Olfactory perception of chemically diverse molecules.

PubMed

Keller, Andreas; Vosshall, Leslie B

2016-08-08

Understanding the relationship between a stimulus and how it is perceived reveals fundamental principles about the mechanisms of sensory perception. While this stimulus-percept problem is mostly understood for color vision and tone perception, it is not currently possible to predict how a given molecule smells. While there has been some progress in predicting the pleasantness and intensity of an odorant, perceptual data for a larger number of diverse molecules are needed to improve current predictions. Towards this goal, we tested the olfactory perception of 480 structurally and perceptually diverse molecules at two concentrations using a panel of 55 healthy human subjects. For each stimulus, we collected data on perceived intensity, pleasantness, and familiarity. In addition, subjects were asked to apply 20 semantic odor quality descriptors to these stimuli, and were offered the option to describe the smell in their own words. Using this dataset, we replicated several previous correlations between molecular features of the stimulus and olfactory perception. The number of sulfur atoms in a molecule was correlated with the odor quality descriptors "garlic," "fish," and "decayed," and large and structurally complex molecules were perceived to be more pleasant. We discovered a number of correlations in intensity perception between molecules. We show that familiarity had a strong effect on the ability of subjects to describe a smell. Many subjects used commercial products to describe familiar odorants, highlighting the role of prior experience in verbal reports of olfactory perception. Nonspecific descriptors like "chemical" were applied frequently to unfamiliar odorants, and unfamiliar odorants were generally rated as neither pleasant nor unpleasant. We present a very large psychophysical dataset and use this to correlate molecular features of a stimulus to olfactory percept. Our work reveals robust correlations between molecular features and perceptual qualities, and

The effect of cholesterol on the partitioning of 1-octanol into POPC vesicles

NASA Astrophysics Data System (ADS)

Zakariaee Kouchaksaraee, Roja

Microcalorimetry has become a method of choice for sensitive characterization of biomolecular interactions. In this study, isothermal titration calorimetry (ITC) was used to measure the partitioning of 1-octanol into lipid bilayers composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), a semi-unsaturated lipid, and cholesterol, a steroid, as a function of cholesterol molar concentration. The ITC instrument measures the heat evolved or absorbed upon titration of a liposome dispersion, at concentrations ranging from 0 to 40% cholesterol, into a suspension of 1-octanol in water. A model function was fit to the data in order to determine the partition coefficient of octanol into POPC bilayers and the enthalpy of interaction. I found that the partition coefficient increases and the heat of interaction becomes less negative with increasing cholesterol content, in contrast to results found by other groups for partitioning of alcohols into lipid-cholesterol bilayers containing saturated lipids. The heat of dilution of vesicles was also measured. Keywords: Partition coefficient; POPC; 1-Octanol; Cholesterol; Isothermal titration calorimetry; Lipid-alcohol interactions. Subject Terms: Calorimetry; Membranes (Biology); Biophysics; Biology -- Technique; Bilayer lipid membranes -- Biotechnology; Lipid membranes -- Biotechnology.

Norepinephrine and Learning-Induced Plasticity in Infant Rat Olfactory System

PubMed Central

Sullivan, Regina M.; Wilson, Donald A.; Leon, Michael

2007-01-01

Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE β-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE β-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucase (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-lsoproterenol-Propranolol, or (3) Odor only-lsoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. PMID:2585063

Short-term memory in olfactory network dynamics

NASA Astrophysics Data System (ADS)

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.

Olfactory Blocking and Odorant Similarity in the Honeybee

ERIC Educational Resources Information Center

Gerber, Bertram; Giurfa, Martin; Guerrieri, Fernando; Lachnit, Harald

2005-01-01

Blocking occurs when previous training with a stimulus A reduces (blocks) subsequent learning about a stimulus B, when A and B are trained in compound. The question of whether blocking exists in olfactory conditioning of proboscis extension reflex (PER) in honeybees is under debate. The last published accounts on blocking in honeybees state that…

Temporal Response Properties of Accessory Olfactory Bulb Neurons: Limitations and Opportunities for Decoding.

PubMed

Yoles-Frenkel, Michal; Kahan, Anat; Ben-Shaul, Yoram

2018-05-23

The vomeronasal system (VNS) is a major vertebrate chemosensory system that functions in parallel to the main olfactory system (MOS). Despite many similarities, the two systems dramatically differ in the temporal domain. While MOS responses are governed by breathing and follow a subsecond temporal scale, VNS responses are uncoupled from breathing and evolve over seconds. This suggests that the contribution of response dynamics to stimulus information will differ between these systems. While temporal dynamics in the MOS are widely investigated, similar analyses in the accessory olfactory bulb (AOB) are lacking. Here, we have addressed this issue using controlled stimulus delivery to the vomeronasal organ of male and female mice. We first analyzed the temporal properties of AOB projection neurons and demonstrated that neurons display prolonged, variable, and neuron-specific characteristics. We then analyzed various decoding schemes using AOB population responses. We showed that compared with the simplest scheme (i.e., integration of spike counts over the entire response period), the division of this period into smaller temporal bins actually yields poorer decoding accuracy. However, optimal classification accuracy can be achieved well before the end of the response period by integrating spike counts within temporally defined windows. Since VNS stimulus uptake is variable, we analyzed decoding using limited information about stimulus uptake time, and showed that with enough neurons, such time-invariant decoding is feasible. Finally, we conducted simulations that demonstrated that, unlike the main olfactory bulb, the temporal features of AOB neurons disfavor decoding with high temporal accuracy, and, rather, support decoding without precise knowledge of stimulus uptake time. SIGNIFICANCE STATEMENT A key goal in sensory system research is to identify which metrics of neuronal activity are relevant for decoding stimulus features. Here, we describe the first systematic

Preparation and characterization of magnetorheological fluids by dispersion of carbonyl iron microparticles in PAO/1-octanol

NASA Astrophysics Data System (ADS)

Morillas, Jose R.; Bombard, Antonio J. F.; de Vicente, Juan

2016-01-01

This work reports an investigation into the effect of 1-octanol concentration in the formulation of concentrated polyalphaolefin-based magnetorheological fluids. Special emphasis is paid to the understanding of their kinetic stability and redispersibility characteristics in the ‘off-state’ (absence of magnetic field). Techniques employed involve light scattering, electroacoustics and rheometry, using a vane tool, to precisely determine the yield value. The results obtained show a minimum in the rheological material functions for 1-octanol concentrations within the range 0.5-5.0 wt%. This finding is tentatively explained in terms of the potential energy of interaction between the dispersed particles as a result of the formation of 1-octanol micelles in good agreement with Bombard and Dukhin (2014 Langmuir 30 4517-21).

Determination of 1-octanol-air partition coefficient using gaseous diffusion in the air boundary layer.

PubMed

Ha, Yeonjeong; Kwon, Jung-Hwan

2010-04-15

Exact determination of the partition coefficient between 1-octanol and air (K(OA)) is very important because it is a key descriptor for describing the thermodynamic partitioning between the air and organic phases. In spite of its importance, the number and quality of experimental K(OA) values for hydrophobic organic chemicals are limited because of experimental difficulties. Thus, to measure K(OA) values, a high-throughput method was developed that used liquid-phase extraction with 1-octanol drop at the tip of a microsyringe needle. The concentration in the headspace surrounding the 1 muL octanol drop was equilibrated with liquid octanol containing polycyclic aromatic hydrocarbons (PAHs). The change in concentrations of PAHs in the octanol drop was measured to obtain mass transfer rate constants, and these rate constants were then converted into K(OA) values using a film diffusion model. Thirteen polycyclic aromatic hydrocarbons with log K(OA) between 5 and 12 were chosen for the proof of the principle. Experimental determination of log K(OA) was accomplished in 30 h for PAHs with their log K(OA) less than 11. The measured log K(OA) values were very close to those obtained by various experimental and estimation methods in the literature, suggesting that this new method can provide a fast and easy determination of log K(OA) values for many chemicals of environmental interests. In addition, the applicability of the method can be extended to determine Henry's law constant for compounds with low vapor pressure and to estimate gaseous transfer rate of semivolatile compounds for environmental fate modeling.

Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila.

PubMed

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.

Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

PubMed Central

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

Molecular Mechanisms of Olfactory Responses to Stimulus Mixtures

DTIC Science & Technology

1991-02-26

demonstrated that the amino acid chemoreceptors in this organism are function- ally coupled to one or more G-proteins (19). Biochemical studies have also shown...Hwang, P.M. and Pevsner, J. (1989) Molecular mechanisms of olfaction. TINS 12, 35-38. 3. Bruch, R.C. (1990) Signal transduction in olfaction and taste ...amino acid olfactory receptor. Comp. Biochem. Physiol. 91B, 535-540. 17. Caprio, J. (1978) Olfaction and taste in the channel catfish: An

Appetitive but Not Aversive Olfactory Conditioning Modifies Antennal Movements in Honeybees

ERIC Educational Resources Information Center

Cholé, Hanna; Junca, Pierre; Sandoz, Jean-Christophe

2015-01-01

In honeybees, two olfactory conditioning protocols allow the study of appetitive and aversive Pavlovian associations. Appetitive conditioning of the proboscis extension response (PER) involves associating an odor, the conditioned stimulus (CS) with a sucrose solution, the unconditioned stimulus (US). Conversely, aversive conditioning of the sting…

Role of a Ubiquitously Expressed Receptor in the Vertebrate Olfactory System

PubMed Central

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

2013-01-01

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. PMID:24048853

Olfactory bulb gamma oscillations are enhanced with task demands.

PubMed

Beshel, Jennifer; Kopell, Nancy; Kay, Leslie M

2007-08-01

Fast oscillations in neural assemblies have been proposed as a mechanism to facilitate stimulus representation in a variety of sensory systems across animal species. In the olfactory system, intervention studies suggest that oscillations in the gamma frequency range play a role in fine odor discrimination. However, there is still no direct evidence that such oscillations are intrinsically altered in intact systems to aid in stimulus disambiguation. Here we show that gamma oscillatory power in the rat olfactory bulb during a two-alternative choice task is modulated in the intact system according to task demands with dramatic increases in gamma power during discrimination of molecularly similar odorants in contrast to dissimilar odorants. This elevation in power evolves over the course of criterion performance, is specific to the gamma frequency band (65-85 Hz), and is independent of changes in the theta or beta frequency band range. Furthermore, these high amplitude gamma oscillations are restricted to the olfactory bulb, such that concurrent piriform cortex recordings show no evidence of enhanced gamma power during these high-amplitude events. Our results display no modulation in the power of beta oscillations (15-28 Hz) shown previously to increase with odor learning in a Go/No-go task, and we suggest that the oscillatory profile of the olfactory system may be influenced by both odor discrimination demands and task type. The results reported here indicate that enhancement of local gamma power may reflect a switch in the dynamics of the system to a strategy that optimizes stimulus resolution when input signals are ambiguous.

Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment.

PubMed

Huart, Caroline; Rombaux, Philippe; Gérard, Thomas; Hanseeuw, Bernard; Lhommel, Renaud; Quenon, Lisa; Ivanoiu, Adrian; Mouraux, André

2015-01-01

Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

It takes two-coincidence coding within the dual olfactory pathway of the honeybee.

PubMed

Brill, Martin F; Meyer, Anneke; Rössler, Wolfgang

2015-01-01

To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code).

