generally project to two specific glomeruli in an olfactory bulb, implying an approximate 1:2 ratio of the number of olfactory receptors to the number of glomeruli. Here we show that this ratio does not apply to bowhead whales, reiterating the conceptual limits of using rodents as model organisms for understanding the initial coding of odor information among mammals.

  7. Using insect electroantennogram sensors on autonomous robots for olfactory searches.

    Science.gov (United States)

    Martinez, Dominique; Arhidi, Lotfi; Demondion, Elodie; Masson, Jean-Baptiste; Lucas, Philippe

    2014-08-04

    Robots designed to track chemical leaks in hazardous industrial facilities or explosive traces in landmine fields face the same problem as insects foraging for food or searching for mates: the olfactory search is constrained by the physics of turbulent transport. The concentration landscape of wind borne odors is discontinuous and consists of sporadically located patches. A pre-requisite to olfactory search is that intermittent odor patches are detected. Because of its high speed and sensitivity, the olfactory organ of insects provides a unique opportunity for detection. Insect antennae have been used in the past to detect not only sex pheromones but also chemicals that are relevant to humans, e.g., volatile compounds emanating from cancer cells or toxic and illicit substances. We describe here a protocol for using insect antennae on autonomous robots and present a proof of concept for tracking odor plumes to their source. The global response of olfactory neurons is recorded in situ in the form of electroantennograms (EAGs). Our experimental design, based on a whole insect preparation, allows stable recordings within a working day. In comparison, EAGs on excised antennae have a lifetime of 2 hr. A custom hardware/software interface was developed between the EAG electrodes and a robot. The measurement system resolves individual odor patches up to 10 Hz, which exceeds the time scale of artificial chemical sensors. The efficiency of EAG sensors for olfactory searches is further demonstrated in driving the robot toward a source of pheromone. By using identical olfactory stimuli and sensors as in real animals, our robotic platform provides a direct means for testing biological hypotheses about olfactory coding and search strategies. It may also prove beneficial for detecting other odorants of interests by combining EAGs from different insect species in a bioelectronic nose configuration or using nanostructured gas sensors that mimic insect antennae.

  8. Early olfactory environment influences social behaviour in adult Octodon degus.

    Directory of Open Access Journals (Sweden)

    Natalia Márquez

    Full Text Available We evaluated the extent to which manipulation of early olfactory environment can influence social behaviours in the South American Hystricognath rodent Octodon degus. The early olfactory environment of newborn degus was manipulated by scenting all litter members with eucalyptol during the first month of life. The social behaviour of sexually mature animals (5-7 months old towards conspecifics was then assessed using a y-maze to compare the response of control (naïve and treated animals to two different olfactory configurations (experiment 1: (i a non-familiarized conspecific impregnated with eucalyptol (eucalyptol arm presented against (ii a non-familiarized unscented conspecific (control arm. In addition, in dyadic encounters, we assessed the behaviour of control and eucalyptol treated animals towards a non-familiarized conspecific scented with eucalyptol (experiment 2. We found that control subjects explored and spent significantly less time in the eucalyptol arm, indicating neophobic behaviours towards the artificially scented conspecific. Treated subjects explored and spent similar time in both arms of the maze, showing the same interest for both olfactory stimuli presented. During dyadic encounters in experiment 2, an interaction effect between early experience and sex was observed. Control males escaped and avoided their scented partner more frequently than eucalyptol treated male subjects and than females. Both groups did not differ in the exploration of their scented partners, suggesting that avoidance within agonistic context does not relate to neophobic behaviours. Our results suggest that the exposure to eucalyptol during early ontogeny decreases evasive behaviours within an agonistic context as a result of olfactory learning. Altogether, these results indicate that olfactory cues learned in early ontogeny can influence olfactory-guided behaviours in adult degus.

  9. Ethmoidectomy combined with superior meatus enlargement increases olfactory airflow

    Science.gov (United States)

    Kondo, Kenji; Nomura, Tsutomu; Yamasoba, Tatsuya

    2017-01-01

    Objectives The relationship between a particular surgical technique in endoscopic sinus surgery (ESS) and airflow changes in the post‐operative olfactory region has not been assessed. The present study aimed to compare olfactory airflow after ESS between conventional ethmoidectomy and ethmoidectomy with superior meatus enlargement, using virtual ESS and computational fluid dynamics (CFD) analysis. Study Design Prospective computational study. Materials and Methods Nasal computed tomography images of four adult subjects were used to generate models of the nasal airway. The original preoperative model was digitally edited as virtual ESS by performing uncinectomy, ethmoidectomy, antrostomy, and frontal sinusotomy. The following two post‐operative models were prepared: conventional ethmoidectomy with normal superior meatus (ESS model) and ethmoidectomy with superior meatus enlargement (ESS‐SM model). The calculated three‐dimensional nasal geometries were confirmed using virtual endoscopy to ensure that they corresponded to the post‐operative anatomy observed in the clinical setting. Steady‐state, laminar, inspiratory airflow was simulated, and the velocity, streamline, and mass flow rate in the olfactory region were compared among the preoperative and two postoperative models. Results The mean velocity in the olfactory region, number of streamlines bound to the olfactory region, and mass flow rate were higher in the ESS‐SM model than in the other models. Conclusion We successfully used an innovative approach involving virtual ESS, virtual endoscopy, and CFD to assess postoperative outcomes after ESS. It is hypothesized that the increased airflow to the olfactory fossa achieved with ESS‐SM may lead to improved olfactory function; however, further studies are required. Level of Evidence NA. PMID:28894833

  10. Mouse phenotyping.

    Science.gov (United States)

    Fuchs, Helmut; Gailus-Durner, Valérie; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Da Silva-Buttkus, Patricia; Neff, Frauke; Götz, Alexander; Hans, Wolfgang; Hölter, Sabine M; Horsch, Marion; Kastenmüller, Gabi; Kemter, Elisabeth; Lengger, Christoph; Maier, Holger; Matloka, Mikolaj; Möller, Gabriele; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Römisch-Margl, Werner; Rozman, Jan; Wang-Sattler, Rui; Schrewe, Anja; Stöger, Claudia; Tost, Monica; Adamski, Jerzy; Aigner, Bernhard; Beckers, Johannes; Behrendt, Heidrun; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Illig, Thomas; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Kremmer, Elisabeth; Mempel, Martin; Neschen, Susanne; Ollert, Markus; Schulz, Holger; Suhre, Karsten; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Hrabě de Angelis, Martin

    2011-02-01

    Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/[2]). Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Effects of olfactory sense on chocolate craving.

    Science.gov (United States)

    Firmin, Michael W; Gillette, Aubrey L; Hobbs, Taylor E; Wu, Di

    2016-10-01

    In the present study, we assessed the effect of the olfactory sense on chocolate craving in college females. Building on previous research by Kemps and Tiggemann (2013), we hypothesized that a fresh scent would decrease one's craving level for chocolate food. While the precursor study only addressed the decrease of chocolate craving, we also hypothesized that a sweet scent would increase one's craving level for chocolate foods. In the present experiment, participants rated their craving levels after viewing images of chocolate foods and inhaling essential oils: one fresh (Slique™ essence), and one sweet (vanilla). Results supported both of the hypotheses: inhaling a fresh scent reduced females' craving levels; similarly, when a sweet scent was inhaled, the participants' craving levels for chocolate food increased. These findings are particularly beneficial for women seeking weight loss and the findings can be applied in contexts such as weight loss programs, therapy, and maintenance programs, even beyond college settings. The results are particularly useful for helping women regarding stimuli that might serve as triggers for chocolate cravings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Active forgetting of olfactory memories in Drosophila.

    Science.gov (United States)

    Berry, Jacob A; Davis, Ronald L

    2014-01-01

    Failure to remember, or forgetting, is a phenomenon familiar to everyone and despite more than a century of scientific inquiry, why we forget what we once knew remains unclear. If the brain marshals significant resources to form and store memories, why is it that these memories become lost? In the last century, psychological studies have divided forgetting into decay theory, in which memory simply dissipates with time, and interference theory, in which additional learning or mental activity hinders memory by reducing its stability or retrieval (for review, Dewar et al., 2007; Wixted, 2004). Importantly, these psychological models of forgetting posit that forgetting is a passive property of the brain and thus a failure of the brain to retain memories. However, recent neuroscience research on olfactory memory in Drosophila has offered evidence for an alternative conclusion that forgetting is an "active" process, with specific, biologically regulated mechanisms that remove existing memories (Berry et al., 2012; Shuai et al., 2010). Similar to the bidirectional regulation of cell number by mitosis and apoptosis, protein concentration by translation and lysosomal or proteomal degradation, and protein phosphate modification by kinases and phosphatases, biologically regulated memory formation and removal would be yet another example in biological systems where distinct and separate pathways regulate the creation and destruction of biological substrates. © 2014 Elsevier B.V. All rights reserved.

  13. Dynamic properties of Drosophila olfactory electroantennograms.

    Science.gov (United States)

    Schuckel, Julia; Meisner, Shannon; Torkkeli, Päivi H; French, Andrew S

    2008-05-01

    Time-dependent properties of chemical signals are probably crucially important to many animals, but little is known about the dynamics of chemoreceptors. Behavioral evidence of dynamic sensitivity includes the control of moth flight by pheromone plume structure, and the ability of some blood-sucking insects to detect varying concentrations of carbon dioxide, possibly matched to host breathing rates. Measurement of chemoreceptor dynamics has been limited by the technical challenge of producing controlled, accurate modulation of olfactory and gustatory chemical concentrations over suitably wide ranges of amplitude and frequency. We used a new servo-controlled laminar flow system, combined with photoionization detection of surrogate tracer gas, to characterize electroantennograms (EAG) of Drosophila antennae during stimulation with fruit odorants or aggregation pheromone in air. Frequency response functions and coherence functions measured over a bandwidth of 0-100 Hz were well characterized by first-order low-pass linear filter functions. Filter time constant varied over almost a tenfold range, and was characteristic for each odorant, indicating that several dynamically different chemotransduction mechanisms are present. Pheromone response was delayed relative to fruit odors. Amplitude of response, and consequently signal-to-noise ratio, also varied consistently with different compounds. Accurate dynamic characterization promises to provide important new information about chemotransduction and odorant-stimulated behavior.

  14. Volumetric study of the olfactory bulb in patients with chronic rhinonasal sinusitis using MRI

    Directory of Open Access Journals (Sweden)

    Reda A. Alarabawy

    2016-06-01

    Conclusions: MRI with volumetric analysis is a useful tool in assessment of the olfactory bulb volume in patients with olfactory loss and appears to be of help in assessment of the degree of recovery in patients after sinus surgery.

  15. Beta and gamma oscillatory activities associated with olfactory memory tasks: different rhythms for different functional networks?

    National Research Council Canada - National Science Library

    Martin, Claire; Ravel, Nadine

    2014-01-01

    .... The anatomy of the olfactory network (olfactory bulb, piriform, and entorhinal cortices) and its unique direct access to the limbic system makes it particularly attractive to study how sensory processing could be modulated by learning and memory...

  16. No evidence for visual context-dependency of olfactory learning in Drosophila

    Science.gov (United States)

    Yarali, Ayse; Mayerle, Moritz; Nawroth, Christian; Gerber, Bertram

    2008-08-01

    How is behaviour organised across sensory modalities? Specifically, we ask concerning the fruit fly Drosophila melanogaster how visual context affects olfactory learning and recall and whether information about visual context is getting integrated into olfactory memory. We find that changing visual context between training and test does not deteriorate olfactory memory scores, suggesting that these olfactory memories can drive behaviour despite a mismatch of visual context between training and test. Rather, both the establishment and the recall of olfactory memory are generally facilitated by light. In a follow-up experiment, we find no evidence for learning about combinations of odours and visual context as predictors for reinforcement even after explicit training in a so-called biconditional discrimination task. Thus, a ‘true’ interaction between visual and olfactory modalities is not evident; instead, light seems to influence olfactory learning and recall unspecifically, for example by altering motor activity, alertness or olfactory acuity.

  17. Heightened Olfactory Sensitivity in Young Females with Recent-Onset Anorexia Nervosa and Recovered Individuals

    DEFF Research Database (Denmark)

    Bentz, Mette; Guldberg, Johanne; Vangkilde, Signe

    2017-01-01

    INTRODUCTION: Olfaction may be related to food restriction and weight loss. However, reports regarding olfactory function in individuals with anorexia nervosa (AN) have been inconclusive. OBJECTIVE: Characterize olfactory sensitivity and identification in female adolescents and young adults...

  18. Analytical processing of binary mixture information by olfactory bulb glomeruli.

    Directory of Open Access Journals (Sweden)

    Max L Fletcher

    Full Text Available Odors are rarely composed of a single compound, but rather contain a large and complex variety of chemical components. Often, these mixtures are perceived as having unique qualities that can be quite different than the combination of their components. In many cases, a majority of the components of a mixture cannot be individually identified. This synthetic processing of odor information suggests that individual component representations of the mixture must interact somewhere along the olfactory pathway. The anatomical nature of sensory neuron input into segregated glomeruli with the bulb suggests that initial input of odor information into the bulb is analytic. However, a large network of interneurons within the olfactory bulb could allow for mixture interactions via mechanisms such as lateral inhibition. Currently in mammals, it is unclear if postsynaptic mitral/tufted cell glomerular mixture responses reflect the analytical mixture input, or provide the initial basis for synthetic processing with the olfactory system. To address this, olfactory bulb glomerular binary mixture representations were compared to representations of each component using transgenic mice expressing the calcium indicator G-CaMP2 in olfactory bulb mitral/tufted cells. Overall, dorsal surface mixture representations showed little mixture interaction and often appeared as a simple combination of the component representations. Based on this, it is concluded that dorsal surface glomerular mixture representations remain largely analytical with nearly all component information preserved.

  19. Neuronal basis of innate olfactory attraction to ethanol in Drosophila.

    Directory of Open Access Journals (Sweden)

    Andrea Schneider

    Full Text Available The decision to move towards a mating partner or a food source is essential for life. The mechanisms underlying these behaviors are not well understood. Here, we investigated the role of octopamine - the invertebrate analogue of noradrenaline - in innate olfactory attraction to ethanol. We confirmed that preference is caused via an olfactory stimulus by dissecting the function of the olfactory co-receptor Orco (formally known as OR83b. Orco function is not required for ethanol recognition per se, however it plays a role in context dependent recognition of ethanol. Odor-evoked ethanol preference requires the function of Tbh (Tyramine β hydroxalyse, the rate-limiting enzyme of octopamine synthesis. In addition, neuronal activity in a subset of octopaminergic neurons is necessary for olfactory ethanol preference. Notably, a specific neuronal activation pattern of tyraminergic/octopaminergic neurons elicit preference and is therefore sufficient to induce preference. In contrast, dopamine dependent increase in locomotor activity is not sufficient for olfactory ethanol preference. Consistent with the role of noradrenaline in mammalian drug induced rewards, we provide evidence that in adult Drosophila the octopaminergic neurotransmitter functions as a reinforcer and that the molecular dissection of the innate attraction to ethanol uncovers the basic properties of a response selection system.

  20. From chemical neuroanatomy to an understanding of the olfactory system

    Directory of Open Access Journals (Sweden)

    L. Oboti

    2011-10-01

    Full Text Available The olfactory system is the appropriate model for studying several aspects of neuronal physiology spanning from the developmental stage to neural network remodelling in the adult brain. Both the morphological and physiological understanding of this system were strongly supported by classical histochemistry. It is emblematic the case of the Olfactory Marker Protein (OMP staining, the first, powerful marker for fully differentiated olfactory receptor neurons and a key tool to investigate the dynamic relations between peripheral sensory epithelia and central relay regions given its presence within olfactory fibers reaching the olfactory bulb (OB. Similarly, the use of thymidine analogues was able to show neurogenesis in an adult mammalian brain far before modern virus labelling and lipophilic tracers based methods. Nowadays, a wealth of new histochemical techniques combining cell and molecular biology approaches is available, giving stance to move from the analysis of the chemically identified circuitries to functional research. The study of adult neurogenesis is indeed one of the best explanatory examples of this statement. After defining the cell types involved and the basic physiology of this phenomenon in the OB plasticity, we can now analyze the role of neurogenesis in well testable behaviours related to socio-chemical communication in rodents.

  1. Olfactory insights into sleep-dependent learning and memory.

    Science.gov (United States)

    Shanahan, Laura K; Gottfried, Jay A

    2014-01-01

    Sleep is pervasive throughout most of the animal kingdom-even jellyfish and honeybees do it. Although the precise function of sleep remains elusive, research increasingly suggests that sleep plays a key role in memory consolidation. Newly formed memories are highly labile and susceptible to interference, and the sleep period offers an optimal window in which memories can be strengthened or modified. Interestingly, a small but growing research area has begun to explore the ability of odors to modulate memories during sleep. The unique anatomical organization of the olfactory system, including its intimate overlap with limbic systems mediating emotion and memory, and the lack of a requisite thalamic intermediary between the nasal periphery and olfactory cortex, suggests that odors may have privileged access to the brain during sleep. Indeed, it has become clear that the long-held assumption that odors have no impact on the sleeping brain is no longer tenable. Here, we summarize recent studies in both animal and human models showing that odor stimuli experienced in the waking state modulate olfactory cortical responses in sleep-like states, that delivery of odor contextual cues during sleep can enhance declarative memory and extinguish fear memory, and that olfactory associative learning can even be achieved entirely within sleep. Data reviewed here spotlight the emergence of a new research area that should hold far-reaching implications for future neuroscientific investigations of sleep, learning and memory, and olfactory system function. © 2014 Elsevier B.V. All rights reserved.