Olfactory cortical adaptation facilitates detection of odors against background.

PubMed

Kadohisa, Mikiko; Wilson, Donald A

2006-03-01

Detection and discrimination of odors generally, if not always, occurs against an odorous background. On any given inhalation, olfactory receptor neurons will be activated by features of both the target odorant and features of background stimuli. To identify a target odorant against a background therefore, the olfactory system must be capable of grouping a subset of features into an odor object distinct from the background. Our previous work has suggested that rapid homosynaptic depression of afferents to the anterior piriform cortex (aPCX) contributes to both cortical odor adaptation to prolonged stimulation and habituation of simple odor-evoked behaviors. We hypothesize here that this process may also contribute to figure-ground separation of a target odorant from background stimulation. Single-unit recordings were made from both mitral/tufted cells and aPCX neurons in urethan-anesthetized rats and mice. Single-unit responses to odorant stimuli and their binary mixtures were determined. One of the odorants was randomly selected as the background and presented for 50 s. Forty seconds after the onset of the background stimulus, the second target odorant was presented, producing a binary mixture. The results suggest that mitral/tufted cells continue to respond to the background odorant and, when the target odorant is presented, had response magnitudes similar to that evoked by the binary mixture. In contrast, aPCX neurons filter out the background stimulus while maintaining responses to the target stimulus. Thus the aPCX acts as a filter driven most strongly by changing stimuli, providing a potential mechanism for olfactory figure-ground separation and selective reading of olfactory bulb output.

An engineered fatty acid synthase combined with a carboxylic acid reductase enables de novo production of 1-octanol in Saccharomyces cerevisiae.

PubMed

Henritzi, Sandra; Fischer, Manuel; Grininger, Martin; Oreb, Mislav; Boles, Eckhard

2018-01-01

The ideal biofuel should not only be a regenerative fuel from renewable feedstocks, but should also be compatible with the existing fuel distribution infrastructure and with normal car engines. As the so-called drop-in biofuel, the fatty alcohol 1-octanol has been described as a valuable substitute for diesel and jet fuels and has already been produced fermentatively from sugars in small amounts with engineered bacteria via reduction of thioesterase-mediated premature release of octanoic acid from fatty acid synthase or via a reversal of the β-oxidation pathway. The previously engineered short-chain acyl-CoA producing yeast Fas1 R1834K /Fas2 fatty acid synthase variant was expressed together with carboxylic acid reductase from Mycobacterium marinum and phosphopantetheinyl transferase Sfp from Bacillus subtilis in a Saccharomyces cerevisiae Δfas1 Δfas2 Δfaa2 mutant strain. With the involvement of endogenous thioesterases, alcohol dehydrogenases, and aldehyde reductases, the synthesized octanoyl-CoA was converted to 1-octanol up to a titer of 26.0 mg L -1 in a 72-h fermentation. The additional accumulation of 90 mg L -1 octanoic acid in the medium indicated a bottleneck in 1-octanol production. When octanoic acid was supplied externally to the yeast cells, it could be efficiently converted to 1-octanol indicating that re-uptake of octanoic acid across the plasma membrane is not limiting. Additional overexpression of aldehyde reductase Ahr from Escherichia coli nearly completely prevented accumulation of octanoic acid and increased 1-octanol titers up to 49.5 mg L -1 . However, in growth tests concentrations even lower than 50.0 mg L -1 turned out to be inhibitory to yeast growth. In situ extraction in a two-phase fermentation with dodecane as second phase did not improve growth, indicating that 1-octanol acts inhibitive before secretion. Furthermore, 1-octanol production was even reduced, which results from extraction of the intermediate octanoic acid to

Effect of Flumethrin on Survival and Olfactory Learning in Honeybees

PubMed Central

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. PMID:23785490

Octanol-assisted liposome assembly on chip

PubMed Central

Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

2016-01-01

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5–20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells. PMID:26794442

Octanol-assisted liposome assembly on chip.

PubMed

Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E C; Dekker, Cees

2016-01-22

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

Octanol-assisted liposome assembly on chip

NASA Astrophysics Data System (ADS)

Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

2016-01-01

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

Cross-modal interaction between visual and olfactory learning in Apis cerana.

PubMed

Zhang, Li-Zhen; Zhang, Shao-Wu; Wang, Zi-Long; Yan, Wei-Yu; Zeng, Zhi-Jiang

2014-10-01

The power of the small honeybee brain carrying out behavioral and cognitive tasks has been shown repeatedly to be highly impressive. The present study investigates, for the first time, the cross-modal interaction between visual and olfactory learning in Apis cerana. To explore the role and molecular mechanisms of cross-modal learning in A. cerana, the honeybees were trained and tested in a modified Y-maze with seven visual and five olfactory stimulus, where a robust visual threshold for black/white grating (period of 2.8°-3.8°) and relatively olfactory threshold (concentration of 50-25%) was obtained. Meanwhile, the expression levels of five genes (AcCREB, Acdop1, Acdop2, Acdop3, Actyr1) related to learning and memory were analyzed under different training conditions by real-time RT-PCR. The experimental results indicate that A. cerana could exhibit cross-modal interactions between visual and olfactory learning by reducing the threshold level of the conditioning stimuli, and that these genes may play important roles in the learning process of honeybees.

Enhanced olfactory sensitivity in autism spectrum conditions.

PubMed

Ashwin, Chris; Chapman, Emma; Howells, Jessica; Rhydderch, Danielle; Walker, Ian; Baron-Cohen, Simon

2014-01-01

People with autism spectrum conditions (ASC) report heightened olfaction. Previous sensory experiments in people with ASC have reported hypersensitivity across visual, tactile, and auditory domains, but not olfaction. The aims of the present study were to investigate olfactory sensitivity in ASC, and to test the association of sensitivity to autistic traits. We recruited 17 adult males diagnosed with ASC and 17 typical adult male controls and tested their olfactory sensitivity using the Alcohol Sniff Test (AST), a standardised clinical evaluation of olfactory detection. The AST involves varying the distance between subject and stimulus until an odour is barely detected. Participants with ASC also completed the Autism Spectrum Quotient (AQ) as a measure of autism traits. The ASC group detected the odour at a mean distance of 24.1 cm (SD =11.5) from the nose, compared to the control group, who detected it at a significantly shorter mean distance of 14.4 cm (SD =5.9). Detection distance was independent of age and IQ for both groups, but showed a significant positive correlation with autistic traits in the ASC group (r =0.522). This is the first experimental demonstration, as far as the authors are aware, of superior olfactory perception in ASC and showing that greater olfactory sensitivity is correlated with a higher number of autistic traits. This is consistent with results from previous findings showing hypersensitivity in other sensory domains and may help explain anecdotal and questionnaire accounts of heightened olfactory sensitivity in ASC. Results are discussed in terms of possible underlying neurophysiology.

Olfactory Dysfunction in Patients With CNGB1-Associated Retinitis Pigmentosa.

PubMed

Charbel Issa, Peter; Reuter, Peggy; Kühlewein, Laura; Birtel, Johannes; Gliem, Martin; Tropitzsch, Anke; Whitcroft, Katherine L; Bolz, Hanno J; Ishihara, Kenji; MacLaren, Robert E; Downes, Susan M; Oishi, Akio; Zrenner, Eberhart; Kohl, Susanne; Hummel, Thomas

2018-05-24

Co-occurrence of retinitis pigmentosa (RP) and olfactory dysfunction may have a common genetic cause. To report olfactory function and the retinal phenotype in patients with biallelic mutations in CNGB1, a gene coding for a signal transduction channel subunit expressed in rod photoreceptors and olfactory sensory neurons. This case series was conducted from August 2015 through July 2017. The setting was a multicenter study involving 4 tertiary referral centers for inherited retinal dystrophies. Participants were 9 patients with CNGB1-associated RP. Results of olfactory testing, ocular phenotyping, and molecular genetic testing using targeted next-generation sequencing. Nine patients were included in the study, 3 of whom were female. Their ages ranged between 34 and 79 years. All patients had an early onset of night blindness but were usually not diagnosed as having RP before the fourth decade because of slow retinal degeneration. Retinal features were characteristic of a rod-cone dystrophy. Olfactory testing revealed reduced or absent olfactory function, with all except one patient scoring in the lowest quartile in relation to age-related norms. Brain magnetic resonance imaging and electroencephalography measurements in response to olfactory stimulation were available for 1 patient and revealed no visible olfactory bulbs and reduced responses to odor, respectively. Molecular genetic testing identified 5 novel (c.1312C>T, c.2210G>A, c.2492+1G>A, c.2763C>G, and c.3044_3050delGGAAATC) and 5 previously reported mutations in CNGB1. Mutations in CNGB1 may cause an autosomal recessive RP-olfactory dysfunction syndrome characterized by a slow progression of retinal degeneration and variable anosmia or hyposmia.

Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb.

PubMed

Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E

2013-08-21

Animals modulate their courtship and territorial behaviors in response to olfactory cues produced by other animals. In rodents, detecting these cues is the primary role of the accessory olfactory system (AOS). We sought to systematically investigate the natural stimulus coding logic and robustness in neurons of the first two stages of accessory olfactory processing, the vomeronasal organ (VNO) and accessory olfactory bulb (AOB). We show that firing rate responses of just a few well-chosen mouse VNO or AOB neurons can be used to reliably encode both sex and strain of other mice from cues contained in urine. Additionally, we show that this population code can generalize to new concentrations of stimuli and appears to represent stimulus identity in terms of diverging paths in coding space. Together, the results indicate that firing rate code on the temporal order of seconds is sufficient for accurate classification of pheromonal patterns at different concentrations and may be used by AOS neural circuitry to discriminate among naturally occurring urine stimuli.

Unitary Responses in Frog Olfactory Epithelium to Sterically Related Molecules at Low Concentrations

PubMed Central

Getchell, Thomas V.

1974-01-01

Responses of receptor cells in the frog's olfactory epithelium were recorded using platinum-black metal-filled microelectrodes. Spontaneous activity varied over a wide range from 0.07 to 1.8 spikes/s. Mean interspike intervals ranged from 13.7 to 0.5 s. Excitatory responses to six sterically related compounds at low concentrations were investigated. Stimuli were delivered in an aqueous medium. Thresholds for impulse initiation varied from greater than 1 mM down to the nanomolar concentration range. Thresholds of different olfactory receptors to the same stimulus could vary by several log units. Thresholds of the same receptor cell to different stimuli could be within the same order of magnitude, or could vary by as much as 5 log units. Based upon quantitative measures of stimulus-evoked excitatory responses it appeared that some receptors did not discriminate among sterically related molecules, whereas other receptors clearly discriminated between stimuli which evoke similar odor sensations. PMID:4211101

1-Octanol, a self-inhibitor of spore germination in Penicillium camemberti.

PubMed

Gillot, Guillaume; Decourcelle, Nicolas; Dauer, Gaëlle; Barbier, Georges; Coton, Emmanuel; Delmail, David; Mounier, Jérôme

2016-08-01

Penicillium camemberti is a technologically relevant fungus used to manufacture mold-ripened cheeses. This fungal species produces many volatile organic compounds (VOCs) including ammonia, methyl-ketones, alcohols and esters. Although it is now well known that VOCs can act as signaling molecules, nothing is known about their involvement in P. camemberti lifecycle. In this study, spore germination was shown to be self-regulated by quorum sensing in P. camemberti. This phenomenon, also called "crowding effect", is population-dependent (i.e. observed at high population densities). After determining the volatile nature of the compounds involved in this process, 1-octanol was identified as the main compound produced at high-spore density using GC-MS. Its inhibitory effect was confirmed in vitro and 3 mM 1-octanol totally inhibited spore germination while 100 μM only transiently inhibited spore germination. This is the first time that self-inhibition of spore germination is demonstrated in P. camemberti. The obtained results provide interesting perspectives for better control of mold-ripened cheese processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Computational prediction of ionic liquid 1-octanol/water partition coefficients.

PubMed

Kamath, Ganesh; Bhatnagar, Navendu; Baker, Gary A; Baker, Sheila N; Potoff, Jeffrey J

2012-04-07

Wet 1-octanol/water partition coefficients (log K(ow)) predicted for imidazolium-based ionic liquids using adaptive bias force-molecular dynamics (ABF-MD) simulations lie in excellent agreement with experimental values. These encouraging results suggest prospects for this computational tool in the a priori prediction of log K(ow) values of ionic liquids broadly with possible screening implications as well (e.g., prediction of CO(2)-philic ionic liquids).

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

PubMed

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.

Octanol-water distribution of engineered nanomaterials.

PubMed

Hristovski, Kiril D; Westerhoff, Paul K; Posner, Jonathan D

2011-01-01

The goal of this study was to examine the effects of pH and ionic strength on octanol-water distribution of five model engineered nanomaterials. Distribution experiments resulted in a spectrum of three broadly classified scenarios: distribution in the aqueous phase, distribution in the octanol, and distribution into the octanol-water interface. Two distribution coefficients were derived to describe the distribution of nanoparticles among octanol, water and their interface. The results show that particle surface charge, surface functionalization, and composition, as well as the solvent ionic strength and presence of natural organic matter, dramatically impact this distribution. Distributions of nanoparticles into the interface were significant for nanomaterials that exhibit low surface charge in natural pH ranges. Increased ionic strengths also contributed to increased distributions of nanoparticle into the interface. Similarly to the octanol-water distribution coefficients, which represent a starting point in predicting the environmental fate, bioavailability and transport of organic pollutants, distribution coefficients such as the ones described in this study could help to easily predict the fate, bioavailability, and transport of engineered nanomaterials in the environment.

Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.

PubMed

Rey, Nolwen L; Jardanhazi-Kurutz, Daniel; Terwel, Dick; Kummer, Markus P; Jourdan, Francois; Didier, Anne; Heneka, Michael T

2012-02-01

Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits. Copyright © 2012 Elsevier Inc. All rights reserved.

Accelerated age-related olfactory decline among type 1 Usher patients.

PubMed

Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D

2016-06-22

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin' Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome.

Flavor-Intensity Perception: Effects of Stimulus Context

PubMed Central

Marks, Lawrence E.; Shepard, Timothy G.; Burger, Kelly; Chakwin, Emily M.

2011-01-01

Stimulus context affects judgments of intensity of both gustatory and olfactory flavors, and the contextual effects are modality-specific. Does context also exert separate effects on the gustatory and olfactory components of flavor mixtures? To answer this question, in each of 4 experiments, subjects rated the perceived intensity of 16 mixtures constructed by combining 4 concentrations of the gustatory flavorant sucrose with 4 concentrations of the retronasal olfactory flavorant citral. In 1 contextual condition of each experiment, concentrations of sucrose were relatively high and those of citral low; in the other condition, the relative concentrations of sucrose and citral reversed. There were 2 main results: First, consistent with earlier findings, in 5 of the 8 conditions, the ratings were consistent with linear addition of perceived sucrose and citral; departures from additivity appeared, however, in 3 conditions where the relative concentrations of citral were high. Second, changes in context produced contrast (adaptation-like changes) in perceived intensity: The contribution to perceived intensity of a given concentration of a flavorant was smaller when the contextual concentrations of that flavorant were high rather than low. A notable exception was the absence of contextual effects on the perceived intensity of near-threshold citral. These findings suggest that the contextual effects may arise separately in the gustatory and olfactory channels, prior to the integration of perceived flavor intensity. PMID:21930139

Solvation of decane and benzene in mixtures of 1-octanol and N, N-dimethylformamide

NASA Astrophysics Data System (ADS)

Kustov, A. V.; Smirnova, N. L.

2016-09-01

The heats of dissolution of decane and benzene in a model system of octanol-1 (OctOH) and N, N-dimethylformamide (DMF) at 308 K are measured using a variable temperature calorimeter equipped with an isothermal shell. Standard enthalpies are determined and standard heat capacities of dissolution in the temperature range of 298-318 K are calculated using data obtained in [1, 2]. The state of hydrocarbon molecules in a binary mixture is studied in terms of the enhanced coordination model (ECM). Benzene is shown to be preferentially solvated by DMF over the range of physiological temperatures. The solvation shell of decane is found to be strongly enriched with 1-octanol. It is obvious that although both hydrocarbons are nonpolar, the presence of the aromatic π-system in benzene leads to drastic differences in their solvation in a lipid-protein medium.

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

ERIC Educational Resources Information Center

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…

Sensory memory for odors is encoded in spontaneous correlated activity between olfactory glomeruli.

PubMed

Galán, Roberto F; Weidert, Marcel; Menzel, Randolf; Herz, Andreas V M; Galizia, C Giovanni

2006-01-01

Sensory memory is a short-lived persistence of a sensory stimulus in the nervous system, such as iconic memory in the visual system. However, little is known about the mechanisms underlying olfactory sensory memory. We have therefore analyzed the effect of odor stimuli on the first odor-processing network in the honeybee brain, the antennal lobe, which corresponds to the vertebrate olfactory bulb. We stained output neurons with a calcium-sensitive dye and measured across-glomerular patterns of spontaneous activity before and after a stimulus. Such a single-odor presentation changed the relative timing of spontaneous activity across glomeruli in accordance with Hebb's theory of learning. Moreover, during the first few minutes after odor presentation, correlations between the spontaneous activity fluctuations suffice to reconstruct the stimulus. As spontaneous activity is ubiquitous in the brain, modifiable fluctuations could provide an ideal substrate for Hebbian reverberations and sensory memory in other neural systems.

Accelerated age-related olfactory decline among type 1 Usher patients

PubMed Central

Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

2016-01-01

Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

Successful acquisition of an olfactory discrimination test by Asian elephants, Elephas maximus.

PubMed

Arvidsson, Josefin; Amundin, Mats; Laska, Matthias

2012-02-01

The present study demonstrates that Asian elephants, Elephas maximus, can successfully be trained to cooperate in an olfactory discrimination test based on a food-rewarded two-alternative instrumental conditioning procedure. The animals learned the basic principle of the test within only 60 trials and readily mastered intramodal stimulus transfer tasks. Further, they were capable of distinguishing between structurally related odor stimuli and remembered the reward value of previously learned odor stimuli after 2, 4, 8, and 16 weeks of recess without any signs of forgetting. The precision and consistency of the elephants' performance in tests of odor discrimination ability and long-term odor memory demonstrate the suitability of this method for assessing olfactory function in this proboscid species. An across-species comparison of several measures of olfactory learning capabilities such as speed of initial task acquisition and ability to master intramodal stimulus transfer tasks shows that Asian elephants are at least as good in their performance as mice, rats, and dogs, and clearly superior to nonhuman primates and fur seals. The results support the notion that Asian elephants may use olfactory cues for social communication and food selection and that the sense of smell may play an important role in the control of their behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

A Behavioral and Genetic Dissection of Two Forms of Olfactory Plasticity in Caenorhabditis elegans: Adaptation and Habituation

PubMed Central

Bernhard, Nirit; van der Kooy, Derek

2000-01-01

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations. PMID:10940320

Egr-1 antisense oligodeoxynucleotide administration into the olfactory bulb impairs olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx.

PubMed

Ganesh, Ambigapathy; Bogdanowicz, Wieslaw; Balamurugan, Krishnaswamy; Ragu Varman, Durairaj; Rajan, Koilmani Emmanuvel

2012-08-30

Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We examined two important examples of these, calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95, in regard to the functional role of early growth response gene-1 (egr-1) in regulation of olfactory learning in the greater short-nosed fruit bat Cynopterus sphinx (family Pteropodidae). To test whether activation of egr-1 in the olfactory bulb (OB) is required for olfactory memory of these bats, bilaterally canulated individuals were infused with antisense (AS) or non-sense (NS)-oligodeoxynucleotides (ODN) of egr-1, or with phosphate buffer saline (PBS), 2h before the olfactory training. Our results showed that behavioral training significantly up-regulates immediate early gene (IEG) EGR-1 and key synaptic proteins Synaptotagmin-1(SYT-1), CaMKII and PSD-95, and phosphorylation of CaMKII in the OB at the protein level per se. Subsequently, we observed that egr-1 antisense-ODN infusion in the OB impaired olfactory memory and down regulates the expression of CaMKII and PSD-95, and the phosphorylation of CaMKII but not SYT-1. In contrast, NS-ODN or PBS had no effect on the expression of the PSDs CaMKII or PSD-95, or on the phosphorylation of CaMKII. When the egr-1 NS-ODN was infused in the OB after training for the novel odor there was no effect on olfactory memory. These findings suggest that egr-1 control the activation of CaMKII and PSD-95 during the process of olfactory memory formation. Copyright © 2012 Elsevier B.V. All rights reserved.

Directional coupling from the olfactory bulb to the hippocampus during a go/no-go odor discrimination task.

PubMed

Gourévitch, Boris; Kay, Leslie M; Martin, Claire

2010-05-01

The hippocampus and olfactory regions are anatomically close, and both play a major role in memory formation. However, the way they interact during odor processing is still unclear. In both areas, strong oscillations of the local field potential (LFP) can be recorded, and are modulated by behavior. In particular, in the olfactory system, the beta rhythm (15-35 Hz) is associated with cognitive processing of an olfactory stimulus. Using LFP recordings in the olfactory bulb and dorsal and ventral hippocampus during performance of an olfactory go/no-go task in rats, we previously showed that beta oscillations are also present in the hippocampus, coherent with those in the olfactory bulb, during odor sampling. In this study, we provide further insight into information transfer in the olfacto-hippocampal network by using directional coherence (DCOH estimate), a method based on the temporal relation between two or more signals in the frequency domain. In the theta band (6-12 Hz), coherence between the olfactory bulb (OB) and the hippocampus (HPC) is weak and can be both in the feedback and feedforward directions. However, at this frequency, modulation of the coupling between the dorsal and ventral hippocampus is seen during stimulus expectation versus odor processing. In the beta frequency band (15-35 Hz), analysis showed a strong unidirectional coupling from the OB to dorsal and ventral HPC, indicating that, during odor processing, beta oscillations in the hippocampus are driven by the olfactory bulb.

Olfactory memory formation and the influence of reward pathway during appetitive learning by honey bees.