  2. Insect olfactory receptors: contributions of molecular biology to chemical ecology.

    Science.gov (United States)

    Jacquin-Joly, Emmanuelle; Merlin, Christine

    2004-12-01

    Our understanding of the molecular basis of chemical signal recognition in insects has been greatly expanded by the recent discovery of olfactory receptors (Ors). Since the discovery of the complete repertoire of Drosophila melanogaster Ors, candidate Ors have been identified from at least 12 insect species from four orders (Coleoptera, Lepidoptera, Diptera, and Hymenoptera), including species of economic or medical importance. Although all Ors share the same G-protein coupled receptor structure with seven transmembrane domains, they present poor sequence homologies within and between species, and have been identified mainly through genomic data analyses. To date, D. melanogaster remains the only insect species where Ors have been extensively studied, from expression pattern establishment to functional investigations. These studies have confirmed several observations made in vertebrates: one Or type is selectively expressed in a subtype of olfactory receptor neurons, and one olfactory neuron expresses only one type of Or. In addition, all olfactory neurons expressing one Or type converge to the same glomerulus in the antennal lobe. The olfactory mechanism, thus, appears to be conserved between insects and vertebrates. Although Or functional studies are in their initial stages in insects (mainly Drosophila), insects appear to be good models to establish fundamental concepts of olfaction with the development of powerful genetic, imaging, and behavioral tools. This new field of study will greatly contribute to the understanding of insect chemical communication mechanisms, particularly with agricultural pests and disease vectors, and could result in future strategies to reduce their negative effects.

  3. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

    Science.gov (United States)

    Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano, Jorge M.

    2015-01-01

    The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID:26380118

  4. Classical olfactory conditioning in the oriental fruit fly, Bactrocera dorsalis.

    Directory of Open Access Journals (Sweden)

    Jia Li Liu

    Full Text Available The oriental fruit fly, Bactrocera dorsalis, is a serious pest of fruits and vegetables. Methyl eugenol (ME, a male attractant, is used to against this fly by mass trapping. Control effect may be influenced by learning, which could modify the olfactory response of the fly to this attractant. To collect the behavioral evidence, studies on the capability of this fly for olfactory learning are necessary. We investigated olfactory learning in male flies with a classical olfactory conditioning procedure using restrained individuals under laboratory conditions. The acquisition of the proboscis extension reflex was used as the criterion for conditioning. A high conditioned response level was found in oriental fruit flies when an odor was presented in paired association with a sucrose reward but not when the odor and sucrose were presented unpaired. We also found that the conditioning performance was influenced by the odor concentration, intertrial interval, and starvation time. A slight sensitization elicited by imbibing sucrose was observed. These results indicate that oriental fruit flies have a high capacity to form an olfactory memory as a result of classical conditioning.

  5. Evaluation of Olfactory and Gustatory Function of HIV Infected Women

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    Ayotunde James Fasunla

    2016-01-01

    Full Text Available Background. Compliance with medication requires good sense of smell and taste. Objective. To evaluate the olfactory and gustatory function of HIV infected women in Ibadan, Nigeria. Methods. A case control study of women comprising 83 HIV infected women and 79 HIV uninfected women. Subjective self-rating of taste and smell function was by visual analogue scale. Olfactory function was measured via olfactory threshold (OT, olfactory discrimination (OD, olfactory identification (OI, and TDI using “Sniffin’ sticks” kits and taste function (Total Taste Strips (TTS score measurement was by taste strips. Results. The mean age of the HIV infected women was 43.67 years ± 10.72 and control was 41.48 years ± 10.99. There was no significant difference in the self-reported assessment of smell (p=0.67 and taste (p=0.84 of HIV infected and uninfected women. Although the mean OT, OD, OI, TDI, and TTS scores of HIV infected and uninfected women were within the normosmic and normogeusic values, the values were significantly higher in the controls (p<0.05. Hyposmia was in 39.7% of subjects and 12.6% of controls while hypogeusia was in 15.7% of subjects and 1.3% of controls. Conclusions. Hyposmia and hypogeusia are commoner among the HIV infected women than the HIV uninfected women and the risk increases with an increased duration of highly active antiretroviral therapy.

  6. Nutrient Sensing: Another Chemosensitivity of the Olfactory System

    Directory of Open Access Journals (Sweden)

    A-Karyn Julliard

    2017-07-01

    Full Text Available Olfaction is a major sensory modality involved in real time perception of the chemical composition of the external environment. Olfaction favors anticipation and rapid adaptation of behavioral responses necessary for animal survival. Furthermore, recent studies have demonstrated that there is a direct action of metabolic peptides on the olfactory network. Orexigenic peptides such as ghrelin and orexin increase olfactory sensitivity, which in turn, is decreased by anorexigenic hormones such as insulin and leptin. In addition to peptides, nutrients can play a key role on neuronal activity. Very little is known about nutrient sensing in olfactory areas. Nutrients, such as carbohydrates, amino acids, and lipids, could play a key role in modulating olfactory sensitivity to adjust feeding behavior according to metabolic need. Here we summarize recent findings on nutrient-sensing neurons in olfactory areas and delineate the limits of our knowledge on this topic. The present review opens new lines of investigations on the relationship between olfaction and food intake, which could contribute to determining the etiology of metabolic disorders.

  7. Phosphoinositide 3-kinase mediated signaling in lobster olfactory receptor neurons

    Science.gov (United States)

    Corey, Elizabeth A.; Bobkov, Yuriy; Pezier, Adeline; Ache, Barry W.

    2010-01-01

    In vertebrates and some invertebrates, odorant molecules bind to G protein-coupled receptors (GPCRs) on olfactory receptor neurons (ORNs) to initiate signal transduction. Phosphoinositide 3-kinase (PI3K) activity has been implicated physiologically in olfactory signal transduction, suggesting a potential role for a GPCR-activated class I PI3K. Using isoform-specific antibodies, we identified a protein in the olfactory signal transduction compartment of lobster ORNs that is antigenically similar to mammalian PI3Kγ and cloned a gene for a PI3K with amino acid homology with PI3Kβ. The lobster olfactory PI3K co-immunoprecipitates with the G protein α and β subunits, and an odorant-evoked increase in phosphatidylinositol (3,4,5)-trisphosphate can be detected in the signal transduction compartment of the ORNs. PI3Kγ and β isoform-specific inhibitors reduce the odorant-evoked output of lobster ORNs in vivo. Collectively, these findings provide evidence that PI3K is indeed activated by odorant receptors in lobster ORNs and further support the potential involvement of G protein activated PI3K signaling in olfactory transduction. PMID:20132480

  8. Properties and mechanisms of olfactory learning and memory

    Directory of Open Access Journals (Sweden)

    Michelle T Tong

    2014-07-01

    Full Text Available Memories are dynamic physical phenomena with psychometric forms as well as characteristic timescales. Most of our understanding of the cellular mechanisms underlying the neurophysiology of memory, however, derives from one-trial learning paradigms that, while powerful, do not fully embody the gradual, representational, and statistical aspects of cumulative learning. The early olfactory system -- particularly olfactory bulb -- comprises a reasonably well-understood and experimentally accessible neuronal network with intrinsic plasticity that underlies both one-trial (adult aversive, neonatal and cumulative (adult appetitive odor learning. These olfactory circuits employ many of the same molecular and structural mechanisms of memory as, for example, hippocampal circuits following inhibitory avoidance conditioning, but the temporal sequences of post-conditioning molecular events are likely to differ owing to the need to incorporate new information from ongoing learning events into the evolving memory trace. Moreover, the shapes of acquired odor representations, and their gradual transformation over the course of cumulative learning, also can be directly measured, adding an additional representational dimension to the traditional metrics of memory strength and persistence. In this review, we describe some established molecular and structural mechanisms of memory with a focus on the timecourses of post-conditioning molecular processes. We describe the properties of odor learning intrinsic to the olfactory bulb and review the utility of the olfactory system of adult rodents as a memory system in which to study the cellular mechanisms of cumulative learning.

  9. Sad man's nose: Emotion induction and olfactory perception.

    Science.gov (United States)

    Flohr, Elena L R; Erwin, Elena; Croy, Ilona; Hummel, Thomas

    2017-03-01

    Emotional and olfactory processing is frequently shown to be closely linked both anatomically and functionally. Depression, a disease closely related to the emotional state of sadness, has been shown to be associated with a decrease in olfactory sensitivity. The present study focuses on the state of sadness in n = 31 healthy subjects in order to investigate the specific contribution of this affective state in the modulation of olfactory processing. A sad or indifferent affective state was induced using 2 movies that were presented on 2 separate days. Afterward, chemosensory-evoked potentials were recorded after stimulation with an unpleasant (hydrogen sulfide: "rotten eggs") or a pleasant (phenyl ethyl alcohol: "rose") odorant. Latencies of N1 and P2 peaks were longer after induction of the sad affective state. Additionally, amplitudes were lower in a sad affective state when being stimulated with the unpleasant odorant. Processing of olfactory input has thus been reduced under conditions of the sad affective state. We argue that the affective state per se could at least partially account for the reduced olfactory sensitivity in depressed patients. To our knowledge, the present study is the first to show influence of affective state on chemosensory event-related potentials. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  10. Olfactory auras caused by a very focal isolated epileptic network in the amygdala

    Directory of Open Access Journals (Sweden)

    Tadashi Hamasaki

    2014-01-01

    Full Text Available Epileptic olfactory auras manifesting as simple partial seizures are rare. We report a patient who presented with olfactory auras after hemorrhage from a cavernous angioma in the left mesial temporal region. His olfactory auras persisted 12 years after two surgeries for a cavernous angioma. Intracranial depth electrodes revealed a very focal isolated epileptogenic zone in the amygdala. Olfactory auras were successfully treated by focus resection.

  11. Correlated basal expression of immediate early gene egr1 and tyrosine hydroxylase in zebrafish brain and downregulation in olfactory bulb after transitory olfactory deprivation.

    Science.gov (United States)

    Kress, Sigrid; Wullimann, Mario F

    2012-12-01

    Imprinting on kin occurs during the sixth day of larval development in zebrafish and depends on olfactory signals. In rodents, the immediate early gene egr1 is involved in maintaining the dopaminergic phenotype of periglomerular olfactory bulb cells in an activity dependent way. Furthermore, egr1 is upregulated in medial amygdalar dopamine cells in some rodents (prairie voles) dependent on social pheromone interactions. Thus, we aimed to investigate whether egr1 is involved in imprinting processes and later kin recognition in zebrafish in olfactory centers, such as the olfactory bulb and suspected medial amygdala. In the present paper, we focus on a basic investigation of basal egr1 expression throughout zebrafish brain development and its co-localization with tyrosine hydroxylase as a marker for dopaminergic neurons. Indeed, there is unambiguous co-localization of egr1 and tyrosine hydroxylase in the zebrafish olfactory bulb and hypothetical medial amygdala. Furthermore, as in rodents, ipsilateral transient olfactory deprivation through Triton X-100 treatment of the olfactory epithelium leads to downregulation of egr1 and tyrosine hydroxylase expression in the olfactory bulb, but apparently not in secondary olfactory targets of the zebrafish brain. This indicates that similar processes might be at work in zebrafish and rodent olfactory systems, but their more specific involvement in imprinting in zebrafish has to be further tested. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Evaluation of the olfactory bulb volume and olfactory threshold in patients with nasal polyps and impact of functional endoscopic sinus surgery: a longitudinal study.

    Science.gov (United States)

    Sadeghi, Mohammad; Amali, Amin; Ezabadi, Sara Rahavi; Motiee-Langroudi, Maziar; Farshchi, Samireh; Mokhtari, Zahra

    2015-04-01

    Debate still persists on the relation between olfactory bulb volume (OBV) and olfactory function. Many studies suggest that olfactory deprivation decreases the OBV. The aim of this study was to compare the olfactory threshold and OBV of patients with nasal polyps to healthy individuals and to evaluate the impact of functional endoscopic sinus surgery (FESS) on OBV and olfactory threshold. A longitudinal study was carried out in Tehran between 2011 and 2012. Twenty-two patients with nasal polyps were compared with 37 healthy individuals. Olfactory threshold test and magnetic resonance imaging (MRI) were performed on all participants. Twenty-two patients in case group were followed for 6 months after FESS. OBV and olfactory threshold were measured after 6 months. There was no significant difference between the age, gender, and OBV of the 2 groups. However, the difference between olfactory threshold was significant (p = 0.005). The olfactory threshold showed no significant relation with OBV (p > 0.05). The correlation between Lund-Mackay score and the mean total OBV and left OBV was significant (r = -0.15, p = 0.045; r = -0.22, p = 0.047; respectively). The decrease in olfactory threshold measured after FESS was statistically significant. Right, left, and total OBV significantly increased after FESS. The results of our study show that FESS has a significant impact on OBV increment and olfactory threshold decrement. The olfactory bulb is a plastic structure and improvement in peripheral olfactory function results in increase in OBV. However, further studies are mandated, in order to establish this result. © 2015 ARS-AAOA, LLC.

  13. Executive function and memory in relation to olfactory deficits in alcohol-dependent patients.

    Science.gov (United States)

    Rupp, Claudia I; Fleischhacker, W Wolfgang; Drexler, Arthur; Hausmann, Armand; Hinterhuber, Hartmann; Kurz, Martin

    2006-08-01

    Prior research indicates that chronic alcoholism is accompanied by olfactory deficits. These have been suggested to reflect dysfunctions in olfactory brain regions. The present study investigated the role of neurocognitive functioning in tests (executive function and memory) sensitive to the functional integrity of brain areas that are crucial to olfactory processing in patients with alcohol dependence. Performance on olfactory functions (detection threshold, quality discrimination, identification), executive function (Wisconsin Card Sorting Test), and memory (German version of the California Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30 healthy comparison subjects, comparable in age, gender, and smoking status. Compared with controls, alcohol-dependent patients were impaired in all 3 domains, olfactory functions, executive function, and memory. In patients, olfactory discrimination ability was positively correlated with executive function performance. Regression analyses conducted to clarify the relation between group (patients vs controls), executive function, memory, and olfactory functions indicated that group was the only significant predictor of olfactory detection threshold and identification, and both group and executive function were found to be the significant predictors of olfactory discrimination. Olfactory deficits in alcohol dependence appear to be associated with prefrontal cognitive dysfunction. Results indicate that olfactory quality discrimination deficits are related to executive function impairment. These findings add to the available research on frontal lobe dysfunction in alcoholism, suggesting that alcohol-related olfactory discrimination deficits may be associated with impairment in the functional integrity of the prefrontal lobe.

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  1. Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice.

    Science.gov (United States)

    Zhang, Zhe; Yang, Dong; Zhang, Mengdi; Zhu, Ning; Zhou, Yanfen; Storm, Daniel R; Wang, Zhenshan

    2017-01-01

    Type 3 adenylyl cyclase (Adcy3) is localized to the cilia of olfactory sensory neurons (OSNs) and is an essential component of the olfactory cyclic adenosine monophosphate (cAMP) signaling pathway. Although the role of this enzyme in odor detection and axonal projection in OSNs was previously characterized, researchers will still have to determine its function in the maturation of postnatal OSNs and olfactory cilium ultrastructure. Previous studies on newborns showed that the anatomic structure of the main olfactory epithelium (MOE) of Adcy3 knockout mice ( Adcy3 -/- ) is indistinguishable from that of their wild-type littermates ( Adcy3 +/+ ), whereas the architecture and associated composition of MOE are relatively underdeveloped at this early age. The full effects of sensory deprivation on OSNs may not also be exhibited in such age. In the present study, following a comparison of postnatal OSNs in seven-, 30-, and 90-day-old Adcy3 -/- mice and wild-type controls ( Adcy 3 +/+ ), we observed that the absence of Adcy3 leads to cumulative defects in the maturation of OSNs. Upon aging, Adcy3 -/- OSNs exhibited increase in immature cells and reduction in mature cells along with elevated apoptosis levels. The density and ultrastructure of Adcy3 -/- cilia were also disrupted in mice upon aging. Collectively, our results reveal an indispensable role of Adcy3 in postnatal maturation of OSNs and maintenance of olfactory cilium ultrastructure in mice through adulthood.

  2. Effect of flumethrin on survival and olfactory learning in honeybees.

    Science.gov (United States)

    Tan, Ken; Yang, Shuang; Wang, Zhengwei; Menzel, Randolf

    2013-01-01

    Flumethrin has been widely used as an acaricide for the control of Varroa mites in commercial honeybee keeping throughout the world for many years. Here we test the mortality of the Asian honeybee Apis cerana cerana after treatment with flumethrin. We also ask (1) how bees react to the odor of flumethrin, (2) whether its odor induces an innate avoidance response, (3) whether its taste transmits an aversive reinforcing component in olfactory learning, and (4) whether its odor or taste can be associated with reward in classical conditioning. Our results show that flumethrin has a negative effect on Apis ceranàs lifespan, induces an innate avoidance response, acts as a punishing reinforcer in olfactory learning, and interferes with the association of an appetitive conditioned stimulus. Furthermore flumethrin uptake within the colony reduces olfactory learning over an extended period of time.

  3. Neuronal circuits and computations: pattern decorrelation in the olfactory bulb.

    Science.gov (United States)

    Friedrich, Rainer W; Wiechert, Martin T

    2014-08-01

    Neuronal circuits in the olfactory bulb transform odor-evoked activity patterns across the input channels, the olfactory glomeruli, into distributed activity patterns across the output neurons, the mitral cells. One computation associated with this transformation is a decorrelation of activity patterns representing similar odors. Such a decorrelation has various benefits for the classification and storage of information by associative networks in higher brain areas. Experimental results from adult zebrafish show that pattern decorrelation involves a redistribution of activity across the population of mitral cells. These observations imply that pattern decorrelation cannot be explained by a global scaling mechanism but that it depends on interactions between distinct subsets of neurons in the network. This article reviews insights into the network mechanism underlying pattern decorrelation and discusses recent results that link pattern decorrelation in the olfactory bulb to odor discrimination behavior. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Self-grounding visual, auditory and olfactory autobiographical memories.