PubMed

Wright, Geraldine A; Mustard, Julie A; Kottcamp, Sonya M; Smith, Brian H

2007-11-01

Animals possess the ability to assess food quality via taste and via changes in state that occur after ingestion. Here, we investigate the extent to which a honey bee's ability to assess food quality affected the formation of association with an odor stimulus and the retention of olfactory memories associated with reward. We used three different conditioning protocols in which the unconditioned stimulus (food) was delivered as sucrose stimulation to the proboscis (mouthparts), the antennae or to both proboscis and antennae. All means of delivery of the unconditioned stimulus produced robust associative conditioning with an odor. However, the memory of a conditioned odor decayed at a significantly greater rate for subjects experiencing antennal-only stimulation after either multiple- or single-trial conditioning. Finally, to test whether the act of feeding on a reward containing sucrose during conditioning affected olfactory memory formation, we conditioned honey bees to associate an odor with antennal stimulation with sucrose followed by feeding on a water droplet. We observed that a honey bee's ability to recall the conditioned odor was not significantly different from that of subjects conditioned with an antennal-only sucrose stimulus. Our results show that stimulation of the sensory receptors on the proboscis and/or ingestion of the sucrose reward during appetitive olfactory conditioning are necessary for long-term memory formation.

Nanostructures in n-Octanol Equilibrated with Additives and/or Water.

PubMed

Cevc, Gregor; Berts, Ida; Fischer, Stefan F; Rädler, Joachim O; Nickel, Bert

2018-05-29

Fluid fatty alcohols are believed to be nanostructured but broadly amorphous (i.e., noncrystalline) fluids and solvents, including the most popular fatty tissue mimetic, hydrated n-octanol (i.e., hydro-octanol). To check this premise, we studied dry octanol and hydro-octanol as a model of relatively short fluid n-alkanols with small-angle X-ray scattering (SAXS). We also combined this alkanol with the matching alkane (i.e., octane) and with a common anti-inflammatory pain killer (ketoprofen). This revealed that (hydro-)octanol and arguably any other short fatty alcohol form a mesophase. Its basic structural motif are regularly packed polar nanoclusters, reflected in the inner peak in the SAXS diffractogram of (hydro-)octanol and other fluid n-alkanols. The nanoclusters arguably resemble tiny, (inverse) hydrated bilayer fragments, located on a thermally smeared para-crystalline lattice. Additives to hydro-octanol can change the nanoclusters only moderately, if at all. For example, octane and the drug ketoprofen added to hydro-octanol enlarge the nanoclusters only little because of the mixture's packing frustration. To associate with and to bring more water into hydro-octanol, an additive must hence transform the nanoclusters: it expands them into irregularly distributed aqueous lacunae that form a proto-microemulsion, reflected in the previously unknown Guinier's SAXS signal. A "weak" (i.e., a weakly polar or nonpolar) additive can moreover create only size-limited lacunae. Coexistence of nanoclusters and lacunae as well as size variability of the latter in hydro-octanol subvert the concept of octanol-water partition coefficient, which relies on the studied compartment homogeneity. In turn, it opens new possibilities for interfacial catalysis. Reinterpreting "octanol-water partition coefficient" data in terms of octanol-water association or binding constant(s) could furthermore diminish the variability of molecular lipophilicity description and pave the ground

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron

PubMed Central

Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry. PMID:27163287

Morphogenetic Studies of the Drosophila DA1 Ventral Olfactory Projection Neuron.

PubMed

Shen, Hung-Chang; Wei, Jia-Yi; Chu, Sao-Yu; Chung, Pei-Chi; Hsu, Tsai-Chi; Yu, Hung-Hsiang

2016-01-01

In the Drosophila olfactory system, odorant information is sensed by olfactory sensory neurons and relayed from the primary olfactory center, the antennal lobe (AL), to higher olfactory centers via olfactory projection neurons (PNs). A major portion of the AL is constituted with dendrites of four groups of PNs, anterodorsal PNs (adPNs), lateral PNs (lPNs), lateroventral PNs (lvPNs) and ventral PNs (vPNs). Previous studies have been focused on the development and function of adPNs and lPNs, while the investigation on those of lvPNs and vPNs received less attention. Here, we study the molecular and cellular mechanisms underlying the morphogenesis of a putative male-pheromone responding vPN, the DA1 vPN. Using an intersection strategy to remove background neurons labeled within a DA1 vPN-containing GAL4 line, we depicted morphological changes of the DA1 vPN that occurs at the pupal stage. We then conducted a pilot screen using RNA interference knock-down approach to identify cell surface molecules, including Down syndrome cell adhesion molecule 1 and Semaphorin-1a, that might play essential roles for the DA1 vPN morphogenesis. Taken together, by revealing molecular and cellular basis of the DA1 vPN morphogenesis, we should provide insights into future comprehension of how vPNs are assembled into the olfactory neural circuitry.

No oral-cavity-only discrimination of purely olfactory odorants.

PubMed

Stephenson, Dejaimenay; Halpern, Bruce P

2009-02-01

The purely olfactory odorants coumarin, octanoic acid, phenylethyl alcohol, and vanillin had been found to be consistently identified when presented retronasally but could not be identified when presented oral-cavity only (OCO). However, OCO discrimination of these odorants was not tested. Consequently, it remained possible that the oral cavity trigeminal system might provide sufficient information to differentiate these purely olfactory odorants. To evaluate this, 20 participants attempted to discriminate vapor-phase coumarin, octanoic acid, phenylethyl alcohol, and vanillin and, as a control, the trigeminal stimulus peppermint extract, from their glycerin solvent, all presented OCO. None of the purely olfactory odorants could be discriminated OCO, but, as expected, peppermint extract was consistently discriminated. This inability to discriminate clarifies and expands the previous report of lack of OCO identification of purely olfactory odorants. Taken together with prior data, these results suggest that the oral cavity trigeminal system is fully unresponsive to these odorants in vapor phase and that coumarin, octanoic acid, phenylethyl alcohol, and vanillin are indeed purely olfactory stimuli. The OCO discrimination of peppermint extract demonstrated that the absence of discrimination for the purely olfactory odorants was odorant dependent and confirmed that the oral cavity trigeminal system will provide differential response information to some vapor-phase stimuli.

Time-course of trigeminal versus olfactory stimulation: evidence from chemosensory evoked potentials.

PubMed

Flohr, Elena L R; Boesveldt, Sanne; Haehner, Antje; Iannilli, Emilia; Sinding, Charlotte; Hummel, Thomas

2015-03-01

Habituation of responses to chemosensory signals has been explored in many ways. Strong habituation and adaptation processes can be observed at the various levels of processing. For example, with repeated exposure, amplitudes of chemosensory event-related potentials (ERP) decrease over time. However, long-term habituation has not been investigated so far and investigations of differences in habituation between trigeminal and olfactory ERPs are very rare. The present study investigated habituation over a period of approximately 80 min for two olfactory and one trigeminal stimulus, respectively. Habituation was examined analyzing the N1 and P2 amplitudes and latencies of chemosensory ERPs and intensity ratings. It was shown that amplitudes of both components - and intensity ratings - decreased from the first to the last block. Concerning ERP latencies no effects of habituation were seen. Amplitudes of trigeminal ERPs diminished faster than amplitudes of olfactory ERPs, indicating that the habituation of trigeminal ERPs is stronger than habituation of olfactory ERPs. Amplitudes of trigeminal ERPs were generally higher than amplitudes of olfactory ERPs, as it has been shown in various studies before. The results reflect relatively selective central changes in response to chemosensory stimuli over time. Copyright © 2015 Elsevier B.V. All rights reserved.

Changes in olfactory bulb volume following lateralized olfactory training.

PubMed

Negoias, S; Pietsch, K; Hummel, T

2017-08-01

Repeated exposure to odors modifies olfactory function. Consequently, "olfactory training" plays a significant role in hyposmia treatment. In addition, numerous studies show that the olfactory bulb (OB) volume changes in disorders associated with olfactory dysfunction. Aim of this study was to investigate whether and how olfactory bulb volume changes in relation to lateralized olfactory training in healthy people. Over a period of 4 months, 97 healthy participants (63 females and 34 males, mean age: 23.74 ± 4.16 years, age range: 19-43 years) performed olfactory training by exposing the same nostril twice a day to 4 odors (lemon, rose, eucalyptus and cloves) while closing the other nostril. Before and after olfactory training, magnetic resonance imaging (MRI) scans were performed to measure OB volume. Furthermore, participants underwent lateralized odor threshold and odor identification testing using the "Sniffin' Sticks" test battery.OB volume increased significantly after olfactory training (11.3 % and 13.1 % respectively) for both trained and untrained nostril. No significant effects of sex, duration and frequency of training or age of the subjects were seen. Interestingly, PEA odor thresholds worsened after training, while olfactory identification remained unchanged.These data show for the first time in humans that olfactory training may involve top-down process, which ultimately lead to a bilateral increase in olfactory bulb volume.

Integrating temperature with odor processing in the olfactory bulb.

PubMed

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.

Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis: implications for a hypothesis relating to mitogen-antimitogen opposition

NASA Technical Reports Server (NTRS)

Goto, T.; Takahashi, T.; Miyama, S.; Nowakowski, R. S.; Bhide, P. G.; Caviness, V. S. Jr

2002-01-01

Neocortical neurons arise from a pseudostratified ventricular epithelium (PVE) that lies within the ventricular zone (VZ) at the margins of the embryonic cerebral ventricles. We examined the effects of fibroblast growth factor-2 (FGF-2) and 1-octanol on cell output behavior of the PVE in explants of the embryonic mouse cerebral wall. FGF-2 is mitogenic and 1-octanol antimitogenic in the PVE. Whereas all postmitotic cells migrate out of the VZ in vivo, in the explants some postmitotic cells remain within the VZ. We refer to these cells as the indeterminate or I fraction, because they neither exit from the VZ nor reenter S phase as part of the proliferative (P) fraction. They are considered to be either in an extremely prolonged G(1) phase, unable to pass the G(1)/S transition, or in the G(0) state. The I fate choice is modulated by both FGF-2 and 1-octanol. FGF-2 decreased the I fraction and increased the P fraction. In contrast, 1-octanol increased the I fraction and nearly eliminated the P fraction. The effects of FGF-2 and 1-octanol were developmentally regulated, in that they were observed in the developmentally advanced lateral region of the cerebral wall but not in the medial region. Copyright 2002 Wiley-Liss, Inc.

Extractions of isoquinoline alkaloids with butanol and octanol.

PubMed

Gregorová, Jana; Babica, Jan; Marek, Radek; Paulová, Hana; Táborská, Eva; Dostál, Jirí

2010-09-01

Six different isoquinoline alkaloids (sanguinarine, chelerythrine, berberine, coptisine, allocryptopine, and protopine) were extracted by butanol and octanol from aqueous solution, pH 4.5. The samples were analyzed by HPLC. Butanol extraction was non-selective, alkaloids passed into organic phase in 83-98%. Octanol extraction provided more selective yields: sanguinarine 99%, chelerythrine 94%, berberine 18%, coptisine 16%, allocryptopine 7.5%, protopine 7%. Further, we tested octanol treatment of extract from Dicranostigma lactucoides. The octanol extraction yields were also selective: sanguinarine 98%, chelerythrine 92%, chelirubine 92.5%, protopine 6% and allocryptopine 3.5%. 6-Butoxy-5,6-dihydrosanguinarine and 6-butoxy-5,6-dihydrochelerythrine were prepared and their NMR and MS data are reported and discussed. Copyright (c) 2010 Elsevier B.V. All rights reserved.