    Science.gov (United States)

    Knez, Igor; Ljunglöf, Louise; Arshamian, Artin; Willander, Johan

    2017-07-01

    Given that autobiographical memory provides a cognitive foundation for the self, we investigated the relative importance of visual, auditory and olfactory autobiographical memories for the self. Thirty subjects, with a mean age of 35.4years, participated in a study involving a three×three within-subject design containing nine different types of autobiographical memory cues: pictures, sounds and odors presented with neutral, positive and negative valences. It was shown that visual compared to auditory and olfactory autobiographical memories involved higher cognitive and emotional constituents for the self. Furthermore, there was a trend showing positive autobiographical memories to increase their proportion to both cognitive and emotional components of the self, from olfactory to auditory to visually cued autobiographical memories; but, yielding a reverse trend for negative autobiographical memories. Finally, and independently of modality, positive affective states were shown to be more involved in autobiographical memory than negative ones. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Of mice and men: olfactory neuroblastoma among animals and humans.

    Science.gov (United States)

    Lubojemska, A; Borejko, M; Czapiewski, P; Dziadziuszko, R; Biernat, W

    2016-09-01

    Olfactory neuroblastoma (ONB) is a rare tumour of nasal cavity and paranasal sinuses that arises from the olfactory neuroepithelium and has unpredictable clinical course. As the sense of smell is phylogenetically one of the first senses and olfactory neuroepithelium is evolutionary conserved with striking similarities among different species, we performed an extensive analysis of the literature in order to evaluate the similarities and differences between animals and humans on the clinical, morphological, immunohistochemical, ultrastructural and molecular level. Our analysis revealed that ONB was reported mainly in mammals and showed striking similarities to human ONB. These observations provide rationale for introduction of therapy modalities used in humans into the veterinary medicine. Animal models of neuroblastoma should be considered for the preclinical studies evaluating novel therapies for ONB. © 2014 John Wiley & Sons Ltd.

  6. Evidence for a Peripheral Olfactory Memory in Imprinted Salmon

    Science.gov (United States)

    Nevitt, Gabrielle A.; Dittman, Andrew H.; Quinn, Thomas P.; Moody, William J., Jr.

    1994-05-01

    The remarkable homing ability of salmon relies on olfactory cues, but its cellular basis is unknown. To test the role of peripheral olfactory receptors in odorant memory retention, we imprinted coho salmon (Oncorhynchus kisutch) to micromolar concentrations of phenyl ethyl alcohol during parr-smolt transformation. The following year, we measured phenyl ethyl alcohol responses in the peripheral receptor cells using patch clamp. Cells from imprinted fish showed increased sensitivity to phenyl ethyl alcohol compared either to cells from naive fish or to sensitivity to another behaviorally important odorant (L-serine). Field experiments verified an increased behavioral preference for phenyl ethyl alcohol by imprinted salmon as adults. Thus, some component of the imprinted olfactory homestream memory appears to be retained peripherally.

  7. Increased dopaminergic signaling impairs aversive olfactory memory retention in Drosophila.

    Science.gov (United States)

    Zhang, Shixing; Yin, Yan; Lu, Huimin; Guo, Aike

    2008-05-23

    Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.

  8. Effect of flumethrin on survival and olfactory learning in honeybees.

    Directory of Open Access Journals (Sweden)

    Ken Tan

    Full Text Available Flumethrin has been widely used as an acaricide for the control of Varroa mites in commercial honeybee keeping throughout the world for many years. Here we test the mortality of the Asian honeybee Apis cerana cerana after treatment with flumethrin. We also ask (1 how bees react to the odor of flumethrin, (2 whether its odor induces an innate avoidance response, (3 whether its taste transmits an aversive reinforcing component in olfactory learning, and (4 whether its odor or taste can be associated with reward in classical conditioning. Our results show that flumethrin has a negative effect on Apis ceranàs lifespan, induces an innate avoidance response, acts as a punishing reinforcer in olfactory learning, and interferes with the association of an appetitive conditioned stimulus. Furthermore flumethrin uptake within the colony reduces olfactory learning over an extended period of time.

  9. Atypical olfactory groove meningioma associated with uterine fibromatosis; case report

    Directory of Open Access Journals (Sweden)

    Toma I. Papacocea

    2016-11-01

    Full Text Available The concomitant presence of the olfactory groove meningioma with uterine fibrosis is very rare. Our report presents the case of a giant olfactory groove meningioma revealed after a uterine fibroma resection in a 44 years-old female, due to a generalized seizure 10 days after operation. Cranial CT-scan identified the tumor as an olfactory groove meningioma. The tumor was operated with a macroscopically complete resection; the endothermal coagulation of the dura attachment was performed (Simpson II with a good postoperative evolution. Laboratory results showed the presence of receptors for steroid hormones both in meningioma and uterine tumor, and the histopathological examination revealed an atypical meningioma with 17% proliferation markers. Our findings suggest that even though meningiomas are benign tumors and a complete resection usually indicates a good prognosis, the association with uterine fibromatosis and the presence of high percentage of steroid receptors creates a higher risk to relapse, imposing therefore a good monitoring.

  10. Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans.

    Science.gov (United States)

    Zhang, Yun; Lu, Hang; Bargmann, Cornelia I

    2005-11-10

    Food can be hazardous, either through toxicity or through bacterial infections that follow the ingestion of a tainted food source. Because learning about food quality enhances survival, one of the most robust forms of olfactory learning is conditioned avoidance of tastes associated with visceral malaise. The nematode Caenorhabditis elegans feeds on bacteria but is susceptible to infection by pathogenic bacteria in its natural environment. Here we show that C. elegans modifies its olfactory preferences after exposure to pathogenic bacteria, avoiding odours from the pathogen and increasing its attraction to odours from familiar nonpathogenic bacteria. Particular bacteria elicit specific changes in olfactory preferences that are suggestive of associative learning. Exposure to pathogenic bacteria increases serotonin in ADF chemosensory neurons by transcriptional and post-transcriptional mechanisms. Serotonin functions through MOD-1, a serotonin-gated chloride channel expressed in sensory interneurons, to promote aversive learning. An increase in serotonin may represent the negative reinforcing stimulus in pathogenic infection.

  11. Behavioural responses to olfactory cues in carrion crows.

    Science.gov (United States)

    Wascher, Claudia A F; Heiss, Rebecca S; Baglione, Vittorio; Canestrari, Daniela

    2015-02-01

    Until recently, the use of olfactory signals in birds has been largely ignored, despite the fact that birds do possess a fully functioning olfactory system and have been shown to use odours in social and foraging tasks, predator detection and orientation. The present study investigates whether carrion crows (Corvus corone corone), a bird species living in complex social societies, respond behaviourally to olfactory cues of conspecifics. During our experiment, carrion crows were observed less often close to the conspecific scent compared to a control side. Because conspecific scent was extracted during handling, a stressful procedure for birds, we interpreted the general avoidance of the 'scent' side as disfavour against a stressed conspecific. However, males, unlike females, showed less avoidance towards the scent of a familiar individual compared to an unfamiliar one, which might reflect a stronger interest in the information conveyed and/or willingness to provide social support. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Processing of Sensory Information in the Olfactory System

    DEFF Research Database (Denmark)

    The olfactory system is an attractive model system due to the easy control of sensory input and the experimental accessibility in animal studies. The odorant signals are processed from receptor neurons to a neural network of mitral and granular cells while various types of nonlinear behaviour can...... and equation-free techniques allow for a better reproduction and understanding of recent experimental findings. Talks: Olfaction as a Model System for Sensory-Processing Neural Networks (Jens Midtgaard, University of Copenhagen, Denmark) Nonlinear Effects of Signal Transduction in Olfactory Sensory Neurons......, Bayer Technology Services) Axonal Pathfinding and Sorting in the Olfactory System (Noemi Hummel, ETH Zuerich, Switzerland; Simon Kokkendorff and Jens Starke, Technical University of Denmark, Denmark) Analysis of Macroscopic Network Activities (Jens Starke, Technical University of Denmark, Denmark...

  13. Olfactory interference during inhibitory backward pairing in honey bees.

    Directory of Open Access Journals (Sweden)

    Matthieu Dacher

    Full Text Available Restrained worker honey bees are a valuable model for studying the behavioral and neural bases of olfactory plasticity. The proboscis extension response (PER; the proboscis is the mouthpart of honey bees is released in response to sucrose stimulation. If sucrose stimulation is preceded one or a few times by an odor (forward pairing, the bee will form a memory for this association, and subsequent presentations of the odor alone are sufficient to elicit the PER. However, backward pairing between the two stimuli (sucrose, then odor has not been studied to any great extent in bees, although the vertebrate literature indicates that it elicits a form of inhibitory plasticity.If hungry bees are fed with sucrose, they will release a long lasting PER; however, this PER can be interrupted if an odor is presented 15 seconds (but not 7 or 30 seconds after the sucrose (backward pairing. We refer to this previously unreported process as olfactory interference. Bees receiving this 15 second backward pairing show reduced performance after a subsequent single forward pairing (excitatory conditioning trial. Analysis of the results supported a relationship between olfactory interference and a form of backward pairing-induced inhibitory learning/memory. Injecting the drug cimetidine into the deutocerebrum impaired olfactory interference.Olfactory interference depends on the associative link between odor and PER, rather than between odor and sucrose. Furthermore, pairing an odor with sucrose can lead either to association of this odor to PER or to the inhibition of PER by this odor. Olfactory interference may provide insight into processes that gate how excitatory and inhibitory memories for odor-PER associations are formed.

  14. Olfactory modulation of affective touch processing - A neurophysiological investigation.

    Science.gov (United States)

    Croy, Ilona; Drechsler, Edda; Hamilton, Paul; Hummel, Thomas; Olausson, Håkan

    2016-07-15

    Touch can be highly emotional, and depending on the environment, it can be perceived as pleasant and comforting or disgusting and dangerous. Here, we studied the impact of context on the processing of tactile stimuli using a functional magnetic resonance imaging (fMRI) paradigm. This was achieved by embedding tactile stimulation in a variable olfactory environment. Twenty people were scanned with BOLD fMRI while receiving the following stimulus blocks: Slow stroking Touch, Civette odor (feces like), Rose odor, Touch+Civette, and Touch+Rose. Ratings of pleasantness and intensity of tactile stimuli and ratings of disgust and intensity of olfactory stimuli were collected. The impact of the olfactory context on the processing of touch was studied using covariance analyses. Coupling between olfactory processing and somatosensory processing areas was assessed with psychophysiological interaction analysis (PPI). A subjectively disgusting olfactory environment significantly reduced the perceived pleasantness of touch. The touch fMRI activation in the secondary somatosensory cortex, operculum 1 (OP1), was positively correlated with the disgust towards the odors. Decreased pleasantness of touch was related to decreased posterior insula activity. PPI analysis revealed a significant interaction between the OP1, posterior insula, and regions processing the disgust of odors (orbitofrontal cortex and amygdala). We conclude that the disgust evaluation of the olfactory environment moderates neural reactivity in somatosensory regions by upregulation of the OP1 and downregulation of the posterior insula. This adaptive regulation of affective touch processing may facilitate adaptive reaction to a potentially harmful stimulus. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The role of dopamine in Drosophila larval classical olfactory conditioning.

    Directory of Open Access Journals (Sweden)

    Mareike Selcho

    Full Text Available Learning and memory is not an attribute of higher animals. Even Drosophila larvae are able to form and recall an association of a given odor with an aversive or appetitive gustatory reinforcer. As the Drosophila larva has turned into a particularly simple model for studying odor processing, a detailed neuronal and functional map of the olfactory pathway is available up to the third order neurons in the mushroom bodies. At this point, a convergence of olfactory processing and gustatory reinforcement is suggested to underlie associative memory formation. The dopaminergic system was shown to be involved in mammalian and insect olfactory conditioning. To analyze the anatomy and function of the larval dopaminergic system, we first characterize dopaminergic neurons immunohistochemically up to the single cell level and subsequent test for the effects of distortions in the dopamine system upon aversive (odor-salt as well as appetitive (odor-sugar associative learning. Single cell analysis suggests that dopaminergic neurons do not directly connect gustatory input in the larval suboesophageal ganglion to olfactory information in the mushroom bodies. However, a number of dopaminergic neurons innervate different regions of the brain, including protocerebra, mushroom bodies and suboesophageal ganglion. We found that dopamine receptors are highly enriched in the mushroom bodies and that aversive and appetitive olfactory learning is strongly impaired in dopamine receptor mutants. Genetically interfering with dopaminergic signaling supports this finding, although our data do not exclude on naïve odor and sugar preferences of the larvae. Our data suggest that dopaminergic neurons provide input to different brain regions including protocerebra, suboesophageal ganglion and mushroom bodies by more than one route. We therefore propose that different types of dopaminergic neurons might be involved in different types of signaling necessary for aversive and appetitive

  16. Functional MRI of the olfactory system in conscious dogs.

    Directory of Open Access Journals (Sweden)

    Hao Jia

    Full Text Available We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology.

  17. Functional MRI of the Olfactory System in Conscious Dogs

    Science.gov (United States)

    Jia, Hao; Pustovyy, Oleg M.; Waggoner, Paul; Beyers, Ronald J.; Schumacher, John; Wildey, Chester; Barrett, Jay; Morrison, Edward; Salibi, Nouha; Denney, Thomas S.; Vodyanoy, Vitaly J.; Deshpande, Gopikrishna

    2014-01-01

    We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology. PMID:24466054

  18. Downregulation of CREB expression in Alzheimer's brain and in Aβ-treated rat hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Pham Serena

    2011-08-01

    Full Text Available Abstract Background Oxidative stress plays an important role in neuronal dysfunction and neuron loss in Alzheimer's brain. Previous studies have reported downregulation of CREB-mediated transcription by oxidative stress and Aβ. The promoter for CREB itself contains cyclic AMP response elements. Therefore, we examined the expression of CREB in the hippocampal neurons of Tg2576 mice, AD post-mortem brain and in cultured rat hippocampal neurons exposed to Aβ aggregates. Results Laser Capture Microdissection of hippocampal neurons from Tg2576 mouse brain revealed decreases in the mRNA levels of CREB and its target, BDNF. Immunohistochemical analysis of Tg2576 mouse brain showed decreases in CREB levels in hippocampus and cortex. Markers of oxidative stress were detected in transgenic mouse brain and decreased CREB staining was observed in regions showing abundance of astrocytes. There was also an inverse correlation between SDS-extracted Aβ and CREB protein levels in Alzheimer's post-mortem hippocampal samples. The levels of CREB-regulated BDNF and BIRC3, a caspase inhibitor, decreased and the active cleaved form of caspase-9, a marker for the intrinsic pathway of apoptosis, was elevated in these samples. Exposure of rat primary hippocampal neurons to Aβ fibrils decreased CREB promoter activity. Decrease in CREB mRNA levels in Aβ-treated neurons was reversed by the antioxidant, N-acetyl cysteine. Overexpression of CREB by adenoviral transduction led to significant protection against Aβ-induced neuronal apoptosis. Conclusions Our findings suggest that chronic downregulation of CREB-mediated transcription results in decrease of CREB content in the hippocampal neurons of AD brain which may contribute to exacerbation of disease progression.

  19. Cortical plasticity and olfactory function in early blindness.

    Directory of Open Access Journals (Sweden)

    Rodrigo Araneda

    2016-08-01

    Full Text Available Over the last decade, functional brain imaging has provided insight in the maturation processes and has helped elucidate the pathophysiological mechanisms involved in brain plasticity in the absence of vision. In case of congenital blindness, drastic changes occur within the deafferented visual cortex that starts receiving and processing nonvisual inputs, including olfactory stimuli. This functional reorganization of the occipital cortex gives rise to compensatory perceptual and cognitive mechanisms that help blind persons to achieve perceptual tasks, leading to superior olfactory abilities in these subjects. This view receives support from psychophysical testing, volumetric measurements and functional brain imaging studies in humans, which are presented here.

  20. Nuclear architecture and gene silencing in olfactory sensory neurons.

    Science.gov (United States)

    Armelin-Correa, Lucia M; Nagai, Maíra H; Leme Silva, Artur G; Malnic, Bettina

    2014-01-01

    Odorants are discriminated by hundreds of odorant receptor (OR) genes, which are dispersed throughout the mammalian genome. The OR genes are expressed in a highly specialized type of cell, the olfactory sensory neuron. Each one of these neurons expresses one of the 2 alleles from one single OR gene type. The mechanisms underlying OR gene expression are unclear. Here we describe recent work demonstrating that the olfactory sensory neuron shows a particular nuclear architecture, and that the genomic OR loci are colocalized in silencing heterochromatin compartments within the nucleus. These discoveries highlight the important role played by epigenetic modifications and nuclear genome organization in the regulation of OR gene expression.

  1. Prominent facilitation at beta and gamma frequency range revealed with physiological calcium concentration in adult mouse piriform cortex in vitro.