The Adaptation of the Moth Pheromone Receptor Neuron to its Natural Stimulus

NASA Astrophysics Data System (ADS)

Kostal, Lubomir; Lansky, Petr; Rospars, Jean-Pierre

2008-07-01

We analyze the first phase of information transduction in the model of the olfactory receptor neuron of the male moth Antheraea polyphemus. We predict such stimulus characteristics that enable the system to perform optimally, i.e., to transfer as much information as possible. Few a priori constraints on the nature of stimulus and stimulus-to-signal transduction are assumed. The results are given in terms of stimulus distributions and intermittency factors which makes direct comparison with experimental data possible. Optimal stimulus is approximatelly described by exponential or log-normal probability density function which is in agreement with experiment and the predicted intermittency factors fall within the lowest range of observed values. The results are discussed with respect to electroantennogram measurements and behavioral observations.

Olfactory dysfunction affects thresholds to trigeminal chemosensory sensations.

PubMed

Frasnelli, J; Schuster, B; Hummel, T

2010-01-14

Next to olfaction and gustation, the trigeminal system represents a third chemosensory system. These senses are interconnected; a loss of olfactory function also leads to a reduced sensitivity in the trigeminal chemosensory system. However, most studies so far focused on comparing trigeminal sensitivity to suprathreshold stimuli; much less data is available with regard to trigeminal sensitivity in the perithreshold range. Therefore we assessed detection thresholds for CO(2), a relatively pure trigeminal stimulus in controls and in patients with olfactory dysfunction (OD). We could show that OD patients exhibit higher detection thresholds than controls. In addition, we were able to explore the effects of different etiologies of smell loss on trigeminal detection thresholds. We could show that in younger subjects, patients suffering from olfactory loss due to head trauma are more severely impaired with regard to their trigeminal sensitivity than patients with isolated congenital anosmia. In older patients, we could not observe any differences between different etiologies, probably due to the well known age-related decrease of trigeminal sensitivity. Furthermore we could show that a betterment of the OD was accompanied by decreased thresholds. This was most evident in patients with postviral OD. In conclusion, factors such as age, olfactory status and etiology of olfactory disorder can affect responsiveness to perithreshold trigeminal chemosensory stimuli. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Solubility of lovastatin in a family of six alcohols: Ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, and 1-octanol.

PubMed

Nti-Gyabaah, J; Chmielowski, R; Chan, V; Chiew, Y C

2008-07-09

Accurate experimental determination of solubility of active pharmaceutical ingredients (APIs) in solvents and its correlation, for solubility prediction, is essential for rapid design and optimization of isolation, purification, and formulation processes in the pharmaceutical industry. An efficient material-conserving analytical method, with in-line reversed HPLC separation protocol, has been developed to measure equilibrium solubility of lovastatin in ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, and 1-octanol between 279 and 313K. Fusion enthalpy DeltaH(fus), melting point temperature, Tm, and the differential molar heat capacity, DeltaC(P), were determined by differential scanning calorimetry (DSC) to be 43,136J/mol, 445.5K, and 255J/(molK), respectively. In order to use the regular solution equation, simplified assumptions have been made concerning DeltaC(P), specifically, DeltaC(P)=0, or DeltaC(P)=DeltaS. In this study, we examined the extent to which these assumptions influence the magnitude of the ideal solubility of lovastatin, and determined that both assumptions underestimate the ideal solubility of lovastatin. The solubility data was used with the calculated ideal solubility to obtain activity coefficients, which were then fitted to the van't Hoff-like regular solution equation. Examination of the plots indicated that both assumptions give erroneous excess enthalpy of solution, H(infinity), and hence thermodynamically inconsistent activity coefficients. The order of increasing ideality, or solubility of lovastatin was butanol>1-propanol>1-pentanol>1-hexanol>1-octanol.

Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone.

PubMed

Andersson, Heléne C; Anderson, Michelle F; Porritt, Michelle J; Nodin, Christina; Blomstrand, Fredrik; Nilsson, Michael

2011-07-01

Reactive gliosis and scar formation after brain injury can inhibit the recovery process. As many glial cells utilize gap junctions for intercellular signaling, this study investigated whether two commonly used gap junction blockers, octanol and carbenoxolone, could attenuate reactive gliosis following a minor traumatic brain injury. Octanol (710 mg/kg) or carbenoxolone (90 mg/kg) was administered 30 minutes before or after a needle track injury in adult male Sprague-Dawley rats. To mark dividing cells, animals were injected with bromodeoxyuridine (BrdU; 150 mg/kg) intraperitoneally two times per day, 8 hours apart and killed 2 days later. Immunohistochemistry for BrdU and markers for reactive glial cells [glial fibrillary acidic protein (GFAP), ED1, and NG2] were investigated using immunohistochemistry and western blot techniques. Two days after injury, increased cellular proliferation, activated astrocytes and microglia, and upregulation of NG2 expression were observed surrounding the injury site. Octanol and carbenoxolone administrated prior to injury significantly decreased cell proliferation by 60 and 70% respectively. The distance of GFAP immunoreactive astrocytes from the wound margin was decreased by 32 and 18% when octanol was administrated prior to or post injury respectively. Treatment with octanol also decreased the number of reactive microglia by 55% and, when administrated prior to injury, octanol reduced the distance of NG2 expression from the wound by 48%. The present study demonstrates that two important components of reactive gliosis, cellular activation and proliferation, can be attenuated by octanol and carbenoxolone.

Parallel processing via a dual olfactory pathway in the honeybee.

PubMed

Brill, Martin F; Rosenbaum, Tobias; Reus, Isabelle; Kleineidam, Christoph J; Nawrot, Martin P; Rössler, Wolfgang

2013-02-06

In their natural environment, animals face complex and highly dynamic olfactory input. Thus vertebrates as well as invertebrates require fast and reliable processing of olfactory information. Parallel processing has been shown to improve processing speed and power in other sensory systems and is characterized by extraction of different stimulus parameters along parallel sensory information streams. Honeybees possess an elaborate olfactory system with unique neuronal architecture: a dual olfactory pathway comprising a medial projection-neuron (PN) antennal lobe (AL) protocerebral output tract (m-APT) and a lateral PN AL output tract (l-APT) connecting the olfactory lobes with higher-order brain centers. We asked whether this neuronal architecture serves parallel processing and employed a novel technique for simultaneous multiunit recordings from both tracts. The results revealed response profiles from a high number of PNs of both tracts to floral, pheromonal, and biologically relevant odor mixtures tested over multiple trials. PNs from both tracts responded to all tested odors, but with different characteristics indicating parallel processing of similar odors. Both PN tracts were activated by widely overlapping response profiles, which is a requirement for parallel processing. The l-APT PNs had broad response profiles suggesting generalized coding properties, whereas the responses of m-APT PNs were comparatively weaker and less frequent, indicating higher odor specificity. Comparison of response latencies within and across tracts revealed odor-dependent latencies. We suggest that parallel processing via the honeybee dual olfactory pathway provides enhanced odor processing capabilities serving sophisticated odor perception and olfactory demands associated with a complex olfactory world of this social insect.

Intranasal Localizability of Odorants: Influence of Stimulus Volume

PubMed Central

Frasnelli, J.; Berg, J.; Huang, G.; Doty, R.L.

2011-01-01

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicyclate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a “relatively pure” olfactory stimulus. PMID:21310764

Intranasal localizability of odorants: influence of stimulus volume.

PubMed

Frasnelli, J; Hummel, T; Berg, J; Huang, G; Doty, R L

2011-05-01

When an odorant is presented to one side of the nose and air to the other, the ability to localize which side received the odorant depends upon trigeminal nerve stimulation. It has been shown that performance on this lateralization task increases as stimulus concentration increases. In this study, we determined the influences of stimulus volume and sex on the ability to localize each of 8 odorants presented at neat concentrations: anethole, geraniol, limonene, linalool, menthol, methyl salicylate, phenyl ethanol, and vanillin. At a low stimulus volume (11 mL), only menthol was localized at an above-chance level. At a high stimulus volume (21 mL), above-chance localization occurred for all odorants except vanillin. Women were significantly better than men in localizing menthol. Stimuli rated as most intense were those that were most readily localized. The detection performance measures, as well as rated intensity values, significantly correlated with earlier findings of the trigeminal detectability of odorants presented to anosmic and normosmic subjects. This study suggests that differences in stimulus volume may explain some discrepant findings within the trigeminal chemosensory literature and supports the concept that vanillin may be a "relatively pure" olfactory stimulus.

Response Times to Gustatory–Olfactory Flavor Mixtures: Role of Congruence

PubMed Central

Shepard, Timothy G.; Veldhuizen, Maria G.

2015-01-01

A mixture of perceptually congruent gustatory and olfactory flavorants (sucrose and citral) was previously shown to be detected faster than predicted by a model of probability summation that assumes stochastically independent processing of the individual gustatory and olfactory signals. This outcome suggests substantial integration of the signals. Does substantial integration also characterize responses to mixtures of incongruent flavorants? Here, we report simple response times (RTs) to detect brief pulses of 3 possible flavorants: monosodium glutamate, MSG (gustatory: “umami” quality), citral (olfactory: citrus quality), and a mixture of MSG and citral (gustatory–olfactory). Each stimulus (and, on a fraction of trials, water) was presented orally through a computer-operated, automated flow system, and subjects were instructed to press a button as soon as they detected any of the 3 non-water stimuli. Unlike responses previously found to the congruent mixture of sucrose and citral, responses here to the incongruent mixture of MSG and citral took significantly longer (RTs were greater) and showed lower detection rates than the values predicted by probability summation. This outcome suggests that the integration of gustatory and olfactory flavor signals is less extensive when the component flavors are perceptually incongruent rather than congruent, perhaps because incongruent flavors are less familiar. PMID:26304508

Octanol-air partition coefficients of polybrominated biphenyls.

PubMed

Hongxia, Zhao; Jingwen, Chen; Xie, Quan; Baocheng, Qu; Xinmiao, Liang

2009-03-01

The octanol-air partition coefficients (K(OA)) for PBB15, PBB26, PBB31, PBB49, PBB103 and PBB153 were determined as a function of temperature using a gas chromatographic retention time technique with 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (p,p'-DDT) as a reference substance. The internal energies of phase change from octanol to air (Delta(OA)U) were calculated for the six compounds and were in the range from 74 to 116 kJ mol(-1). Simple regression equations of log K(OA) versus relative retention times (RRTs) on gas chromatography (GC), and log K(OA) versus molecular connectivity indexes (MCI) were obtained, for which the correlation coefficients (r(2)) were greater than 0.985 at 283.15K and 298.15K. Thus the K(OA) values of the remaining PBBs can be predicted by using their RRTs and MCI according to these relationships.

Physicochemical properties/descriptors governing the solubility and partitioning of chemicals in water-solvent-gas systems. Part 1. Partitioning between octanol and air.

PubMed

Raevsky, O A; Grigor'ev, V J; Raevskaja, O E; Schaper, K-J

2006-06-01

QSPR analyses of a data set containing experimental partition coefficients in the three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have shown that it is possible to calculate any partition coefficient in the system 'gas phase/octanol/water' by three different approaches: (1) from experimental partition coefficients obtained in the corresponding two other subsystems. However, in many cases these data may not be available. Therefore, a solution may be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with polarisability alpha, a steric bulk effect descriptor) and supplemented with substructural indicator variables. (3) A very promising approach which is a combination of the similarity concept and QSPR based on HYBOT descriptors. In this approach observed partition coefficients of structurally nearest neighbours of a compound-of-interest are used. In addition, contributions arising from differences in alpha, SigmaCa, and SigmaCd values between the compound-of-interest and its nearest neighbour(s), respectively, are considered. In this investigation highly significant relationships were obtained by approaches (1) and (3) for the octanol/gas phase partition coefficient (log Log).

Retronasal odor representations in the dorsal olfactory bulb of rats

PubMed Central

Gautam, Shree Hari; Verhagen, Justus V.

2012-01-01

Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic question is if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthoversus retronasal response patterns. We found that at a physiologically relevant flow rate retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between ortho- and retronasal odor representations in the rat OB. PMID:22674270

Chemosensory event-related potentials in relation to side of stimulation, age, sex, and stimulus concentration.

PubMed

Stuck, B A; Frey, S; Freiburg, C; Hörmann, K; Zahnert, T; Hummel, T

2006-06-01

For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were recorded; stimuli were presented in different concentrations to the left and right nostril. Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor 'sex' for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to

Differences in peripheral sensory input to the olfactory bulb between male and female mice

NASA Astrophysics Data System (ADS)

Kass, Marley D.; Czarnecki, Lindsey A.; Moberly, Andrew H.; McGann, John P.

2017-04-01

Female mammals generally have a superior sense of smell than males, but the biological basis of this difference is unknown. Here, we demonstrate sexually dimorphic neural coding of odorants by olfactory sensory neurons (OSNs), primary sensory neurons that physically contact odor molecules in the nose and provide the initial sensory input to the brain’s olfactory bulb. We performed in vivo optical neurophysiology to visualize odorant-evoked OSN synaptic output into olfactory bub glomeruli in unmanipulated (gonad-intact) adult mice from both sexes, and found that in females odorant presentation evoked more rapid OSN signaling over a broader range of OSNs than in males. These spatiotemporal differences enhanced the contrast between the neural representations of chemically related odorants in females compared to males during stimulus presentation. Removing circulating sex hormones makes these signals slower and less discriminable in females, while in males they become faster and more discriminable, suggesting opposite roles for gonadal hormones in influencing male and female olfactory function. These results demonstrate that the famous sex difference in olfactory abilities likely originates in the primary sensory neurons, and suggest that hormonal modulation of the peripheral olfactory system could underlie differences in how males and females experience the olfactory world.

Deciphering the function of the CNGB1b subunit in olfactory CNG channels.

PubMed

Nache, Vasilica; Wongsamitkul, Nisa; Kusch, Jana; Zimmer, Thomas; Schwede, Frank; Benndorf, Klaus

2016-07-11

Olfactory cyclic nucleotide-gated (CNG) ion channels are key players in the signal transduction cascade of olfactory sensory neurons. The second messengers cAMP and cGMP directly activate these channels, generating a depolarizing receptor potential. Olfactory CNG channels are composed of two CNGA2 subunits and two modulatory subunits, CNGA4, and CNGB1b. So far the exact role of the modulatory subunits for channel activation is not fully understood. By measuring ligand binding and channel activation simultaneously, we show that in functional heterotetrameric channels not only the CNGA2 subunits and the CNGA4 subunit but also the CNGB1b subunit binds cyclic nucleotides and, moreover, also alone translates this signal to open the pore. In addition, we show that the CNGB1b subunit is the most sensitive subunit in a heterotetrameric channel to cyclic nucleotides and that it accelerates deactivation to a similar extent as does the CNGA4 subunit. In conclusion, the CNGB1b subunit participates in ligand-gated activation of olfactory CNG channels and, particularly, contributes to rapid termination of odorant signal in an olfactory sensory neuron.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels.

PubMed

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-03-01

1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

Octanol-solubility of dissolved and particulate trace metals in contaminated rivers: implications for metal reactivity and availability.

PubMed

Turner, Andrew; Mawji, Edward

2005-05-01

The lipid-like, amphiphilic solvent, n-octanol, has been used to determine a hydrophobic fraction of dissolved and particulate trace metals (Al, Cd, Co, Cu, Mn, Ni, Pb, Zn) in contaminated rivers. In a sample from the River Clyde, southwest Scotland, octanol-solubility was detected for all dissolved metals except Co, with conditional octanol-water partition coefficients, D(ow), ranging from about 0.2 (Al and Cu) to 1.25 (Pb). In a sample taken from the River Mersey, northwest England, octanol-solubility was detected for dissolved Al and Pb, but only after sample aliquots had been spiked with individual ionic metal standards and equilibrated. Spiking of the River Clyde sample revealed competition among different metals for hydrophobic ligands. Metal displacement from hydrophobic complexes was generally most significant following the addition of ionic Al or Pb, although the addition of either of these metals had little effect on the octanol-solubility of the other. In both river water samples hydrophobic metals were detected on the suspended particles retained by filtration following their extraction in n-octanol. In general, particulate Cu and Zn (up to 40%) were most available, and Al, Co and Pb most resistant (<1%) to octanol extraction. Distribution coefficients defining the concentration ratio of octanol-soluble particle-bound metal to octanol-soluble dissolved metal were in the range 10(3.3)-10(5.3)mlg(-1). The presence of hydrophobic dissolved and particulate metal species has implications for our understanding of the biogeochemical behaviour of metals in aquatic environments. Specifically, such species are predicted to exhibit characteristics of non-polar organic contaminants, including the potential to penetrate the lipid bilayer. Current strategies for assessing the bioavailability and toxicity of dissolved and particulate trace metals in natural waters may, therefore, require revision.

Fos Expression in the Olfactory Pathway of High- and Low-Sexually Performing Rams Exposed to Urine from Estrous or Ovariectomized Ewes

PubMed Central

Mirto, AJ; Austin, KJ; Uthlaut, VA; Roselli, CE; Alexander, BM

2015-01-01

Exposure to estrous ewe urine stimulates investigation and mounting activity in sexually active but not sexually inactive rams. It was hypothesized sexual indifference may result from an inability to detect olfactory cues or an interruption of the pathway from detection of the olfactory stimulus to the motor response. Sexually active (n=4) and inactive (n=3) rams were exposed to urine from estrous ewes. An additional group of sexually active rams (n=3) were exposed to urine from ovariectomized ewes. Rams were exsanguinated following 1 h of exposure to stimulus. Neural activity was determined in tissues of interest by the presence of fos and fos-related proteins detected by immunohistochemistry procedures. Sexually active rams exposed to urine from ovariectomized ewes had more (P ≤ 0.05) fos-positive cells in the olfactory bulb, but fewer (P = 0.03) fos-positive cells in the cortical amygdala compared to sexually active rams exposed to urine from estrous ewes. Sexually inactive rams had similar (P ≥ 0.13) numbers of fos positive neurons in the olfactory bulb and medial amygdala but fewer (P ≤ 0.04) in the central amygdala, bed nucleus of the stria terminalis and the medial preoptic area compared to sexually active rams exposed to urine from estrous ewes. Sexual inactivity was not associated with decreased hypothalamic function since fos activity was similar (P ≥ 0.14) among groups in the suprachiasmatic and ventral medial nucleus. Sexual inactivity is not likely due to an impaired ability to detect or process olfactory stimuli by the main olfactory bulb and medial-cortical amygdala. Sexually inactive rams may have reduced attentiveness to sexual stimuli and/or decreased responsiveness of regions in the brain which regulate reproductive behaviors. PMID:28348447

Response Times to Gustatory-Olfactory Flavor Mixtures: Role of Congruence.

PubMed

Shepard, Timothy G; Veldhuizen, Maria G; Marks, Lawrence E

2015-10-01

A mixture of perceptually congruent gustatory and olfactory flavorants (sucrose and citral) was previously shown to be detected faster than predicted by a model of probability summation that assumes stochastically independent processing of the individual gustatory and olfactory signals. This outcome suggests substantial integration of the signals. Does substantial integration also characterize responses to mixtures of incongruent flavorants? Here, we report simple response times (RTs) to detect brief pulses of 3 possible flavorants: monosodium glutamate, MSG (gustatory: "umami" quality), citral (olfactory: citrus quality), and a mixture of MSG and citral (gustatory-olfactory). Each stimulus (and, on a fraction of trials, water) was presented orally through a computer-operated, automated flow system, and subjects were instructed to press a button as soon as they detected any of the 3 non-water stimuli. Unlike responses previously found to the congruent mixture of sucrose and citral, responses here to the incongruent mixture of MSG and citral took significantly longer (RTs were greater) and showed lower detection rates than the values predicted by probability summation. This outcome suggests that the integration of gustatory and olfactory flavor signals is less extensive when the component flavors are perceptually incongruent rather than congruent, perhaps because incongruent flavors are less familiar. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cross-adaptation between Olfactory Responses Induced by Two Subgroups of Odorant Molecules

PubMed Central

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-01-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at −54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 ± 7 mV (mean ± SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants. PMID:12939391

Cross-adaptation between olfactory responses induced by two subgroups of odorant molecules.

PubMed

Takeuchi, Hiroko; Imanaka, Yukie; Hirono, Junzo; Kurahashi, Takashi

2003-09-01

It has long been believed that vertebrate olfactory signal transduction is mediated by independent multiple pathways (using cAMP and InsP3 as second messengers). However, the dual presence of parallel pathways in the olfactory receptor cell is still controversial, mainly because of the lack of information regarding the single-cell response induced by odorants that have been shown to produce InsP3 exclusively (but not cAMP) in the olfactory cilia. In this study, we recorded activities of transduction channels of single olfactory receptor cells to InsP3-producing odorants. When the membrane potential was held at -54 mV, application of InsP3-producing odorants to the ciliary region caused an inward current. The reversal potential was 0 +/- 7 mV (mean +/- SD, n = 10). Actually, InsP3-producing odorants generated responses in a smaller fraction of cells (lilial, 3.4%; lyral, 1.7%) than the cAMP-producing odorant (cineole, 26%). But, fundamental properties of responses were surprisingly homologous; namely, spatial distribution of the sensitivity, waveforms, I-V relation, and reversal potential, dose dependence, time integration of stimulus period, adaptation, and recovery. By applying both types of odorants alternatively to the same cell, furthermore, we observed cells to exhibit symmetrical cross-adaptation. It seems likely that even with odorants with different modalities adaptation occurs completely depending on the amount of current flow. The data will also provide evidence showing that olfactory response generation and adaptation are regulated by a uniform mechanism for a wide variety of odorants.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

PubMed Central

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant. The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques on three distinct cellular models: (1) CFTR-expressing Chinese hamster ovary cells, (2) human airway Calu-3 epithelial cells and (3) human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated 125I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. 125I efflux and Cl− currents induced by octanol were blocked by glibenclamide but insensitive to 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, as expected for a CFTR Cl− current. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF. PMID:14967738

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

PubMed

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.

Pressure reversal of the action of octanol on postsynaptic membranes from Torpedo.

PubMed Central

Braswell, L. M.; Miller, K. W.; Sauter, J. F.