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    Marie Gleizes

    Full Text Available Neuronal activity is characterized by a diversity of oscillatory phenomena that are associated with multiple behavioral and cognitive processes, yet the functional consequences of these oscillations are not fully understood. Our aim was to determine whether and how these different oscillatory activities affect short-term synaptic plasticity (STP, using the olfactory system as a model. In response to odorant stimuli, the olfactory bulb displays a slow breathing rhythm as well as beta and gamma oscillations. Since the firing of olfactory bulb projecting neurons is phase-locked with beta and gamma oscillations, structures downstream from the olfactory bulb should be driven preferentially at these frequencies. We examined STP exhibited by olfactory bulb inputs in slices of adult mouse piriform cortex maintained in vitro in an in vivo-like ACSF (calcium concentration: 1.1 mM. We replaced the presynaptic neuronal firing rate by repeated electrical stimulation (frequency between 3.125 and 100 Hz applied to the lateral olfactory tract. Our results revealed a considerable enhancement of postsynaptic response amplitude for stimulation frequencies in the beta and gamma range. A phenomenological model of STP fitted to the data suggests that the experimental results can be explained by the interplay between three mechanisms: a short-term facilitation mechanism (time constant ≈160 msec, and two short-term depression mechanisms (recovery time constants <20 msec and ≈140 msec. Increasing calcium concentration (2.2 mM resulted in an increase in the time constant of facilitation and in a strengthening of the slowest depression mechanism. As a result, response enhancement was reduced and its peak shifted toward the low beta and alpha ranges while depression became predominant in the gamma band. Using environmental conditions corresponding to those that prevail in vivo, our study shows that STP in the lateral olfactory tract to layer Ia synapse allows

  2. Hippocampal CA1 local field potential oscillations induced by olfactory cue of liked food.

    Science.gov (United States)

    Samerphob, Nifareeda; Cheaha, Dania; Chatpun, Surapong; Kumarnsit, Ekkasit

    2017-07-01

    Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant α-synuclein.

    Science.gov (United States)

    Zhang, Sufang; Xiao, Qian; Le, Weidong

    2015-01-01

    Parkinson disease is a multi-system neurodegenerative disease characterized by both motor and non-motor symptoms. Hyposmia is one of the early non-motor symptoms occurring in more than 90% of Parkinson disease cases, which can precede motor symptoms even several years. Up to now, the relationship between hyposmia and Parkinson disease remains elusive. Lack of proper animal models of hyposmia restricts the investigation. In this study we assessed olfactory function in Prp-A53T-α-synuclein transgenic (αSynA53T) mice which had been reported to show age-dependent motor impairments and intracytoplasmic inclusions. We also examined cholinergic and dopaminergic systems in olfactory bulb of αSynA53T mice by immunofluorescent staining, enzyme linked immunosorbent assay and western blot. We found that compared to wild type littermates, αSynA53T mice at 6 months or older displayed a deficit of odor discrimination and odor detection. No significant changes were found in olfactory memory and odor habituation. Furthermore compared to wildtype littermates, in olfactory bulb of αSynA53T mice at 10 months old we detected a marked decrease of cholinergic neurons in mitral cell layer and a decrease of acetylcholinesterase activity, while dopaminergic neurons were found increased in glomerular layer, accompanied with an increase of tyrosine hydroxylase protein. Our studies indicate that αSynA53T mice have olfactory dysfunction before motor deficits occur, and the cholinergic and dopaminergic disturbance might be responsible for the Parkinson disease-related olfactory dysfunction.

  4. Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant α-synuclein.

    Directory of Open Access Journals (Sweden)

    Sufang Zhang

    Full Text Available Parkinson disease is a multi-system neurodegenerative disease characterized by both motor and non-motor symptoms. Hyposmia is one of the early non-motor symptoms occurring in more than 90% of Parkinson disease cases, which can precede motor symptoms even several years. Up to now, the relationship between hyposmia and Parkinson disease remains elusive. Lack of proper animal models of hyposmia restricts the investigation. In this study we assessed olfactory function in Prp-A53T-α-synuclein transgenic (αSynA53T mice which had been reported to show age-dependent motor impairments and intracytoplasmic inclusions. We also examined cholinergic and dopaminergic systems in olfactory bulb of αSynA53T mice by immunofluorescent staining, enzyme linked immunosorbent assay and western blot. We found that compared to wild type littermates, αSynA53T mice at 6 months or older displayed a deficit of odor discrimination and odor detection. No significant changes were found in olfactory memory and odor habituation. Furthermore compared to wildtype littermates, in olfactory bulb of αSynA53T mice at 10 months old we detected a marked decrease of cholinergic neurons in mitral cell layer and a decrease of acetylcholinesterase activity, while dopaminergic neurons were found increased in glomerular layer, accompanied with an increase of tyrosine hydroxylase protein. Our studies indicate that αSynA53T mice have olfactory dysfunction before motor deficits occur, and the cholinergic and dopaminergic disturbance might be responsible for the Parkinson disease-related olfactory dysfunction.

  5. The mannose receptor is expressed by olfactory ensheathing cells in the rat olfactory bulb.

    Science.gov (United States)

    Carvalho, Litia A; Nobrega, Alberto F; Soares, Igor D P; Carvalho, Sergio L; Allodi, Silvana; Baetas-da-Cruz, Wagner; Cavalcante, Leny A

    2013-12-01

    Complex carbohydrate structures are essential molecules of infectious bacteria, parasites, and host cells and are involved in cell signaling associated with immune responses, glycoprotein homeostasis, and cell migration. The uptake of mannose-tailed glycans is usually carried out by professional phagocytes to trigger MHC class I- and MHC class II-restricted antigen presentation or, alternatively, to end inflammation. We have detected the mannose receptor (MR) in cultured olfactory ensheathing cells (OECs), so we investigated by flow cytometry whether recently dissociated cells of the olfactory bulb (OB) nerve fiber layer (ONL) could bind a mannosylated ligand (fluorescein conjugate of mannosyl bovine serum albumin; Man/BSA-FITC) in a specific manner. In addition, we estimated the relative proportion of ONL OECs, microglia, and astrocytes, tagged by 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), by the B4 isolectin of Griffonia simplicifonia (IB4), and by glial fibrillary acidic protein (GFAP), respectively, that were Man/BSA-FITC(+) . We also determined by histochemistry and/or immunohistochemistry whether Man/BSA-FITC or an anti-MR antibody (anti-C-terminal MR peptide; anti-cMR) labeled OECs and/or parenchymal microglia. In addition, we confirmed by Western blot with the K1K2 (against the entire MR molecule) antibody that a band of about 180 kDA is expressed in the OB. Our findings are compatible with a prospective sentinel role of OECs against pathogens of the upper airways and/or damage-associated glycidic patterns as well as with homeostasis of OB mannosylated glycoproteins. Copyright © 2013 Wiley Periodicals, Inc.

  6. Consolidation of an olfactory memory trace in the olfactory bulb is required for learning-induced survival of adult-born neurons and long-term memory.

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    Florence Kermen

    Full Text Available BACKGROUND: It has recently been proposed that adult-born neurons in the olfactory bulb, whose survival is modulated by learning, support long-term olfactory memory. However, the mechanism used to select which adult-born neurons following learning will participate in the long-term retention of olfactory information is unknown. We addressed this question by investigating the effect of bulbar consolidation of olfactory learning on memory and neurogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we used a behavioral ecological approach using adult mice to assess the impact of consolidation on neurogenesis. Using learning paradigms in which consolidation time was varied, we showed that a spaced (across days, but not a massed (within day, learning paradigm increased survival of adult-born neurons and allowed long-term retention of the task. Subsequently, we used a pharmacological approach to block consolidation in the olfactory bulb, consisting in intrabulbar infusion of the protein synthesis inhibitor anisomycin, and found impaired learning and no increase in neurogenesis, while basic olfactory processing and the basal rate of adult-born neuron survival remained unaffected. Taken together these data indicate that survival of adult-born neurons during learning depends on consolidation processes taking place in the olfactory bulb. CONCLUSION/SIGNIFICANCE: We can thus propose a model in which consolidation processes in the olfactory bulb determine both survival of adult-born neurons and long-term olfactory memory. The finding that adult-born neuron survival during olfactory learning is governed by consolidation in the olfactory bulb strongly argues in favor of a role for bulbar adult-born neurons in supporting olfactory memory.

  7. What is the short term effect of perfumes on olfactory thresholds?

    Science.gov (United States)

    Robinson, A M; Gaskin, J A; Philpott, C M; Goodenough, P C; Elloy, M; Clark, A; Murty, G E

    2007-08-01

    Body sprays and perfumes are commonly worn by patients attending ENT out-patients clinics. Their effect on performance in olfactory testing is unknown. The aim of this study was to determine whether olfactory thresholds are altered by the presence of such fragrances. One hundred and sixty healthy volunteers, aged 18 to 65 years, underwent olfactory thresholds testing. Each was then exposed to one of four strong perfumes, applied in a facemask for two minutes, and the thresholds were retested. All olfactory thresholds worsened after being exposed to the strong perfumes of Lynx and Impulse body sprays, with the strongest effect being on olfactory detection of phenylethyl alcohol (pperfumes can have a negative effect on olfactory thresholds. Patients attending olfactory threshold testing need to be advised not to wear body sprays or perfumes.

  8. Nonoccupational environmental exposure to manganese is linked to deficits in peripheral and central olfactory function.

    Science.gov (United States)

    Guarneros, Marco; Ortiz-Romo, Nahum; Alcaraz-Zubeldia, Mireya; Drucker-Colín, René; Hudson, Robyn

    2013-11-01

    Manganese is of growing concern as a toxic air pollutant. It is readily transported from the olfactory epithelium to the olfactory bulb, and unlike other metals, it is transported transynaptically to structures deep within the brain. However, little is known regarding the possible effect of nonoccupational exposure to manganese on olfactory function. Using the Sniffin' Sticks test battery, we compared the olfactory performance of subjects from a manganese mining district living central effects on olfactory function of big city air pollution, which mostly consists of toxicants known to affect the olfactory epithelium but with lower transynaptic transport capacity compared with manganese. We conclude that nonoccupational exposure to airborne manganese is associated with decrements in both peripheral and central olfactory function.

  9. Newborn neurons in the olfactory bulb selected for long-term survival through olfactory learning are prematurely suppressed when the olfactory memory is erased.

    Science.gov (United States)

    Sultan, Sébastien; Rey, Nolwen; Sacquet, Joelle; Mandairon, Nathalie; Didier, Anne

    2011-10-19

    A role for newborn neurons in olfactory memory has been proposed based on learning-dependent modulation of olfactory bulb neurogenesis in adults. We hypothesized that if newborn neurons support memory, then they should be suppressed by memory erasure. Using an ecological approach in mice, we showed that behaviorally breaking a previously learned odor-reward association prematurely suppressed newborn neurons selected to survive during initial learning. Furthermore, intrabulbar infusions of the caspase pan-inhibitor ZVAD (benzyloxycarbonyl-Val-Ala-Asp) during the behavioral odor-reward extinction prevented newborn neurons death and erasure of the odor-reward association. Newborn neurons thus contribute to the bulbar network plasticity underlying long-term memory.

  10. Signal processing inspired from the olfactory bulb for electronic noses

    Science.gov (United States)

    Jing, Ya-Qi; Meng, Qing-Hao; Qi, Pei-Feng; Zeng, Ming; Liu, Ying-Jie

    2017-01-01

    A bio-inspired signal processing method is proposed for electronic noses (e-noses). The proposed method contains an olfactory bulb model and a feature generation step. The structure of the olfactory bulb model is similar to the anatomical structure of mammals’ olfactory bulb. It consists of olfactory receptor neurons, mitral cells, granule cells, periglomerular cells, and short axon cells. This model uses gas sensors’ original response curves and transforms them to neuron spiking series no matter what kind the response curve is. This largely simplifies the follow-up feature generation step. Recurrence quantification analysis is employed to perform feature generation and the five most important features are selected. Finally, in order to verify the performance of the proposed method, seven kinds of Chinese liquors are tested and three classification methods are used to classify them. The experimental results demonstrate that the proposed method has a higher classification rate (99.05%) and also a steadier performance with the change of sensor number and types than the classic one.

  11. Designing exons for human olfactory receptor gene subfamilies ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 35; Issue 3. Designing exons for human olfactory receptor gene subfamilies using a mathematical paradigm. Sk Sarif Hassan Pabitra Pal Choudhury Amita Pal R L Brahmachary Arunava Goswami. Articles Volume 35 Issue 3 September 2010 pp 389-393 ...

  12. The Effect of External Approach Septoplasty on Olfactory Function.

    Science.gov (United States)

    Türk, Bilge; Akpinar, Meltem; Altundağ, Aytuğ; Kirik, Mehtap Özkahraman; Ünsal, Özlem; Coşkun, Berna Uslu

    2017-10-01

    Septal deviation-induced nasal obstruction is frequently accompanied by hyposmia. The aim of this study was to evaluate the effect of external approach septoplasty on olfactory function. Thirty patients (23 males, 7 females) who had external approach septoplasty were included in the study. The age interval was 18 to 60 years (mean 33±12 years). All subjects had olfactory function and acoustic rhinometry tests in both the pre- and postoperative periods (mean interval 6 weeks ± 3 weeks). Olfactory function was determined by the "Sniffin Sticks" test. The minimum cross-sectional area from the nostril to 2.20 cm backward was referred to as MCA1, and the minimum cross-sectional area from 2.20 to 5.40 cm was referred to as MCA2, determined by acoustic rhinometry. Olfactory threshold, discrimination, and identification function improved significantly after external approach septoplasty. A statistically significant difference was also detected between pre- and postoperative left MCA1 and left MCA2 of the nasal cavities. Postoperative hyposmic and anosmic patient improvement was statistically significant. External approach septoplasty has a beneficial effect on olfaction and this effect may be partly due to interactions between the increased perception of nasal air flow, as well as surgery-associated improvement in the internal nasal valve area.

  13. A Robust Feedforward Model of the Olfactory System.

    Directory of Open Access Journals (Sweden)

    Yilun Zhang

    2016-04-01

    Full Text Available Most natural odors have sparse molecular composition. This makes the principles of compressed sensing potentially relevant to the structure of the olfactory code. Yet, the largely feedforward organization of the olfactory system precludes reconstruction using standard compressed sensing algorithms. To resolve this problem, recent theoretical work has shown that signal reconstruction could take place as a result of a low dimensional dynamical system converging to one of its attractor states. However, the dynamical aspects of optimization slowed down odor recognition and were also found to be susceptible to noise. Here we describe a feedforward model of the olfactory system that achieves both strong compression and fast reconstruction that is also robust to noise. A key feature of the proposed model is a specific relationship between how odors are represented at the glomeruli stage, which corresponds to a compression, and the connections from glomeruli to third-order neurons (neurons in the olfactory cortex of vertebrates or Kenyon cells in the mushroom body of insects, which in the model corresponds to reconstruction. We show that should this specific relationship hold true, the reconstruction will be both fast and robust to noise, and in particular to the false activation of glomeruli. The predicted connectivity rate from glomeruli to third-order neurons can be tested experimentally.

  14. SnapShot: Olfactory Classical Conditioning of Drosophila.

    Science.gov (United States)

    Davis, Ronald L

    2015-10-08

    This SnapShot summarizes current knowledge about the molecules and circuitry that mediate olfactory memory formation in Drosophila, with emphasis on neural circuits carrying the learned sensory information; the molecular mechanisms for acquisition, memory storage, and forgetting; and the output pathways for memory expression. To view this SnapShot, open or download the PDF. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Odor memory stability after reinnervation of the olfactory bulb.

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    Eduardo Blanco-Hernández

    Full Text Available The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP. Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain.

  16. Olfactory memories are intensity specific in larval Drosophila.

    Science.gov (United States)

    Mishra, Dushyant; Chen, Yi-Chun; Yarali, Ayse; Oguz, Tuba; Gerber, Bertram

    2013-05-01

    Learning can rely on stimulus quality, stimulus intensity, or a combination of these. Regarding olfaction, the coding of odour quality is often proposed to be combinatorial along the olfactory pathway, and working hypotheses are available concerning short-term associative memory trace formation of odour quality. However, it is less clear how odour intensity is coded, and whether olfactory memory traces include information about the intensity of the learnt odour. Using odour-sugar associative conditioning in larval Drosophila, we first describe the dose-effect curves of learnability across odour intensities for four different odours (n-amyl acetate, 3-octanol, 1-octen-3-ol and benzaldehyde). We then chose odour intensities such that larvae were trained at an intermediate odour intensity, but were tested for retention with either that trained intermediate odour intensity, or with respectively higher or lower intensities. We observed a specificity of retention for the trained intensity for all four odours used. This adds to the appreciation of the richness in 'content' of olfactory short-term memory traces, even in a system as simple as larval Drosophila, and to define the demands on computational models of associative olfactory memory trace formation. We suggest two kinds of circuit architecture that have the potential to accommodate intensity learning, and discuss how they may be implemented in the insect brain.

  17. Distinct Neural Mechanisms Mediate Olfactory Memory Formation at Different Timescales

    Science.gov (United States)

    McNamara, Ann Marie; Magidson, Phillip D.; Linster, Christiane; Wilson, Donald A.; Cleland, Thomas A.

    2008-01-01

    Habituation is one of the oldest forms of learning, broadly expressed across sensory systems and taxa. Here, we demonstrate that olfactory habituation induced at different timescales (comprising different odor exposure and intertrial interval durations) is mediated by different neural mechanisms. First, the persistence of habituation memory is…

  18. Olfactory Imagination and Odor Processing: Three Same-Different Experiments

    NARCIS (Netherlands)

    Koster, E.P.; Stelt, van der O.; Nixdorf, R.R.; Linschoten, M.R.I.; Mojet, J.; Wijk, de R.A.

    2014-01-01

    Do people who claim to have olfactory imagination process odors more efficiently? In three same–different experiments, using all possible combinations of odors and odor names as primes and targets, selected high imagers (n¿=¿12) were faster (±230 ms; P¿

  19. Virtual vision system with actual flavor by olfactory display

    Science.gov (United States)

    Sakamoto, Kunio; Kanazawa, Fumihiro

    2010-11-01

    The authors have researched multimedia system and support system for nursing studies on and practices of reminiscence therapy and life review therapy. The concept of the life review is presented by Butler in 1963. The process of thinking back on one's life and communicating about one's life to another person is called life review. There is a famous episode concerning the memory. It is called as Proustian effects. This effect is mentioned on the Proust's novel as an episode that a story teller reminds his old memory when he dipped a madeleine in tea. So many scientists research why smells trigger the memory. The authors pay attention to the relation between smells and memory although the reason is not evident yet. Then we have tried to add an olfactory display to the multimedia system so that the smells become a trigger of reminding buried memories. An olfactory display is a device that delivers smells to the nose. It provides us with special effects, for example to emit smell as if you were there or to give a trigger for reminding us of memories. The authors have developed a tabletop display system connected with the olfactory display. For delivering a flavor to user's nose, the system needs to recognition and measure positions of user's face and nose. In this paper, the authors describe an olfactory display which enables to detect the nose position for an effective delivery.