1984-01-01

Octanol increases the binding of [3H]-acetylcholine to the desensitized state of the nicotinic receptor in postsynaptic membranes prepared from Torpedo californica. This increase in binding results from an increase in the affinity of [3H]-acetylcholine for its receptor without any change in the number of sites or the shape of the acetylcholine binding curve. High pressures of helium (300 atm) decrease [3H]-acetylcholine binding by a mechanism that changes only the affinity of acetylcholine binding. Helium pressure reverses the effect of octanol on the affinity of [3H]-acetylcholine for its receptor. This pressure reversal of the action of octanol at a postsynaptic membrane is consistent either with pressure counteracting an octanol-induced membrane expansion or with independent mechanisms for the actions of octanol and pressure. The data do not conform with a mechanism in which pressure displaces octanol from a binding site on the receptor protein. PMID:6487895

A pharmacological profile of the aldehyde receptor repertoire in rat olfactory epithelium

PubMed Central

Araneda, Ricardo C; Peterlin, Zita; Zhang, Xinmin; Chesler, Alex; Firestein, Stuart

2004-01-01

Several lines of evidence suggest that odorants are recognized through a combinatorial process in the olfactory system; a single odorant is recognized by multiple receptors and multiple odorants are recognized by the same receptor. However few details of how this might actually function for any particular odour set or receptor family are available. Approaching the problem from the ligands rather than the receptors, we used the response to a common odorant, octanal, as the basis for defining multiple receptor profiles. Octanal and other aldehydes induce large EOG responses in the rodent olfactory epithelium, suggesting that these compounds activate a large number of odour receptors (ORs). Here, we have determined and compared the pharmacological profile of different octanal receptors using Ca2+ imaging in isolated olfactory sensory neurones (OSNs). It is believed that each OSN expresses only one receptor, thus the response profile of each cell corresponds to the pharmacological profile of one particular receptor. We stimulated the cells with a panel of nine odorants, which included octanal, octanoic acid, octanol and cinnamaldehyde among others (all at 30μm). Cluster analysis revealed several distinct pharmacological profiles for cells that were all sensitive to octanal. Some receptors had a broad molecular range, while others were activated only by octanal. Comparison of the profiles with that of the one identified octanal receptor, OR-I7, indicated several differences. While OR-I7 is activated by low concentrations of octanal and blocked by citral, other receptors were less sensitive to octanal and not blocked by citral. A lower estimate for the maximal number of octanal receptors is between 33 and 55. This large number of receptors for octanal suggests that, although the peripheral olfactory system is endowed with high sensitivity, discrimination among different compounds probably requires further central processing. PMID:14724183

Olfactory lateralization in the chick.

PubMed

Vallortigara, G; Andrew, R J

1994-04-01

Chicks using their right nostril (and so with direct olfactory input to the right hemisphere), and presented simultaneously with two objects identical in visual appearance with the rearing object, and differing only in odour, chose that which smelled like the rearing object. Chicks using the left nostril chose equally readily but at random. Earlier work, using similar tests, has shown special interest of the right hemisphere in change in visual properties of familiar stimuli, suggesting that analysis of a wide range of properties of a familiar stimulus may be an important function of the right hemisphere in the chick, with consequent detection of novelty.

Antennal olfactory responses of adult meadow spittlebug, Philaenus spumarius, to volatile organic compounds (VOCs)

PubMed Central

Ganassi, Sonia; Pistillo, Marco O.; Di Domenico, Carmela; De Cristofaro, Antonio; Di Palma, Antonella Marta

2017-01-01

The meadow spittlebug, Philaenus spumarius L. (Hemiptera, Aphrophoridae) is a commonly found vector of Xylella fastidiosa Wells et al. (1987) strain subspecies pauca associated with the “Olive Quick Decline Syndrome” in Italy. To contribute to the knowledge of the adult P. spumarius chemoreceptivity, electroantennographic (EAG) responses of both sexes to 50 volatile organic compounds (VOCs) including aliphatic aldehydes, alcohols, esters, and ketones, terpenoids, and aromatics were recorded. Measurable EAG responses were elicited by all compounds tested. In both sexes, octanal, 2-octanol, 2-decanone, (E)-2-hexenyl acetate, and vanillin elicited the strongest antennal amplitude within the chemical groups of aliphatic saturated aldehydes, aliphatic alcohols, aliphatic acetates and aromatics, respectively. Male and female EAG responses to sulcatol, (±)linalool, and sulcatone were higher than those to other terpenoinds. In both sexes, the weakest antennal stimulants were phenethyl alcohol and 2-pentanone. Sexual differences in the EAG amplitude were found only for four of test compounds suggesting a general similarity between males and females in antennal sensitivity. The olfactory system of both sexes proved to be sensitive to changes in stimulus concentration, carbon chain length, and compound structure. Compounds with short carbon chain length (C5—C6) elicited lower EAG amplitudes than compounds with higher carbon chain length (C9—C10) in all classes of aliphatic hydrocarbons with different functional groups. The elucidation of the sensitivity profile of P. spumarius to a variety of VOCs provides a basis for future identification of behaviorally-active compounds useful for developing semiochemical-based control strategies of this pest. PMID:29287108

Dispersed three-pulse infrared photon echoes of nitrous oxide in water and octanol.

PubMed

Shattuck, J T; Schneck, J R; Chieffo, L R; Erramilli, S; Ziegler, L D

2013-12-12

Dispersed IR three-pulse photon echoes due to the antisymmetric (ν3) stretch mode of N2O dissolved in H2O and 1-octanol at room temperature are reported and analyzed. The experimentally determined transition frequency-frequency correlation function (FFCF) in these two solvents is explained in terms of inertial solvent contributions, hydrogen bond network fluctuations, and, for octanol, the motions of the alkyl chains. The H2O hydrogen bond fluctuations result in 1.5 ps FFCF decay, in agreement with relaxation rates determined from photon echo based measurements of other aqueous solutions including salt solutions. In octanol, hydrogen bond fluctuations decay on a slower time scale of 3.3 ps and alkyl chain motions result in an inhomogeneous broadening contribution to the ν3 absorption spectrum that decays on a 35 ps time scale. Rotational reorientation of N2O is nearly 3 times faster in octanol as compared to water. Although the vibrational ν3 N2O absorption line shapes in water and octanol are similar, the line widths result from different coherence loss mechanisms. A hot band contribution in the N2O in octanol solution is found to have a significant effect on the echo spectrum due to its correspondingly stronger transition moment than that of the fundamental transition. The dephasing dynamics of the N2O ν3 stretch mode is of interest as a probe in ultrafast studies of complex or nanoconfined systems with both hydrophobic and hydrophilic regions such as phospholipids, nucleic acids, and proteins. These results demonstrate the value of the N2O molecule to act as a reporter of equilibrium fluctuations in such complex systems particularly due to its solubility characteristics and long vibrational lifetime.

A Comparison of the Microbial Production and Combustion Characteristics of Three Alcohol Biofuels: Ethanol, 1-Butanol, and 1-Octanol.

PubMed

Kremer, Florian; Blank, Lars M; Jones, Patrik R; Akhtar, M Kalim

2015-01-01

Over the last decade, microbes have been engineered for the manufacture of a variety of biofuels. Saturated linear-chain alcohols have great potential as transport biofuels. Their hydrocarbon backbones, as well as oxygenated content, confer combustive properties that make it suitable for use in internal combustion engines. Herein, we compared the microbial production and combustion characteristics of ethanol, 1-butanol, and 1-octanol. In terms of productivity and efficiency, current microbial platforms favor the production of ethanol. From a combustion standpoint, the most suitable fuel for spark-ignition engines would be ethanol, while for compression-ignition engines it would be 1-octanol. However, any general conclusions drawn at this stage regarding the most superior biofuel would be premature, as there are still many areas that need to be addressed, such as large-scale purification and pipeline compatibility. So far, the difficulties in developing and optimizing microbial platforms for fuel production, particularly for newer fuel candidates, stem from our poor understanding of the myriad biological factors underpinning them. A great deal of attention therefore needs to be given to the fundamental mechanisms that govern biological processes. Additionally, research needs to be undertaken across a wide range of disciplines to overcome issues of sustainability and commercial viability.

A Comparison of the Microbial Production and Combustion Characteristics of Three Alcohol Biofuels: Ethanol, 1-Butanol, and 1-Octanol

PubMed Central

Kremer, Florian; Blank, Lars M.; Jones, Patrik R.; Akhtar, M. Kalim

2015-01-01

Over the last decade, microbes have been engineered for the manufacture of a variety of biofuels. Saturated linear-chain alcohols have great potential as transport biofuels. Their hydrocarbon backbones, as well as oxygenated content, confer combustive properties that make it suitable for use in internal combustion engines. Herein, we compared the microbial production and combustion characteristics of ethanol, 1-butanol, and 1-octanol. In terms of productivity and efficiency, current microbial platforms favor the production of ethanol. From a combustion standpoint, the most suitable fuel for spark-ignition engines would be ethanol, while for compression-ignition engines it would be 1-octanol. However, any general conclusions drawn at this stage regarding the most superior biofuel would be premature, as there are still many areas that need to be addressed, such as large-scale purification and pipeline compatibility. So far, the difficulties in developing and optimizing microbial platforms for fuel production, particularly for newer fuel candidates, stem from our poor understanding of the myriad biological factors underpinning them. A great deal of attention therefore needs to be given to the fundamental mechanisms that govern biological processes. Additionally, research needs to be undertaken across a wide range of disciplines to overcome issues of sustainability and commercial viability. PMID:26301219

Stimulus properties of inhaled substances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R.W.

1978-10-01

Inhaled substances can modify behavior by their toxic action, or because they are discriminable events, or because they can support or suppress behavior. They can be used as discriminative stimuli at concentrations above the olfactory threshold. Inhalants can elicit unconditioned reflexes. As aversive stimuli, they can be studied in respondent conditioning experiments (e.g. conditioned suppression), in punishment paradigms, or as negative reinforcers in escape paradigms. Inhalants can also be positive reinforcers; their intoxication properties have engendered patterns of chronic self-administration (solvent abuse). Such stimulus properties should be considered in industrial hygiene and environmental quality decisions. Laboratory techniques to study suchmore » properties abound.« less

Stimulus properties of inhaled substances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, R.W.

1978-01-01

Inhaled substances can modify behavior by their toxic action, or because they are discriminable events, or because they can support or suppress behavior. They can be used as discriminative stimuli at concentrations above the olfactory threshold. Inhalants can elicit unconditioned reflexes. As aversive stimuli, they can be studied in respondent conditioning experiments (e.g. conditioned suppression), in punishment paradigms, or as negative reinforcers in escape paradigms. Inhalants can also be positive reinforcers; their intoxicating properties have engendered patterns of chronic self-administration (solvent abuse). Such stimulus properties should be considered in industrial hygiene and environmental quality decisions. Laboratory techniques to study suchmore » properties abound.« less

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

PubMed

Chaillan, F A; Marchetti, E; Delfosse, F; Roman, F S; Soumireu-Mourat, B

1997-01-01

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Olfactory predator recognition in predator-naïve gray mouse lemurs (Microcebus murinus).