  20. Olfactory-Induced Synesthesias: A Review and Model

    Science.gov (United States)

    Stevenson, Richard J.; Tomiczek, Caroline

    2007-01-01

    Recent reviews of synesthesia concentrate upon rare neurodevelopmental examples and exclude common olfactory-induced experiences with which they may profitably be compared. Like the neurodevelopmental synesthesias, odor-induced experiences involve different sensory modalities; are reliable, asymmetric (concurrents cannot induce), and automatic;…

  1. Development of olfactory ability in children: sensitivity and identification.

    Science.gov (United States)

    Monnery-Patris, S; Rouby, C; Nicklaus, S; Issanchou, S

    2009-04-01

    This study assessed the influence of school level and gender on odor sensitivity and identification, and the role of verbal capacity on odor identification in children (4-12 years) by using a revised version of an olfactory test designed for adults [Rouby et al. (1997). Connaissance et reconnaissance d'une série olfactive chez l'enfant préscolaire. Enfance, 1, 152-171]. We found that odor sensitivity and identification scores increased with school level, and that identification performance was better in girls than in boys. However, when we controlled verbal ability, the gender differences disappeared and the school level differences remained. This result indicates that the effect of gender on identification was probably due to the greater verbal ability of girls rather than to their greater olfactory ability per se. In addition, we found that general verbal ability is independent of olfactory fluency and that their influence on olfactory perception is different. Thus, this study illuminates the role of cognitive/verbal factors in the development of odor perception and knowledge. (c) 2009 Wiley Periodicals, Inc.

  2. Olfactory-visual integration facilitates perception of subthreshold negative emotion.

    Science.gov (United States)

    Novak, Lucas R; Gitelman, Darren R; Schuyler, Brianna; Li, Wen

    2015-10-01

    A fast growing literature of multisensory emotion integration notwithstanding, the chemical senses, intimately associated with emotion, have been largely overlooked. Moreover, an ecologically highly relevant principle of "inverse effectiveness", rendering maximal integration efficacy with impoverished sensory input, remains to be assessed in emotion integration. Presenting minute, subthreshold negative (vs. neutral) cues in faces and odors, we demonstrated olfactory-visual emotion integration in improved emotion detection (especially among individuals with weaker perception of unimodal negative cues) and response enhancement in the amygdala. Moreover, while perceptual gain for visual negative emotion involved the posterior superior temporal sulcus/pSTS, perceptual gain for olfactory negative emotion engaged both the associative olfactory (orbitofrontal) cortex and amygdala. Dynamic causal modeling (DCM) analysis of fMRI timeseries further revealed connectivity strengthening among these areas during crossmodal emotion integration. That multisensory (but not low-level unisensory) areas exhibited both enhanced response and region-to-region coupling favors a top-down (vs. bottom-up) account for olfactory-visual emotion integration. Current findings thus confirm the involvement of multisensory convergence areas, while highlighting unique characteristics of olfaction-related integration. Furthermore, successful crossmodal binding of subthreshold aversive cues not only supports the principle of "inverse effectiveness" in emotion integration but also accentuates the automatic, unconscious quality of crossmodal emotion synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The role of main olfactory and vomeronasal systems in animal ...

    African Journals Online (AJOL)

    The olfactory and vomeronasal systems have overlapping functions and both are involved in responses to both pheromones and chemical odorants. Several studies in insects, amphibians rodents and ungulates have established the importance of pheromones in the astonishing influence exerted by the male on the ...

  4. Olfactory attractiveness of mixtures of some host plant and ...

    African Journals Online (AJOL)

    A simple "Y" shaped olfactometer was used in laboratory studies on the olfactory attractiveness of mixtures in various proportions of industrial analogues of some host plant and conspecific-based semiochemicals, or their combinations with banana rhizome, to the banana weevil. The aim was to identify factors that influence ...

  5. Mechanisms of permanent loss of olfactory receptor neurons induced by the herbicide 2,6-dichlorobenzonitrile: Effects on stem cells and noninvolvement of acute induction of the inflammatory cytokine IL-6

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Fang; Fang, Cheng [Laboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); School of Public Health, State University of New York at Albany, NY 12201 (United States); Schnittke, Nikolai [Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Schwob, James E. [Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111 (United States); Ding, Xinxin, E-mail: xding@wadsworth.org [Laboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, Albany, NY 12201 (United States); School of Public Health, State University of New York at Albany, NY 12201 (United States)

    2013-11-01

    We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24 h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasal cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreEr{sup T2}::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. - Highlights: • The herbicide dichlobenil (DCBN) can damage olfactory epithelium stem cells. • Another olfactory toxicant, methimazole, leaves the olfactory stem cells intact. • DCBN, but not methimazole, induces a prolonged increase in nasal IL-6 levels. • Dexamethasone

  6. Adult neurogenesis restores dopaminergic neuronal loss in the olfactory bulb.

    Science.gov (United States)

    Lazarini, Françoise; Gabellec, Marie-Madeleine; Moigneu, Carine; de Chaumont, Fabrice; Olivo-Marin, Jean-Christophe; Lledo, Pierre-Marie

    2014-10-22

    Subventricular zone (SVZ) neurogenesis continuously provides new GABA- and dopamine (DA)-containing interneurons for the olfactory bulb (OB) in most adult mammals. DAergic interneurons are located in the glomerular layer (GL) where they participate in the processing of sensory inputs. To examine whether adult neurogenesis might contribute to regeneration after circuit injury in mice, we induce DAergic neuronal loss by injecting 6-hydroxydopamine (6-OHDA) in the dorsal GL or in the right substantia nigra pars compacta. We found that a 6-OHDA treatment of the OB produces olfactory deficits and local inflammation and partially decreases the number of neurons expressing the enzyme tyrosine hydroxylase (TH) near the injected site. Blockade of inflammation by minocycline treatment immediately after the 6-OHDA administration rescued neither TH(+) interneuron number nor the olfactory deficits, suggesting that the olfactory impairments are most likely linked to TH(+) cell death and not to microglial activation. TH(+) interneuron number was restored 1 month later. This rescue resulted at least in part from enhanced recruitment of immature neurons targeting the lesioned GL area. Seven days after 6-OHDA lesion in the OB, we found that the integration of lentivirus-labeled adult-born neurons was biased: newly formed neurons were preferentially incorporated into glomerular circuits of the lesioned area. Behavioral rehabilitation occurs 2 months after lesion. This study establishes a new model into which loss of DAergic cells could be compensated by recruiting newly formed neurons. We propose that adult neurogenesis not only replenishes the population of DAergic bulbar neurons but that it also restores olfactory sensory processing. Copyright © 2014 the authors 0270-6474/14/3414430-13$15.00/0.

  7. Effects of maternal immune activation on adult neurogenesis in the subventricular zone-olfactory bulb pathway and olfactory discrimination.

    Science.gov (United States)

    Liu, Yuan-Hsuan; Lai, Wen-Sung; Tsay, Huey-Jen; Wang, Tsu-Wei; Yu, Jenn-Yah

    2013-12-01

    Maternal infection and maternal immune activation (MIA) during pregnancy increase risks for psychiatric disorders such as schizophrenia and autism. Many deficits related to psychiatric disorders are observed in adult offspring of MIA animal models, including behavioral abnormalities, morphological defects in various brain regions, and dysregulation of neurotransmitter systems. It has previously been shown that MIA impairs adult neurogenesis in the dentate gyrus of the hippocampus. In this study, we examined whether MIA affects adult neurogenesis in the subventricular zone (SVZ)-olfactory bulb (OB) pathway. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic analog of double-stranded RNA mimicking viral infection, was injected into pregnant mice on gestation day 9.5 to activate immune systems. In the SVZ-OB pathway of adult offspring, different cell types of the neural stem cell lineage responded differently to MIA. Neural stem cells and neuroblasts were decreased. Cell proliferation of transit-amplifying cells was impaired. Consequently, newborn neurons were reduced in the OB. Olfactory deficiency has been suggested as a biomarker for schizophrenia. Here we found that olfactory discrimination was compromised in adult MIA offspring. Taken together, these findings show that MIA leads to defective adult neurogenesis in the SVZ-OB pathway, and the impairment of adult neurogenesis may lead to deficits in olfactory functions. © 2013.

  8. Regulation of spike timing-dependent plasticity of olfactory inputs in mitral cells in the rat olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Teng-Fei Ma

    Full Text Available The recent history of activity input onto granule cells (GCs in the main olfactory bulb can affect the strength of lateral inhibition, which functions to generate contrast enhancement. However, at the plasticity level, it is unknown whether and how the prior modification of lateral inhibition modulates the subsequent induction of long-lasting changes of the excitatory olfactory nerve (ON inputs to mitral cells (MCs. Here we found that the repetitive stimulation of two distinct excitatory inputs to the GCs induced a persistent modification of lateral inhibition in MCs in opposing directions. This bidirectional modification of inhibitory inputs differentially regulated the subsequent synaptic plasticity of the excitatory ON inputs to the MCs, which was induced by the repetitive pairing of excitatory postsynaptic potentials (EPSPs with postsynaptic bursts. The regulation of spike timing-dependent plasticity (STDP was achieved by the regulation of the inter-spike-interval (ISI of the postsynaptic bursts. This novel form of inhibition-dependent regulation of plasticity may contribute to the encoding or processing of olfactory information in the olfactory bulb.

  9. Oligomeric amyloid-β peptide disrupts olfactory information output by impairment of local inhibitory circuits in rat olfactory bulb.

    Science.gov (United States)

    Hu, Bin; Geng, Chi; Hou, Xiao-Yu

    2017-03-01

    Although early olfactory dysfunction has been found in patients with Alzheimer's disease, the underlying mechanisms remain unclear. In this study, we investigated whether and how oligomeric amyloid-β peptide (Aβ) affects the responses of mitral cells (MCs). We found that oligomeric Aβ1-42 increased spontaneous and evoked firing rates but decreased the ratio of evoked to spontaneous firings in MCs. Aβ1-42 oligomers showed no impact on the hyperactivity exerted by pharmacological blockage of GABAA receptors, suggesting an involvement of GABAergic inhibitory transmission in Aβ1 to 42-induced over-excitability. It was further determined that Aβ1-42 oligomers inhibited the frequency of spontaneous inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents, as well as the amplitude of miniature inhibitory postsynaptic currents in MCs. Both recurrent and lateral inhibition of MCs, which are critical for odor discrimination, were also disrupted by Aβ1-42 oligomers. The above data indicate that Aβ impairs local inhibitory circuits and thereby leads to perturbations of olfactory information output in the olfactory bulb. This study reveals a cellular and synaptic basis of olfactory deficits associated with Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Olfactory bulb glomerular NMDA receptors mediate olfactory nerve potentiation and odor preference learning in the neonate rat.

    Directory of Open Access Journals (Sweden)

    Rebecca Lethbridge

    Full Text Available Rat pup odor preference learning follows pairing of bulbar beta-adrenoceptor activation with olfactory input. We hypothesize that NMDA receptor (NMDAR-mediated olfactory input to mitral cells is enhanced during training, such that increased calcium facilitates and shapes the critical cAMP pattern. Here, we demonstrate, in vitro, that olfactory nerve stimulation, at sniffing frequencies, paired with beta-adrenoceptor activation, potentiates olfactory nerve-evoked mitral cell firing. This potentiation is blocked by a NMDAR antagonist and by increased inhibition. Glomerular disinhibition also induces NMDAR-sensitive potentiation. In vivo, in parallel, behavioral learning is prevented by glomerular infusion of an NMDAR antagonist or a GABA(A receptor agonist. A glomerular GABA(A receptor antagonist paired with odor can induce NMDAR-dependent learning. The NMDA GluN1 subunit is phosphorylated in odor-specific glomeruli within 5 min of training suggesting early activation, and enhanced calcium entry, during acquisition. The GluN1 subunit is down-regulated 3 h after learning; and at 24 h post-training the GluN2B subunit is down-regulated. These events may assist memory stability. Ex vivo experiments using bulbs from trained rat pups reveal an increase in the AMPA/NMDA EPSC ratio post-training, consistent with an increase in AMPA receptor insertion and/or the decrease in NMDAR subunits. These results support a model of a cAMP/NMDA interaction in generating rat pup odor preference learning.

  11. Chromatin Modulatory Proteins and Olfactory Receptor Signaling in the Refinement and Maintenance of Fruitless Expression in Olfactory Receptor Neurons.

    Directory of Open Access Journals (Sweden)

    Catherine E Hueston

    2016-04-01

    Full Text Available During development, sensory neurons must choose identities that allow them to detect specific signals and connect with appropriate target neurons. Ultimately, these sensory neurons will successfully integrate into appropriate neural circuits to generate defined motor outputs, or behavior. This integration requires a developmental coordination between the identity of the neuron and the identity of the circuit. The mechanisms that underlie this coordination are currently unknown. Here, we describe two modes of regulation that coordinate the sensory identities of Drosophila melanogaster olfactory receptor neurons (ORNs involved in sex-specific behaviors with the sex-specific behavioral circuit identity marker fruitless (fru. The first mode involves a developmental program that coordinately restricts to appropriate ORNs the expression of fru and two olfactory receptors (Or47b and Ir84a involved in sex-specific behaviors. This regulation requires the chromatin modulatory protein Alhambra (Alh. The second mode relies on the signaling from the olfactory receptors through CamK and histone acetyl transferase p300/CBP to maintain ORN-specific fru expression. Our results highlight two feed-forward regulatory mechanisms with both developmentally hardwired and olfactory receptor activity-dependent components that establish and maintain fru expression in ORNs. Such a dual mechanism of fru regulation in ORNs might be a trait of neurons driving plastic aspects of sex-specific behaviors.

  12. A Unifying Data-Driven Model of Human Olfactory Pathology Representing Known Etiologies of Dysfunction.

    Science.gov (United States)

    Lötsch, Jörn; Ultsch, Alfred; Hummel, Thomas

    2016-08-26

    In the clinical diagnosis of olfactory function, 2 quantitative extremes of either lost or normal olfactory function are in the focus while no particular attention is directed at the interval between the 2 main diagnoses of "anosmia" or "normosmia", respectively. We analyzed the modal distribution of olfactory scores with the intention to describe a complex human olfactory pathology in a unifying model. In a cross-sectional retrospective study, olfactory performance scores acquired from 10714 individuals by means of a clinically established psychophysical test were analyzed with respect to their modal distribution by fitting a Gaussian mixture model (GMM) to the data. The probability distribution of all olfactory scores was found to be multimodal. It could be described as a mixture of 6 Gaussian distributions at a high statistical significance level of P pathologies associated with the olfactory dysfunction could be shown to be reflected in 1-3 distinct Gaussians. This provides the possibility to assign distinct degrees of olfactory acuity with each etiology. Results indicate that human olfactory pathology is composed of clearly distinct subpathologies that can be connected with underlying subetiologies. We present a unifying data science-based model that satisfies the human olfactory pathology observed in 10714 subjects. The analysis of the distribution of their olfactory performance scores suggests a complex but very distinct human olfactory pathology. This implies a distinction of the olfactory diagnosis of hyposmia from those of anosmia or normosmia. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Enantioselective recognition of menthol by mouse odorant receptors.

    Science.gov (United States)

    Takai, Yoshiki; Touhara, Kazushige

    2015-01-01

    The olfactory system has a remarkable ability to detect and discriminate a vast variety of odorant molecules. In mammals, hundreds to thousands of odorant receptors (ORs) expressed in olfactory sensory neurons play an essential role in this discrimination. Odorants are recognized by ORs in a combinatorial fashion in which a single odorant activates a particular combination of receptors, leading to its perception as a particular aroma. It is well known that enantiomers emit different aromas in spite of exhibiting otherwise identical chemical properties. To elucidate the molecular basis for the difference, we recorded responses to l- and d-menthol in the mouse olfactory bulb and found that enantiomers elicited similar but overlapping and distinct receptor activation patterns. We then identified l-menthol-specific and d-menthol-biased receptors and performed detailed structure-activity relationship studies, revealing high stereoselectivity of the enantiospecific menthol receptor. The binding site on ORs appears to have evolved to distinguish subtle differences in very similar odorant structures.

  14. Transgenic expression of B-50/GAP-43 in mature olfactory neurons triggers downregulation of native B-50/GAP-43 expression in immature olfactory neurons

    NARCIS (Netherlands)

    Holtmaat, Anthony J D G; Huizinga, C T; Margolis, F L; Gispen, Willem Hendrik; Verhaagen, J

    1999-01-01

    The adult mammalian olfactory neuroepithelium is an unusual neural tissue, since it maintains its capacity to form new neurons throughout life. Newly formed neurons differentiate in the basal layers of the olfactory neuroepithelium and express B-50/GAP-43, a protein implicated in neurite outgrowth.

  15. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W

    1997-01-01

    Adhalin, or alpha-sarcoglycan, is a 50-kDa glycoprotein that was originally characterized as a muscle membrane protein. The importance of adhalin is suggested by the diseases associated with its absence, notably the limb-girdle muscular dystrophies. However, the function of adhalin is unknown...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...... in vitro. The proper localization of adhalin to the muscle cell membrane was observed only in late stages of myotube maturation, coincident with the re-distribution of caveolin-3 and dystrophin. These data suggest that adhalin is highly specific for striated muscle and that it is linked with the formation...

  16. Gross morphology and histology of the olfactory organ of the Greenland shark Somniosus microcephalus

    DEFF Research Database (Denmark)

    Ferrando, S.; Gallus, L.; Ghigliotti, L.

    2016-01-01

    The Greenland shark (Somniosus microcephalus) is the largest predatory fish in Arctic waters. Knowledge of the fundamental biology and ecological role of the Greenland shark is limited, and the sensory biology of the Greenland shark has been poorly studied. Given the potential relevant contribution...... of chemoreception to the sensory capability of the Greenland shark to forage and navigate in low-light environments, we examined the architecture of the peripheral olfactory organ (the olfactory rosette) through morphological, histological and immunohistochemical assays. We found that each olfactory rosette...... neurons, presence of unusually large cells along the olfactory fiber bundles) deserve further investigation. Overall, the structure of the olfactory rosette suggests a well-developed olfactory capability for the Greenland shark coherent with a bentho-pelagic lifestyle....

  17. Selective gene expression by postnatal electroporation during olfactory interneuron neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexander T Chesler

    Full Text Available Neurogenesis persists in the olfactory system throughout life. The mechanisms of how new neurons are generated, how they integrate into circuits, and their role in coding remain mysteries. Here we report a technique that will greatly facilitate research into these questions. We found that electroporation can be used to robustly and selectively label progenitors in the Subventicular Zone. The approach was performed postnatally, without surgery, and with near 100% success rates. Labeling was found in all classes of interneurons in the olfactory bulb, persisted to adulthood and had no adverse effects. The broad utility of electroporation was demonstrated by encoding a calcium sensor and markers of intracellular organelles. The approach was found to be effective in wildtype and transgenic mice as well as rats. Given its versatility, robustness, and both time and cost effectiveness, this method offers a powerful new way to use genetic manipulation to understand adult neurogenesis.

  18. Automated analyses of innate olfactory behaviors in rodents.

    Directory of Open Access Journals (Sweden)

    Qiang Qiu

    Full Text Available Olfaction based behavioral experiments are important for the investigation of sensory coding, perception, decision making and memory formation. The predominant experimental paradigms employ forced choice operant assays, which require associative learning and reinforced training. Animal performance in these assays not only reflects odor perception but also the confidence in decision making and memory. In this study, we describe a versatile and automated setup, "Poking-Registered Olfactory Behavior Evaluation System" (PROBES, which can be adapted to perform multiple olfactory assays. In addition to forced choice assays, we employ this system to examine animal's innate ability for odor detection, discrimination and preference without elaborate training procedures. These assays provide quantitative measurements of odor discrimination and robust readouts of odor preference. Using PROBES, we find odor detection thresholds are at lower concentrations in naïve animals than those determined by forced choice assays. PROBES-based automated assays provide an efficient way of analyzing innate odor-triggered behaviors.

  19. Organization of the olfactory system of nymphalidae butterflies.

    Science.gov (United States)

    Carlsson, Mikael A; Schäpers, Alexander; Nässel, Dick R; Janz, Niklas

    2013-05-01

    Olfaction is in many species the most important sense, essential for food search, mate finding, and predator avoidance. Butterflies have been considered a microsmatic group of insects that mainly rely on vision due to their diurnal lifestyle. However, an emerging number of studies indicate that butterflies indeed use the sense of smell for locating food and oviposition sites. To unravel the neural substrates for olfaction, we performed an anatomical study of 2 related butterfly species that differ in food and host plant preference. We found many of the anatomical structures and pathways, as well as distribution of neuroactive substances, to resemble that of their nocturnal relatives among the Lepidoptera. The 2 species differed in the number of one type of olfactory sensilla, thus indicating a difference in sensitivity to certain compounds. Otherwise no differences could be observed. Our findings suggest that the olfactory system in Lepidoptera is well conserved despite the long evolutionary time since butterflies and moths diverged from a common ancestor.

  20. Insect olfactory coding and memory at multiple timescales.

    Science.gov (United States)

    Gupta, Nitin; Stopfer, Mark

    2011-10-01

    Insects can learn, allowing them great flexibility for locating seasonal food sources and avoiding wily predators. Because insects are relatively simple and accessible to manipulation, they provide good experimental preparations for exploring mechanisms underlying sensory coding and memory. Here we review how the intertwining of memory with computation enables the coding, decoding, and storage of sensory experience at various stages of the insect olfactory system. Individual parts of this system are capable of multiplexing memories at different timescales, and conversely, memory on a given timescale can be distributed across different parts of the circuit. Our sampling of the olfactory system emphasizes the diversity of memories, and the importance of understanding these memories in the context of computations performed by different parts of a sensory system. Published by Elsevier Ltd.

  1. Polymers with embedded chemical indicators as an artificial olfactory mucosa.

    Science.gov (United States)

    Dini, Francesca; Filippini, Daniel; Paolesse, Roberto; D'Amico, Arnaldo; Lundström, Ingemar; Di Natale, Corrado

    2010-06-01

    Physiological investigations suggest that the olfactory mucosa probably plays an ancillary role in the recognition of odours introducing a sort of chromatographic separation that, together with the zonal distribution of olfactory receptors, gives place to selective spatio-temporal response patterns. It has been recently suggested that this behaviour may be simulated by chemical sensors embedded in continuous polymer layers. In this paper, in analogy to the biology of olfaction, a simple and compact platform able to separate and detect gases and vapours on the basis of their diffusion properties is proposed. In such a system, broadly selective colour indicators, such as metalloporphyrins, are embedded in continuous layers of polymers with different sorption properties. The exposure to various alcohols and amines shows that the porphyrins are mainly responsible for the recognition of the molecular family, while the occurring spatio-temporal signal patterns make possible the identification of the individual chemical species.

  2. Composition of the Migratory Mass During Development of the Olfactory Nerve

    OpenAIRE

    Miller, Alexandra M.; Treloar, Helen B.; Greer, Charles A.

    2010-01-01

    The embryonic development of the olfactory nerve includes the differentiation of cells within the olfactory placode, migration of cells into the mesenchyme from the placode, and extension of axons by the olfactory sensory neurons (OSNs). The coalition of both placode-derived migratory cells and OSN axons within the mesenchyme is collectively termed the “migratory mass.” Here we address the sequence and coordination of the events that give rise to the migratory mass. Using neuronal and develop...

  3. On the nose: Olfactory disturbances in patients with transient epileptic amnesia.

    Science.gov (United States)

    Savage, Sharon A; Butler, Christopher R; Milton, Fraser; Han, Yang; Zeman, Adam Z

    2017-01-01

    While olfactory hallucinations are relatively rare in epilepsy, a high prevalence (up to 42%) has been reported in one form - Transient Epileptic Amnesia (TEA). TEA is characterized by recurring amnestic seizures and is commonly associated with persistent interictal memory deficits. Despite reports of changes in smell, olfactory ability has not been objectively assessed in this group. The aim of this study was to measure olfactory ability in patients with TEA and explore whether olfactory symptoms relate to other clinical variables. Fifty-five participants with TEA were recruited from The Impairment of Memory in Epilepsy project database. The presence of olfactory symptoms was obtained via case notes and clinical interview. Participants completed questionnaires to evaluate their olfaction and memory function subjectively. Olfactory ability was measured using the University of Pennsylvania Smell Identification Test (UPSIT). TEA participants' performance was compared to 50 matched healthy control participants. A subset of TEA participants (n=26) also completed a battery of memory tests including standard neuropsychological measures, and assessment of accelerated long-term forgetting and autobiographical memory. Olfactory hallucinations were reported in 55% of patients with TEA. A significant reduction in smell identification (UPSIT) was found between patients with TEA and healthy controls (p<0.001). Epilepsy variables, including history of olfactory hallucinations, were not predictive of olfactory ability. Patients reported ongoing memory difficulties and performed below normative values on objective tests. While no correlation was found between objective measures of memory and olfactory performance, subjective complaints of route finding difficulty was associated with UPSIT score. Impairments in odor identification are common in patients with TEA and exceed changes that occur in normal aging. Olfactory hallucinations occurs in approximately half of patients with TEA

  4. [The ENT specialist's responsibility in the diagnosis of the olfactory meningeoma (author's transl)].

    Science.gov (United States)

    Schmitt, H E; Ahyai, A; Spoerri, O

    1982-02-01

    The principal symptoms associate with olfactory groove meningeomas are anosmia and headache which lead the patient to an ENT specialist. Frontal sinusitis, migraine and neuralgia are the most frequent incorrect diagnosis. Positive radiological changes are found frequently on the plain films of patients with these olfactory tumors, even up to 70% according to the literature. It is important to bear this in mind regarding olfactory groove meningeomas to avoid mistakes in diagnosis.

  5. Nitric Oxide-Mediated Modulation of Central Network Dynamics during Olfactory Perception.

    Directory of Open Access Journals (Sweden)

    Satoshi Watanabe

    Full Text Available Nitric oxide (NO modulates the dynamics of central olfactory networks and has been implicated in olfactory processing including learning. Land mollusks have a specialized olfactory lobe in the brain called the procerebral (PC lobe. The PC lobe produces ongoing local field potential (LFP oscillation, which is modulated by olfactory stimulation. We hypothesized that NO should be released in the PC lobe in response to olfactory stimulation, and to prove this, we applied an NO electrode to the PC lobe of the land slug Limax in an isolated tentacle-brain preparation. Olfactory stimulation applied to the olfactory epithelium transiently increased the NO concentration in the PC lobe, and this was blocked by the NO synthase inhibitor L-NAME at 3.7 mM. L-NAME at this concentration did not block the ongoing LFP oscillation, but did block the frequency increase during olfactory stimulation. Olfactory stimulation also enhanced spatial synchronicity of activity, and this response was also blocked by L-NAME. Single electrical stimulation of the superior tentacle nerve (STN mimicked the effects of olfactory stimulation on LFP frequency and synchronicity, and both of these effects were blocked by L-NAME. L-NAME did not block synaptic transmission from the STN to the nonbursting (NB-type PC lobe neurons, which presumably produce NO in an activity-dependent manner. Previous behavioral experiments have revealed impairment of olfactory discrimination after L-NAME injection. The recording conditions in the present work likely reproduce the in vivo brain state in those behavioral experiments. We speculate that the dynamical effects of NO released during olfactory perception underlie precise odor representation and memory formation in the brain, presumably through regulation of NB neuron activity.

  6. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. [Interests of an olfactory stimulation activity in a nursing home].

    Science.gov (United States)

    Garnaud, Mahlia; Rexand, Franck

    2016-01-01

    The comparison between the memories productions of residents in a nursing home through two reminiscence activities, one including olfaction and not the other one, can highlight an increasing occurrence of recent memories in the case of olfactory activity. A longer talk time is also observed and a better self-esteem can be assessed. This suggests the possibility of a specific relational and psychotherapeutic work. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Automated Analyses of Innate Olfactory Behaviors in Rodents

    OpenAIRE

    Qiu, Qiang; Scott, Aaron; Scheerer, Hayley; Sapkota, Nirjal; Lee, Daniel K.; Ma, Limei; Yu, C. Ron

    2014-01-01

    Olfaction based behavioral experiments are important for the investigation of sensory coding, perception, decision making and memory formation. The predominant experimental paradigms employ forced choice operant assays, which require associative learning and reinforced training. Animal performance in these assays not only reflects odor perception but also the confidence in decision making and memory. In this study, we describe a versatile and automated setup, "Poking-Registered Olfactory Beha...

  9. Hunger state affects both olfactory abilities and gustatory sensitivity.

    Science.gov (United States)

    Hanci, Deniz; Altun, Huseyin

    2016-07-01

    Chemical senses such as odor, taste and appearance are directly related with appetite. Understanding the relation between appetite and flavor is getting more important due to increasing number of obese patients worldwide. The literature on the studies investigating the change in olfactory abilities and gustatory sensitivity mostly performed using food-related odors and tastes rather than standardized tests were developed to study olfaction and gustation. Therefore, results are inconsistent and the relationship between olfactory and gustatory sensitivity with respect to the actual state of human satiety is still not completely understood. Here, for the first time in literature, we investigated the change in both olfactory abilities and gustatory sensitivity in hunger and in satiety using 123 subjects (37 men, 86 women; mean age 31.4 years, age range 21-41 years). The standardized Sniffin' Sticks Extended Test and Taste Strips were used for olfactory testing and gustatory sensitivity, respectively. TDI score (range 1-48) was calculated as the collective scores of odor threshold (T), odor discrimination (D) and odor identification (I). The evaluation was performed in two successive days where the hunger state of test subjects was confirmed by blood glucose test strips (mean blood glucose level 90.0 ± 5.6 mg/dl in hunger and 131.4 ± 8.1 mg/dl in satiety). The results indicated statistically significant decrease in olfaction in satiety compared to hunger (mean TDI 39.3 ± 1.1 in hunger, 37.4 ± 1.1 in satiety, p hunger (p hunger state.

  10. Osmophobia and olfactory functions in patients with migraine.

    Science.gov (United States)

    Kayabaşoglu, Gürkan; Altundag, Aytug; Kotan, Dilcan; Dizdar, Denizhan; Kaymaz, Recep

    2017-02-01

    Olfactory dysfunction and migraine has been associated for a long time. In this study, we planned to compare olfactory functions in patients with migraine and osmophobia with patients having migraine but no osmophobia, in addition with a normal control group using "Sniffin' Sticks" test. The main distinction of this study is that all qualitative and quantitative properties of olfactory functions; threshold, discrimination and identification, are evaluated separately and jointly. Thirty healthy person aged between 16 and 56 (18 women, 12 men) and 60 migraine patients aged between 15 and 54 (39 women, 21 man) were included in the study. All patients have been inquired about osmophobia and have been assessed with Hedonic tone assessment. Osmophobia has been tested for perfume, cigarette smoke, leather, stale food, soy sauce, fish, spices and coffee smells. Olfactory functions has been assessed with "Sniffin' Sticks" smell test. Thresholds, discrimination and identification have been determined for each patient. In migraine patients with osmophobia, threshold was 7.75 ± 2.3, in migraine patients without osmophobia threshold was 8.25 ± 1.5 and threshold was 10.75 ± 1.3 for the control group. Discrimination score was 6 ± 1.2 in migraine patients with osmophobia, 9 ± 0.8 in patients without osmophobia and was 12 ± 1.4 in the control group. In migraine patient with or without osmophobia Threshold/Discrimination/Identification (TDI) scores were lower than the control group. The most important parameter in our study is that discrimination scores were especially lower in patients with osmophobia. We believe that this decrease in discrimination in migraine patients with osmophobia; who claim that they smell everything and they are sensitive to all smells, is significant. Further studies about smell discrimination will help better understand some conditions; especially anosmia and hyposmia after upper respiratory tract infections and parosmia.

  11. Facial, Olfactory, and Vocal Cues to Female Reproductive Value

    OpenAIRE

    Susanne Röder; Bernhard Fink; Jones, Benedict C.

    2013-01-01

    Facial, olfactory, and vocal cues may advertise women's fertility. However, most of the evidence for this proposal has come from studies of changes in young adult women's attractiveness over the menstrual cycle. By contrast with this emphasis on changes in attractiveness over the menstrual cycle, possible changes in women's attractiveness over their lifespan have received little attention. The present study investigated men's ratings of young girls' (11–15 years old), adult women's (19–30 yea...

  12. Adult neurogenesis supports short-term olfactory memory.

    Science.gov (United States)

    Arenkiel, Benjamin R

    2010-06-01

    Adult neurogenesis has captivated neuroscientists for decades, with hopes that understanding the programs underlying this phenomenon may provide unique insight toward avenues for brain repair. Interestingly, however, despite intense molecular and cellular investigation, the evolutionary roles and biological functions for ongoing neurogenesis have remained elusive. Here I review recent work published in the Journal of Neuroscience that reveals a functional role for continued neurogenesis toward forming short-term olfactory memories.

  13. Evidence for olfactory search in wandering albatross, Diomedea exulans

    OpenAIRE

    Nevitt, Gabrielle A.; Losekoot, Marcel; Weimerskirch, Henri

    2008-01-01

    Wandering albatrosses (Diomedea exulans) forage over thousands of square kilometers of open ocean for patchily distributed live prey and carrion. These birds have large olfactory bulbs and respond to fishy-scented odors in at-sea trials, suggesting that olfaction plays a role in natural foraging behavior. With the advent of new, fine-scale tracking technologies, we are beginning to explore how birds track prey in the pelagic environment, and we relate these observations to models of odor tran...

  14. Auditory-olfactory synesthesia coexisting with auditory-visual synesthesia.

    Science.gov (United States)

    Jackson, Thomas E; Sandramouli, Soupramanien

    2012-09-01

    Synesthesia is an unusual condition in which stimulation of one sensory modality causes an experience in another sensory modality or when a sensation in one sensory modality causes another sensation within the same modality. We describe a previously unreported association of auditory-olfactory synesthesia coexisting with auditory-visual synesthesia. Given that many types of synesthesias involve vision, it is important that the clinician provide these patients with the necessary information and support that is available.

  15. A coupled-oscillator model of olfactory bulb gamma oscillations.

    Directory of Open Access Journals (Sweden)

    Guoshi Li

    2017-11-01

    Full Text Available The olfactory bulb transforms not only the information content of the primary sensory representation, but also its underlying coding metric. High-variance, slow-timescale primary odor representations are transformed by bulbar circuitry into secondary representations based on principal neuron spike patterns that are tightly regulated in time. This emergent fast timescale for signaling is reflected in gamma-band local field potentials, presumably serving to efficiently integrate olfactory sensory information into the temporally regulated information networks of the central nervous system. To understand this transformation and its integration with interareal coordination mechanisms requires that we understand its fundamental dynamical principles. Using a biophysically explicit, multiscale model of olfactory bulb circuitry, we here demonstrate that an inhibition-coupled intrinsic oscillator framework, pyramidal resonance interneuron network gamma (PRING, best captures the diversity of physiological properties exhibited by the olfactory bulb. Most importantly, these properties include global zero-phase synchronization in the gamma band, the phase-restriction of informative spikes in principal neurons with respect to this common clock, and the robustness of this synchronous oscillatory regime to multiple challenging conditions observed in the biological system. These conditions include substantial heterogeneities in afferent activation levels and excitatory synaptic weights, high levels of uncorrelated background activity among principal neurons, and spike frequencies in both principal neurons and interneurons that are irregular in time and much lower than the gamma frequency. This coupled cellular oscillator architecture permits stable and replicable ensemble responses to diverse sensory stimuli under various external conditions as well as to changes in network parameters arising from learning-dependent synaptic plasticity.

  16. The h-current in periglomerular dopaminergic neurons of the mouse olfactory bulb.

    Science.gov (United States)

    Pignatelli, Angela; Borin, Mirta; Fogli Iseppe, Alex; Gambardella, Cristina; Belluzzi, Ottorino

    2013-01-01

    The properties of the hyperpolarization-activated cation current (I(h)) were investigated in rat periglomerular dopaminergic neurons using patch-clamp recordings in thin slices. A reliable identification of single dopaminergic neurons was made possible by use of a transgenic line of mice expressing eGFP under the tyrosine hydroxylase promoter. At 37 °C and minimizing the disturbance of the intracellular milieu with perforated patches, this current shows a midpoint of activation around -82.7 mV, with a significant level of opening already at rest, thereby giving a substantial contribution to the resting potential, and ultimately playing a relevant function in the control of the cell excitability. The blockage of I(h) has a profound influence on the spontaneous firing of these neurons, which result as strongly depressed. However the effect is not due to a direct role of the current in the pacemaker process, but to the I(h) influence on the resting membrane potential. I(h) kinetics is sensitive to the intracellular levels of cAMP, whose increase promotes a shift of the activation curve towards more positive potentials. The direct application of DA and 5-HT neurotransmitters, physiologically released onto bulbar dopaminergic neurons and known to act on metabotropic receptors coupled to the cAMP pathway, do not modifythe I(h) amplitude. On the contrary, noradrenaline almost halves the I(h) amplitude. Our data indicate that the HCN channels do not participate directly to the pacemaker activity of periglomerular dopaminergic neurons, but influence their resting membrane potential by controlling the excitability profile of these cells, and possibly affecting the processing of sensory information taking place at the entry of the bulbar circuitry.

  17. The h-current in periglomerular dopaminergic neurons of the mouse olfactory bulb.

    Directory of Open Access Journals (Sweden)

    Angela Pignatelli

    Full Text Available The properties of the hyperpolarization-activated cation current (I(h were investigated in rat periglomerular dopaminergic neurons using patch-clamp recordings in thin slices. A reliable identification of single dopaminergic neurons was made possible by use of a transgenic line of mice expressing eGFP under the tyrosine hydroxylase promoter. At 37 °C and minimizing the disturbance of the intracellular milieu with perforated patches, this current shows a midpoint of activation around -82.7 mV, with a significant level of opening already at rest, thereby giving a substantial contribution to the resting potential, and ultimately playing a relevant function in the control of the cell excitability. The blockage of I(h has a profound influence on the spontaneous firing of these neurons, which result as strongly depressed. However the effect is not due to a direct role of the current in the pacemaker process, but to the I(h influence on the resting membrane potential. I(h kinetics is sensitive to the intracellular levels of cAMP, whose increase promotes a shift of the activation curve towards more positive potentials. The direct application of DA and 5-HT neurotransmitters, physiologically released onto bulbar dopaminergic neurons and known to act on metabotropic receptors coupled to the cAMP pathway, do not modifythe I(h amplitude. On the contrary, noradrenaline almost halves the I(h amplitude. Our data indicate that the HCN channels do not participate directly to the pacemaker activity of periglomerular dopaminergic neurons, but influence their resting membrane potential by controlling the excitability profile of these cells, and possibly affecting the processing of sensory information taking place at the entry of the bulbar circuitry.

  18. Titration of biologically active amyloid-β seeds in a transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Morales, Rodrigo; Bravo-Alegria, Javiera; Duran-Aniotz, Claudia; Soto, Claudio

    2015-03-23

    Experimental evidence in animal models suggests that misfolded Amyloid-β (Aβ) spreads in disease following a prion-like mechanism. Several properties characteristics of infectious prions have been shown for the induction of Aβ aggregates. However, a detailed titration of Aβ misfolding transmissibility and estimation of the minimum concentration of biologically active Aβ seeds able to accelerate pathological changes has not yet been performed. In this study, brain extracts from old tg2576 animals were serially diluted and intra-cerebrally injected into young subjects from the same transgenic line. Animals were sacrificed several months after treatment and brain slices were analyzed for amyloid pathology. We observed that administration of misfolded Aβ was able to significantly accelerate amyloid deposition in young mice, even when the original sample was diluted a million times. The titration curve obtained in this experiment was compared to the natural Aβ load spontaneously accumulated by these mice overtime. Our findings suggest that administration of the largest dose of Aβ seeds led to an acceleration of pathology equivalent to over a year. These results show that active Aβ seeds present in the brain can seed amyloidosis in a titratable manner, similarly as observed for infectious prions.

  19. Biophysical constraints on lateral inhibition in the olfactory bulb.

    Science.gov (United States)

    McIntyre, Alexa B R; Cleland, Thomas A

    2016-06-01

    The mitral cells (MCs) of the mammalian olfactory bulb (OB) constitute one of two populations of principal neurons (along with middle/deep tufted cells) that integrate afferent olfactory information with top-down inputs and intrinsic learning and deliver output to downstream olfactory areas. MC activity is regulated in part by inhibition from granule cells, which form reciprocal synapses with MCs along the extents of their lateral dendrites. However, with MC lateral dendrites reaching over 1.5 mm in length in rats, the roles of distal inhibitory synapses pose a quandary. Here, we systematically vary the properties of a MC model to assess the capacity of inhibitory synaptic inputs on lateral dendrites to influence afferent information flow through MCs. Simulations using passivized models with varying dendritic morphologies and synaptic properties demonstrated that, even with unrealistically favorable parameters, passive propagation fails to convey effective inhibitory signals to the soma from distal sources. Additional simulations using an active model exhibiting action potentials, subthreshold oscillations, and a dendritic morphology closely matched to experimental values further confirmed that distal synaptic inputs along the lateral dendrite could not exert physiologically relevant effects on MC spike timing at the soma. Larger synaptic conductances representative of multiple simultaneous inputs were not sufficient to compensate for the decline in signal with distance. Reciprocal synapses on distal MC lateral dendrites may instead serve to maintain a common fast oscillatory clock across the OB by delaying spike propagation within the lateral dendrites themselves. Copyright © 2016 the American Physiological Society.

  20. The olfactory bulb volume in patients with idiopathic Parkinson's disease.

    Science.gov (United States)

    Paschen, L; Schmidt, N; Wolff, S; Cnyrim, C; van Eimeren, T; Zeuner, K E; Deuschl, G; Witt, K

    2015-07-01

    This study addresses the question of whether the neuropathological findings on the olfactory bulb (OB) in idiopathic Parkinson's disease (IPD) correspond to a detectable change in volume of the OB. Additionally, the relationship between OB volume and residual olfactory function, clinical disease characteristics and age are investigated. Fifty-two IPD patients were investigated and compared to 31 healthy age-matched controls. All participants were scanned using a 3 T magnetic resonance imaging MRI scanner including a T2 DRIVE sequence in coronal slices through the OB. The OB volumes were measured via manual segmentation of the OB. Olfactory testing was carried out using the Sniffin' Sticks test battery. The OB volume in the IPD group was 42.1 mm³ (SD ± 11.6) for the right and 41.5 mm³ (SD ± 11.7) for the left OB and showed no difference from the controls. Additionally, there were no significant correlations between OB volume and disease characteristics such as disease duration or Unified Parkinson's Disease Rating Scale motor score. Likewise, patients' residual smell function did not correlate with their OB volume. In contrast, controls indicated a correlation between smell function and OB volume. The study shows that high resolution MRI does not show a detectable volume loss of the OB in PD patients. It is concluded that OB measurement using in vivo high resolution MRI at 3 T is not helpful to identify IPD. © 2015 EAN.

  1. Olfactory bulb volume predicts therapeutic outcome in major depression disorder.

    Science.gov (United States)

    Negoias, Simona; Hummel, Thomas; Symmank, Anja; Schellong, Julia; Joraschky, Peter; Croy, Ilona

    2016-06-01

    The volume of the olfactory bulb (OB) is strongly reduced in patients with major depressive disorder (MDD) and this group exhibits markedly decreased olfactory function. It has been suggested that olfactory input is important for maintaining balance in limbic neurocircuits. The aim of our study was to investigate whether reduced OB volume is associated with response to therapy in MDD. Twenty-four inpatients (all women, age 21-49 years, mean 38 ± 10 years SD) with MDD and 36 healthy controls (all women, age 20-52 years, mean 36 ± 10 years SD) underwent structural MRI. OB volume was compared between responders (N = 13) and non-responders (N = 11) to psychotherapy. Retest of OB volume was performed about 6 months after the end of therapy in nine of the patients. Therapy responders exhibited no significant difference in OB volume compared to healthy controls. However, average OB volume of non-responders was 23 % smaller compared to responders (p = .0011). Furthermore, OB volume was correlated with the change of depression severity (r = .46, p = .024). Volume of the OB did not change in the course of therapy. OB volume may be a biological vulnerability factor for the occurrence and/or maintenance of depression, at least in women.

  2. Coactivation of Gustatory and Olfactory Signals in Flavor Perception

    Science.gov (United States)

    Veldhuizen, Maria G.; Shepard, Timothy G.; Wang, Miao-Fen

    2010-01-01

    It is easier to detect mixtures of gustatory and olfactory flavorants than to detect either component alone. But does the detection of mixtures exceed the level predicted by probability summation, assuming independent detection of each component? To answer this question, we measured simple response times (RTs) to detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral [olfactory], sucrose–citral mixture) or water, presented into the mouth by a computer-operated, automated flow system. Subjects were instructed to press a button as soon as they detected any of the 3 nonwater stimuli. Responses to the mixtures were faster (RTs smaller) than predicted by a model of probability summation of independently detected signals, suggesting positive coactivation (integration) of gustation and retronasal olfaction in flavor perception. Evidence for integration appeared mainly in the fastest 60% of the responses, indicating that integration arises relatively early in flavor processing. Results were similar when the 3 possible flavorants, and water, were interleaved within the same session (experimental condition), and when each flavorant was interleaved with water only (control conditions). This outcome suggests that subjects did not attend selectively to one flavor component or the other in the experimental condition and further supports the conclusion that (late) decisional or attentional strategies do not exert a large influence on the gustatory–olfactory flavor integration. PMID:20032112

  3. Olfactory dysfunction in incidental Lewy body disease and Parkinson's disease.

    Science.gov (United States)

    Driver-Dunckley, Erika; Adler, Charles H; Hentz, Joseph G; Dugger, Brittany N; Shill, Holly A; Caviness, John N; Sabbagh, Marwan N; Beach, Thomas G

    2014-11-01

    Olfactory dysfunction in Parkinson's disease (PD) is well-established and may represent one of the earliest signs of the disease. The objective of this study was to evaluate the relationship of olfactory dysfunction, using the University of Pennsylvania Smell Identification Test (UPSIT), to clinical and pathological parameters of clinicopathologically diagnosed PD (n = 10), incidental Lewy body disease (ILBD) (n = 13), and identically assessed controls who lacked a neurodegenerative disease (n = 69). Mean UPSIT scores were significantly lower in PD (16.3, p < 0.001) and ILBD (22.2, p = 0.004) compared to controls (27.7). Using an UPSIT cutoff score of <22 (the 15th percentile) the sensitivity for detecting PD was 9/10 (90%) and ILBD 6/13 (46%), while the specificity was 86% (Controls with score of <22 = 10/69). These results add to the growing body of evidence suggesting that olfactory testing could be useful as a screening tool for identifying early, pre-motor PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Olfactory processing in adults with autism spectrum disorders.

    Science.gov (United States)

    Wicker, Bruno; Monfardini, Elisabetta; Royet, Jean-Pierre

    2016-01-01

    As evidenced in the DSM-V, autism spectrum disorders (ASD) are often characterized by atypical sensory behavior (hyper- or hypo-reactivity), but very few studies have evaluated olfactory abilities in individuals with ASD. Fifteen adults with ASD and 15 typically developing participants underwent olfactory tests focused on superficial (suprathreshold detection task), perceptual (intensity and pleasantness judgment tasks), and semantic (identification task) odor processing. In terms of suprathreshold detection performance, decreased discrimination scores and increased bias scores were observed in the ASD group. Furthermore, the participants with ASD exhibited increased intensity judgment scores and impaired scores for pleasantness judgments of unpleasant odorants. Decreased identification performance was also observed in the participants with ASD compared with the typically developing participants. This decrease was partly attributed to a higher number of near misses (a category close to veridical labels) among the participants with ASD than was observed among the typically developing participants. The changes in discrimination and bias scores were the result of a high number of false alarms among the participants with ASD, which suggests the adoption of a liberal attitude in their responses. Atypical intensity and pleasantness ratings were associated with hyperresponsiveness and flattened emotional reactions, respectively, which are typical of participants with ASD. The high number of near misses as non-veridical labels suggested that categorical processing is functional in individuals with ASD and could be explained by attention-deficit/hyperactivity disorder. These findings are discussed in terms of dysfunction of the olfactory system.

  5. Evidence for partial overlap of male olfactory cues in lampreys

    Science.gov (United States)

    Buchinger, Tyler J.; Li, Ke; Huertas, Mar; Baker, Cindy F.; Jia, Liang; Hayes, Michael C.; Li, Weiming; Johnson, Nicholas S.

    2016-01-01

    Animals rely on a mosaic of complex information to find and evaluate mates. Pheromones, often comprised of multiple components, are considered to be particularly important for species-recognition in many species. While the evolution of species-specific pheromone blends is well-described in many insects, very few vertebrate pheromones have been studied in a macro-evolutionary context. Here, we report a phylogenetic comparison of multi-component male odours that guide reproduction in lampreys. Chemical profiling of sexually mature males from eleven species of lamprey, representing six of ten genera and two of three families, indicated the chemical profiles of sexually mature male odours are partially shared among species. Behavioural assays conducted with four species sympatric in the Laurentian Great Lakes indicated asymmetric female responses to heterospecific odours, where Petromyzon marinus were attracted to male odour collected from all species tested but other species generally preferred only the odour of conspecifics. Electro-olfactogram recordings from P. marinusindicated that although P. marinus exhibited behavioural responses to odours from males of all species, at least some of the compounds that elicited olfactory responses were different in conspecific male odours compared to heterospecific male odours. We conclude that some of the compounds released by sexually mature males are shared among species and elicit olfactory and behavioural responses in P. marinus, and suggest that our results provide evidence for partial overlap of male olfactory cues among lampreys. Further characterization of the chemical identities of odour components is needed to confirm shared pheromones among species.

  6. Detecting gustatory-olfactory flavor mixtures: models of probability summation.

    Science.gov (United States)

    Marks, Lawrence E; Veldhuizen, Maria G; Shepard, Timothy G; Shavit, Adam Y

    2012-03-01

    Odorants and flavorants typically contain many components. It is generally easier to detect multicomponent stimuli than to detect a single component, through either neural integration or probability summation (PS) (or both). PS assumes that the sensory effects of 2 (or more) stimulus components (e.g., gustatory and olfactory components of a flavorant) are detected in statistically independent channels, that each channel makes a separate decision whether a component is detected, and that the behavioral response depends solely on the separate decisions. Models of PS traditionally assume high thresholds for detecting each component, noise being irrelevant. The core assumptions may be adapted, however, to signal-detection theory, where noise limits detection. The present article derives predictions of high-threshold and signal-detection models of independent-decision PS in detecting gustatory-olfactory flavorants, comparing predictions in yes/no and 2-alternative forced-choice tasks using blocked and intermixed stimulus designs. The models also extend to measures of response times to suprathreshold flavorants. Predictions derived from high-threshold and signal-detection models differ markedly. Available empirical evidence on gustatory-olfactory flavor detection suggests that neither the high-threshold nor the signal-detection versions of PS can readily account for the results, which likely reflect neural integration in the flavor system.

  7. Coactivation of gustatory and olfactory signals in flavor perception.

    Science.gov (United States)

    Veldhuizen, Maria G; Shepard, Timothy G; Wang, Miao-Fen; Marks, Lawrence E

    2010-02-01

    It is easier to detect mixtures of gustatory and olfactory flavorants than to detect either component alone. But does the detection of mixtures exceed the level predicted by probability summation, assuming independent detection of each component? To answer this question, we measured simple response times (RTs) to detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral [olfactory], sucrose-citral mixture) or water, presented into the mouth by a computer-operated, automated flow system. Subjects were instructed to press a button as soon as they detected any of the 3 nonwater stimuli. Responses to the mixtures were faster (RTs smaller) than predicted by a model of probability summation of independently detected signals, suggesting positive coactivation (integration) of gustation and retronasal olfaction in flavor perception. Evidence for integration appeared mainly in the fastest 60% of the responses, indicating that integration arises relatively early in flavor processing. Results were similar when the 3 possible flavorants, and water, were interleaved within the same session (experimental condition), and when each flavorant was interleaved with water only (control conditions). This outcome suggests that subjects did not attend selectively to one flavor component or the other in the experimental condition and further supports the conclusion that (late) decisional or attentional strategies do not exert a large influence on the gustatory-olfactory flavor integration.

  8. The effect of desflurane on postoperative olfactory memory.

    Science.gov (United States)

    Yildiz, I; Bayır, H; Saglam, I; Sereflican, M; Bilgi, M; Yurttas, V; Demirhan, A; Tekelioglu, U Y; Kocoglu, H

    2016-05-01

    In this study, we investigated the effects of desflurane 6%, on olfactory memory. This is a prospective clinical study performed with 40 patients aged 18-60 who had elective surgery and American Society of Anesthesiologists (ASA) physical status I-III. The Brief Smell Identification Test (BSIT) was used for evaluating patients' olfactory memories before and after the surgery. Patients received standard general anesthesia protocol and routine monitoring. For induction, 1.5 mg/kg of fentanyl, 2 mg/kg of propofol, and 0.5 mg/kg of rocuronium bromide were administered. Anesthesia was maintained with the inhalational of anesthetic desflurane (6%). The scores are recorded 30 minutes before the surgery and when the Aldrete Recovery Score reached 10 in the postoperative period. Preoperative and postoperative results were compared and p-values 0.05). We have observed for the first time in the literature that general anesthesia using desflurane (6%) did not affect short-term olfactory memory. Further studies will be necessary to confirm our findings with larger sample size.

  9. Short-term memory in olfactory network dynamics

    Science.gov (United States)

    Stopfer, Mark; Laurent, Gilles

    1999-12-01

    Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas.. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.

  10. Effects of Caffeine on Olfactory Learning in Crickets.

    Science.gov (United States)

    Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro

    2016-10-01

    Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

  11. Nanoparticle transport across in vitro olfactory cell monolayers.

    Science.gov (United States)

    Gartziandia, Oihane; Egusquiaguirre, Susana Patricia; Bianco, John; Pedraz, José Luis; Igartua, Manoli; Hernandez, Rosa Maria; Préat, Véronique; Beloqui, Ana

    2016-02-29

    Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Olfactory discrimination in the western lowland gorilla, Gorilla gorilla gorilla.

    Science.gov (United States)

    Hepper, Peter G; Wells, Deborah L

    2012-04-01

    The olfactory abilities of great apes have been subject to little empirical investigation, save for a few observational reports. This study, using an habituation/dishabituation task, provides experimental evidence for a core olfactory ability, namely, olfactory discrimination, in the gorilla. In Experiment 1, six zoo-housed western lowland gorillas were individually presented with the same odour on four trials, and with a novel odour on the fifth trial. Odours (almond and vanilla) were presented on plastic balls, and behavioural responses of sniffing and chewing/licking the balls were recorded. A second experiment presented the same odour on four trials and no odour on the fifth to examine whether any dishabituation was due to the presence of a new odour or the absence of the familiar odour. Gorillas habituated their behaviour with repeated presentation of the same odour, but dishabituated, i.e. increased sniffing and chewing/licking, when presented with the novel odour. No dishabituation was noted when using water as the stimulus across all trials or when used as the novel odour. Overall, results show that gorillas are able to discriminate between odours.

  13. Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

    Directory of Open Access Journals (Sweden)

    Gianluca Polese

    2016-05-01

    Full Text Available The cephalopod olfactory organ was described for the first time in 1844 by von Kölliker, who was attracted to the pair of small pits of ciliated cells on each side of the head, below the eyes close to the mantle edge, in both octopuses and squids. Several functional studies have been conducted on decapods but very little is known about octopods. The morphology of the octopus olfactory system has been studied, but only to a limited extent on post-hatching specimens, and the only paper on adult octopus gives a minimal description of the olfactory organ. Here, we describe the detailed morphology of young male and female Octopus vulgaris olfactory epithelium, and using a combination of classical morphology and 3D reconstruction techniques, we propose a new classification for O. vulgaris olfactory sensory neurons. Furthermore, using specific markers such as olfactory marker protein (OMP and proliferating cell nuclear antigen (PCNA we have been able to identify and differentially localize both mature olfactory sensory neurons and olfactory sensory neurons involved in epithelium turnover. Taken together, our data suggest that the O. vulgaris olfactory organ is extremely plastic, capable of changing its shape and also proliferating its cells in older specimens.

  14. A direct anterior cingulate pathway to the primate primary olfactory cortex may control attention to olfaction

    Science.gov (United States)

    García-Cabezas, Miguel Á.; Barbas, Helen

    2016-01-01

    Behavioral and functional studies in humans suggest that attention plays a key role in activating the primary olfactory cortex through an unknown circuit mechanism. We report that a novel pathway from the anterior cingulate cortex, an area which has a key role in attention, projects directly to the primary olfactory cortex in rhesus monkeys, innervating mostly the anterior olfactory nucleus. Axons from the anterior cingulate cortex formed synapses mostly with spines of putative excitatory pyramidal neurons and with a small proportion of a neurochemical class of inhibitory neurons that are thought to have disinhibitory effect on excitatory neurons. This novel pathway from the anterior cingulate is poised to exert a powerful excitatory effect on the anterior olfactory nucleus, which is a critical hub for odorant processing via extensive bilateral connections with primary olfactory cortices and the olfactory bulb. Acting on the anterior olfactory nucleus, the anterior cingulate may activate the entire primary olfactory cortex to mediate the process of rapid attention to olfactory stimuli. PMID:23797208

  15. CD36 is involved in oleic acid detection by the murine olfactory system.

    Directory of Open Access Journals (Sweden)

    Sonja eOberland

    2015-09-01

    Full Text Available Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal’s preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca2+ imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

  16. Crustacean olfactory systems: A comparative review and a crustacean perspective on olfaction in insects.

    Science.gov (United States)

    Harzsch, S; Krieger, J

    2018-02-01

    Malacostracan crustaceans display a large diversity of sizes, morphs and life styles. However, only a few representatives of decapod taxa have served as models for analyzing crustacean olfaction, such as crayfish and spiny lobsters. Crustaceans bear multiple parallel chemosensory pathways represented by different populations of unimodal chemosensory and bimodal chemo- and mechanosensory sensilla on the mouthparts, the walking limbs and primarily on their two pairs of antennae. Here, we focus on the olfactory pathway associated with the unimodal chemosensory sensilla on the first antennal pair, the aesthetascs. We explore the diverse arrangement of these sensilla across malacostracan taxa and point out evolutionary transformations which occurred in the central olfactory pathway. We discuss the evolution of chemoreceptor proteins, comparative aspects of active chemoreception and the temporal resolution of crustacean olfactory system. Viewing the evolution of crustacean brains in light of energetic constraints can help us understand their functional morphology and suggests that in various crustacean lineages, the brains were simplified convergently because of metabolic limitations. Comparing the wiring of afferents, interneurons and output neurons within the olfactory glomeruli suggests a deep homology of insect and crustacean olfactory systems. However, both taxa followed distinct lineages during the evolutionary elaboration of their olfactory systems. A comparison with insects suggests their olfactory systems ö especially that of the vinegar fly ö to be superb examples for "economy of design". Such a comparison also inspires new thoughts about olfactory coding and the functioning of malacostracan olfactory systems in general. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Olfactory training induces changes in regional functional connectivity in patients with long-term smell loss

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    K. Kollndorfer

    2015-01-01

    The results of this study indicate that an olfactory training program can reorganize functional networks, although, initially, no differences in the spatial distribution of neural activation were observed.

  18. Congenital olfactory impairment is linked to cortical changes in prefrontal and limbic brain regions

    DEFF Research Database (Denmark)

    Karstensen, Helena Gásdal; Vestergaard, Martin; Baaré, William F C

    2018-01-01

    differently in individuals who suffer from lifelong olfactory deprivation relative to healthy normosmic individuals. To address this question, we examined if regional variations in gray matter volume were associated with smell ability in seventeen individuals with isolated congenital olfactory impairment (COI...... in left middle frontal gyrus and right superior frontal sulcus (SFS). COI subjects with severe olfactory impairment (anosmia) had reduced grey matter volume in the left mOFC and increased volume in right piriform cortex and SFS. Within the COI group olfactory ability, measured with the "Sniffin' Sticks...

  19. Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

    Science.gov (United States)

    Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

    2015-02-15

    Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (pmemory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

  20. Olfactory short-term memory encoding and maintenance - an event-related potential study.

    Science.gov (United States)

    Lenk, Steffen; Bluschke, Annet; Beste, Christian; Iannilli, Emilia; Rößner, Veit; Hummel, Thomas; Bender, Stephan

    2014-09-01

    This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Ocular and olfactory forebrain abnormalities within a neonatal alpaca (Vicugna pacos).

    Science.gov (United States)

    Hostnik, Eric T; Wickins, Sophie C; Conway, Julia A; Dark, Michael J

    2012-07-01

    A 5-day-old Huacaya alpaca cria (Vicugna pacos) was euthanized due to deteriorating health. At birth, the cria had ophthalmologic abnormalities, but had appropriate mentation. At 2 days of age, the cria gradually stopped suckling and began to circle. At 5 days old, the owner elected euthanasia due to declining clinical condition. Grossly, the right iris had a scalloped pupillary margin, and the right olfactory bulb was malformed. Histopathology revealed persistent hyperplastic primary vitreous bilaterally and iridal abnormalities, as well as aplasia of the olfactory ventricle, olfactory tract, and olfactory foramen on the right side.

  2. The role of sleep in the plasticity of the olfactory system.

    Science.gov (United States)

    Yamaguchi, Masahiro

    2017-05-01

    The central olfactory system mediates a variety of odor-guided behaviors crucial for maintenance of animal life. The olfactory neural circuit must be highly plastic to ensure that it responds appropriately to changing odor circumstances. Recent studies have revealed that the processing of odor information changes drastically during waking and sleep and that neural activity during sleep plays pivotal roles in the structural reorganization and functional plasticity of the olfactory system. While olfactory information from the external world is efficiently transferred to the olfactory cortex (OC) via the olfactory bulb (OB) during waking, this information flow is attenuated during slow-wave sleep: during slow-wave sleep, the OC neurons exhibit synchronous discharges without odor input under the entrainment of sharp waves in the local field potential recording. Top-down transfer of sharp-wave activity to the OB during slow-wave sleep promotes structural reorganization of the OB neural circuit. Further, the activity of the OC during sleep is affected by the olfactory experience during prior waking period, and perturbation of the sleep activity disrupts proper olfactory memory. Thus, as is seen also in the hippocampus and neocortex, the neural activities of the olfactory system during sleep likely play essential roles in circuit reorganization and memory consolidation. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  3. The inability to self-evaluate smell performance. How the vividness of mental images outweighs awareness of olfactory performance.

    Directory of Open Access Journals (Sweden)

    Kathrin eKollndorfer

    2015-05-01

    Full Text Available To rate one’s individual olfactory performance is difficult and in many cases differs clearly from validated objective olfactory performance measures. This study aimed to investigate the basis for this measurement drift between objective and subjective olfactory performance evaluation. In absence of an actual odor, one may imagine an olfactory stimulus to evaluate his subjective olfactory performance. Therefore, the impact of the vividness of mental images on self-evaluation of smell performance in patients with mild to severe olfactory dysfunction and healthy controls was investigated. Fifty-nine patients with peripheral olfactory dysfunction ranging from reduced olfactory function (hyposmia to complete loss of olfactory perception (anosmia and 16 healthy controls were included. Olfactory performance was assessed using the Sniffin’ Sticks battery, the vividness of olfactory mental images was evaluated using the Vividness of Olfactory Imagery Questionnaire (VOIQ.Decreased vividness of odor images was obtained for anosmic patients, and a trend of poorer odor imagery was determined in hyposmic patients. Multiple regression analyses revealed the VOIQ score as significant predictor for olfactory self-evaluation for hyposmic patients and healthy controls. In contrast, for anosmic patients, the only significant predictor for self-rating of olfactory performance was the TDI score. The results of this study indicate that sensory perception and mental images are closely related to each other. Furthermore, subjects who were able to perceive odors, even to a smaller extent, rely on the vividness of their mental odor images to evaluate their olfactory performance. In contrast, anosmic patients rather trust in their knowledge that they are not able to perceive odors. We are therefore able to subjectively rate our olfactory performance levels, if we are not able to perceive odors, but not if we are able to perceive olfactory input.

  4. GABAB Receptors Tune Cortical Feedback to the Olfactory Bulb.

    Science.gov (United States)

    Mazo, Camille; Lepousez, Gabriel; Nissant, Antoine; Valley, Matthew T; Lledo, Pierre-Marie

    2016-08-10

    Sensory perception emerges from the confluence of sensory inputs that encode the composition of external environment and top-down feedback that conveys information from higher brain centers. In olfaction, sensory input activity is initially processed in the olfactory bulb (OB), serving as the first central relay before being transferred to the olfactory cortex. In addition, the OB receives dense connectivity from feedback projections, so the OB has the capacity to implement a wide array of sensory neuronal computation. However, little is known about the impact and the regulation of this cortical feedback. Here, we describe a novel mechanism to gate glutamatergic feedback selectively from the anterior olfactory cortex (AOC) to the OB. Combining in vitro and in vivo electrophysiological recordings, optogenetics, and fiber-photometry-based calcium imaging applied to wild-type and conditional transgenic mice, we explore the functional consequences of circuit-specific GABA type-B receptor (GABABR) manipulation. We found that activation of presynaptic GABABRs specifically depresses synaptic transmission from the AOC to OB inhibitory interneurons, but spares direct excitation to principal neurons. As a consequence, feedforward inhibition of spontaneous and odor-evoked activity of principal neurons is diminished. We also show that tunable cortico-bulbar feedback is critical for generating beta, but not gamma, OB oscillations. Together, these results show that GABABRs on cortico-bulbar afferents gate excitatory transmission in a target-specific manner and thus shape how the OB integrates sensory inputs and top-down information. The olfactory bulb (OB) receives top-down inputs from the olfactory cortex that produce direct excitation and feedforward inhibition onto mitral and tufted cells, the principal neurons. The functional role of this feedback and the mechanisms regulating the balance of feedback excitation and inhibition remain unknown. We found that GABAB receptors are

  5. Role of olfactory bulb serotonin in olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae).

    Science.gov (United States)

    Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Haupt, Moritz; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2010-09-17

    The role of olfactory bulb (OB) serotonin [5-hydroxytryptamine (5-HT)] in olfactory learning and memory was tested in the greater short-nosed fruit bat, Cynopterus sphinx (family Pteropodidae). Graded concentrations (25, 40, and 60microg) of 5,7-dihydroxytryptamine (5,7-DHT) or saline were injected into the OB of bats one day before training to the novel odor. In a behavioral test, 5,7-DHT (60microg) injected bats made significantly fewer feeding attempts and bouts when compared to saline-injected bats during learning and in the memory test. Subsequent biochemical analysis showed that 5-HT level was effectively depleted in the OB of 5,7-DHT injected bats. To test odor-induced 5-HT mediated changes in 5-HT receptors and second messenger cascade in the OB, we examined the expression of 5-HT receptors and mitogen-activated protein kinase (MAPK)/Erk cascade after training to the novel odor. We found that odor stimulation up-regulated the expression of 5-HT(1A) receptor, Erk1 and Creb1 mRNA, and phosphorylation of ERK1 and CREB1. Odor stimulation failed to induce expression in 5-HT-depleted bats, which is similar to control bats and significantly low compared to saline-treated bats. Together these data revealed that the level of 5-HT in the OB may regulate olfactory learning and memory in C. sphinx through Erk and CREB.

  6. NCAM and Thy-1 in special sense organs of the developing mouse.

    Science.gov (United States)

    Terkelsen, O B; Bock, E; Møllgård, K

    1989-01-01

    The distribution of the neural cell adhesion molecule (NCAM) and Thy-1 in the olfactory mucosa and olfactory bulb, the eye and the inner ear was examined with immunocytochemistry in mouse embryos from embryonic day 12 (E 12) to embryonic day 19 (E 19). In general, neurons are completely outlined with NCAM, whereas Thy-1 outlines only dendrites and axons. A variable cytoplasmic staining for Thy-1 is present in the perikarya. Neurons directly associated with special sense organs express NCAM and Thy-1 already from the earliest stage and throughout the period investigated, apart from the olfactory neurons in which Thy-1 disappears at E 19. The mitral cells in the olfactory bulb show Thy-1 but no NCAM reactivity. In the eye, lens fibers express Thy-1 and the pigmented layer expresses NCAM; neither of the two molecules can be detected at E 19. In the inner ear, hair cells express NCAM at E 19. Based on the distribution during the developmental period studied and on the cellular localisation of reaction products, it is suggested that the NCAM adhesion function could be of a more general nature by keeping appropriate cell membranes in close contact and thereby allowing more specific molecular interactions to take place. Thy-1, which is located on dendrites and axons, could be such a specific factor and function as recognition molecule in the developing nervous system.

  7. fMRI study of the role of glutamate NMDA receptor in the olfactory adaptation in rats: Insights into cellular and molecular mechanisms of olfactory adaptation.

    Science.gov (United States)

    Zhao, Fuqiang; Wang, Xiaohai; Zariwala, Hatim A; Uslaner, Jason M; Houghton, Andrea K; Evelhoch, Jeffrey L; Hostetler, Eric; Winkelmann, Christopher T; Hines, Catherine D G

    2017-04-01

    Olfactory adaptation, characterized by attenuation of response to repeated odor stimulations or continuous odor exposure, is an intrinsic feature of olfactory processing. Adaptation can be induced by either "synaptic depression" due to depletion of neurotransmitters, or "enhanced inhibition" onto principle neurons by local inhibitory interneurons in olfactory structures. It is not clear which mechanism plays a major role in olfactory adaptation. More importantly, molecular sources of enhanced inhibition have not been identified. In this study, olfactory responses to either repeated 40-s stimulations with interstimulus intervals (ISI) of 14