PubMed

Sündermann, Dina; Scheumann, Marina; Zimmermann, Elke

2008-05-01

Olfactory cues of predators, such as feces, are known to elicit antipredator responses in animals (e.g., avoidance, activity). To date, however, there is little information on olfactory predator recognition in primates. We tested whether the odor of feces of different predator categories (historical Malagasy predators and introduced predators) and of Malagasy nonpredators (control) induces antipredator behavior in captive born, predator-naïve gray mouse lemurs. In an olfactory predator experiment a mouse lemur was exposed to a particular odor, fixed at a preferred location, where the animal was trained to get a reward. The behavior of the mouse lemur toward the respective stimulus category was videotaped and quantified. Results showed that mouse lemurs avoided the place of odor presentation when the odor belonged to a predator. They reacted with a significantly enhanced activity when exposed to odors of carnivores compared to those of nonpredatory controls. These findings are in favor of a genetic predisposition of olfactory predator recognition that might be based on the perception of metabolites from meat digestion. PsycINFO Database Record (c) 2008 APA, all rights reserved.

An Evaluation of a Stimulus Preference Assessment of Auditory Stimuli for Adolescents with Developmental Disabilities

ERIC Educational Resources Information Center

Horrocks, Erin; Higbee, Thomas S.

2008-01-01

Previous researchers have used stimulus preference assessment (SPA) methods to identify salient reinforcers for individuals with developmental disabilities including tangible, leisure, edible and olfactory stimuli. In the present study, SPA procedures were used to identify potential auditory reinforcers and determine the reinforcement value of…

Interglomerular Connectivity within the Canonical and GC-D/Necklace Olfactory Subsystems

PubMed Central

Puche, Adam C.; Munger, Steven D.

2016-01-01

The mammalian main olfactory system contains several subsystems that differ not only in the receptors they express and the glomerular targets they innervate within the main olfactory bulb (MOB), but also in the strategies they use to process odor information. The canonical main olfactory system employs a combinatorial coding strategy that represents odorant identity as a pattern of glomerular activity. By contrast, the "GC-D/necklace" olfactory subsystem—formed by olfactory sensory neurons expressing the receptor guanylyl cyclase GC-D and their target necklace glomeruli (NGs) encircling the caudal MOB—is critical for the detection of a small number of semiochemicals that promote the acquisition of food preferences. The formation of these socially-transmitted food preferences requires the animal to integrate information about two types of olfactory stimuli: these specialized social chemosignals and the food odors themselves. However, the neural mechanisms with which the GC-D/necklace subsystem processes this information are unclear. We used stimulus-induced increases in intrinsic fluorescence signals to map functional circuitry associated with NGs and canonical glomeruli (CGs) in the MOB. As expected, CG-associated activity spread laterally through both the glomerular and external plexiform layers associated with activated glomeruli. Activation of CGs or NGs resulted in activity spread between the two types of glomeruli; there was no evidence of preferential connectivity between individual necklace glomeruli. These results support previous anatomical findings that suggest the canonical and GC-D/necklace subsystems are functionally connected and may integrate general odor and semiochemical information in the MOB. PMID:27902696

Sadness might isolate you in a non-smelling world: olfactory perception and depression

PubMed Central

Schablitzky, Sylvia; Pause, Bettina M.

2014-01-01

Major depressive disorder (MDD) occurs with a high prevalence among mental illnesses. MDD patients experience sadness and hopelessness, with blunted affective reactivity. However, such depressive episodes are also key symptoms in other depressive disorders, like Bipolar Disorder (BPD) or Seasonal Affective Disorder (SAD). Moreover, depressive symptoms can also be found in healthy individuals, but are experienced as less severe or for a shorter duration than in patients. Here, it is aimed to summarize studies investigating odor perception in depression, including depressive states in healthy individuals and patient populations. Odor perception in depression has been assessed with psychophysical methods (olfactory sensitivity, odor identification, and discrimination), and odor ratings (intensity, emotional valence, familiarity). In addition, some studies investigated affective reactions to odors, and physiological and anatomical correlates of odor perception in depression. The summary reveals that MDD is associated with reduced olfactory sensitivity. However, odor identification and discrimination scores seem to be unaffected by depression. The reduced olfactory sensitivity might be associated with a reduced ability to encode olfactory information and a reduced volume of the olfactory bulb. While similar processes seem to occur in healthy individuals experiencing depressive states, they have not been observed in BPD or SAD patients. However, in order to conclude that the reduced olfactory sensitivity is directly linked to depression, it is suggested that studies should implement control measures of cognitive performances or perceptual abilities in other stimulus modalities. It is concluded that the reduced olfactory performance in MDD patients seems to be disorder-, modality-, and test-specific, and that the application of an appropriate olfactory and cognitive test-battery might be highly useful in the differential diagnosis of MDD. PMID:24570666

Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

NASA Technical Reports Server (NTRS)

Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

1996-01-01

Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

Synchronized Activity in The Main and Accessory Olfactory Bulbs and Vomeronasal Amygdala Elicited by Chemical Signals in Freely Behaving Mice.

PubMed

Pardo-Bellver, Cecília; Martínez-Bellver, Sergio; Martínez-García, Fernando; Lanuza, Enrique; Teruel-Martí, Vicent

2017-08-30

Chemosensory processing in mammals involves the olfactory and vomeronasal systems, but how the activity of both circuits is integrated is unknown. In our study, we recorded the electrophysiological activity in the olfactory bulbs and the vomeronasal amygdala in freely behaving mice exploring a battery of neutral and conspecific stimuli. The exploration of stimuli, including a neutral stimulus, induced synchronic activity in the olfactory bulbs characterized by a dominant theta rhythmicity, with specific theta-gamma coupling, distinguishing between vomeronasal and olfactory structures. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in the nasal cavity and the vomeronasal pumping. In the amygdala, male stimuli are preferentially processed in the medial nucleus, whereas female cues induced a differential response in the posteromedial cortical amygdala. Thus, particular theta-gamma patterns in the olfactory network modulates the integration of chemosensory information in the amygdala, allowing the selection of an appropriate behaviour.

Cholinergic Modulation during Acquisition of Olfactory Fear Conditioning Alters Learning and Stimulus Generalization in Mice

ERIC Educational Resources Information Center

Pavesi, Eloisa; Gooch, Allison; Lee, Elizabeth; Fletcher, Max L.

2013-01-01

We investigated the role of cholinergic neurotransmission in olfactory fear learning. Mice receiving pairings of odor and foot shock displayed fear to the trained odor the following day. Pretraining injections of the nicotinic antagonist mecamylamine had no effect on subsequent freezing, while the muscarinic antagonist scopolamine significantly…

Zone fluidics for measurement of octanol-water partition coefficient of drugs.

PubMed

Wattanasin, Panwadee; Saetear, Phoonthawee; Wilairat, Prapin; Nacapricha, Duangjai; Teerasong, Saowapak

2015-02-20

A novel zone fluidics (ZF) system for the determination of the octanol-water partition coefficient (Pow) of drugs was developed. The ZF system consisted of a syringe pump with a selection valve, a holding column, a silica capillary flow-cell and an in-line spectrophotometer. Exact microliter volumes of solvents (octanol and phosphate buffer saline) and a solution of the drug, sandwiched between air segments, were sequentially loaded into the vertically aligned holding column. Distribution of the drug between the aqueous and octanol phases occurred by the oscillation movement of the syringe pump piston. Phase separation occurred due to the difference in densities. The liquid zones were then pushed into the detection flow cell. In this method, absorbance measurements in only one of the phase (octanol or aqueous) were employed, which together with the volumes of the solvents and pure drug sample, allowed the calculation of the Pow. The developed system was applied to the determination of the Pow of some common drugs. The log (Pow) values agreed well with a batch method (R(2)=0.999) and literature (R(2)=0.997). Standard deviations for intra- and inter-day analyses were both less than 0.1log unit. This ZF system provides a robust and automated method for screening of Pow values in the drug discovery process. Copyright © 2014 Elsevier B.V. All rights reserved.

Performance breakdown in optimal stimulus decoding.

PubMed

Lubomir Kostal; Lansky, Petr; Pilarski, Stevan

2015-06-01

One of the primary goals of neuroscience is to understand how neurons encode and process information about their environment. The problem is often approached indirectly by examining the degree to which the neuronal response reflects the stimulus feature of interest. In this context, the methods of signal estimation and detection theory provide the theoretical limits on the decoding accuracy with which the stimulus can be identified. The Cramér-Rao lower bound on the decoding precision is widely used, since it can be evaluated easily once the mathematical model of the stimulus-response relationship is determined. However, little is known about the behavior of different decoding schemes with respect to the bound if the neuronal population size is limited. We show that under broad conditions the optimal decoding displays a threshold-like shift in performance in dependence on the population size. The onset of the threshold determines a critical range where a small increment in size, signal-to-noise ratio or observation time yields a dramatic gain in the decoding precision. We demonstrate the existence of such threshold regions in early auditory and olfactory information coding. We discuss the origin of the threshold effect and its impact on the design of effective coding approaches in terms of relevant population size.

Calculating the Solubilities of Drugs and Drug-Like Compounds in Octanol.

PubMed

Alantary, Doaa; Yalkowsky, Samuel

2016-09-01

A modification of the Van't Hoff equation is used to predict the solubility of organic compounds in dry octanol. The new equation describes a linear relationship between the logarithm of the solubility of a solute in octanol to its melting temperature. More than 620 experimentally measured octanol solubilities, collected from the literature, are used to validate the equation without using any regression or fitting. The average absolute error of the prediction is 0.66 log units. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Olfactory abnormalities in Huntington's disease: decreased plasticity in the primary olfactory cortex of R6/1 transgenic mice and reduced olfactory discrimination in patients.

PubMed

Lazic, Stanley E; Goodman, Anna O G; Grote, Helen E; Blakemore, Colin; Morton, A Jennifer; Hannan, Anthony J; van Dellen, Anton; Barker, Roger A

2007-06-02

Reduced neuronal plasticity in the striatum, hippocampus, and neocortex is a common feature of transgenic mouse models of Huntington's disease (HD). Doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM) are associated with structural plasticity in the adult mammalian brain, are markers of newly formed neurons in the dentate gyrus of the adult hippocampus, and are highly expressed in primary olfactory (piriform) cortex. Animal studies have demonstrated that a reduction in plasticity in the piriform cortex is associated with a selective impairment in odour discrimination. Therefore, the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex were quantified as measures of plasticity in early stage (fifteen week old) R6/1 transgenic HD mice. The transgenic mice had a large reduction in the number of DCX and PSA-NCAM immunoreactive cells in the piriform cortex, similar to that previously reported in the R6/2 mice. We also tested whether odour discrimination, as well as identification and detection, were impaired in HD patients and found that patients (at a similar disease stage as the mice) had an impairment in odour discrimination and identification, but not odour detection. These results suggest that olfactory impairments observed in HD patients may be the result of reduced plasticity in the primary olfactory cortex.

Calmodulin as a downstream gene of octopamine-OAR α1 signalling mediates olfactory attraction in gregarious locusts.

PubMed

Xu, L; Li, L; Yang, P; Ma, Z

2017-02-01

The migratory locust (Locusta migratoria) shows aggregative traits in nymph marching bands and swarm formations through mutual olfactory attraction of conspecifics. However, olfactory preference in different nymph stages in gregarious locusts is not sufficiently explored. In this study, we found that the nymph olfactory preference for gregarious volatiles exhibited obvious variations at different developmental stages. The gregarious locusts show attractive response to conspecific volatiles from the third stadium. Transcriptome comparison between third- and fourth-stadium nymphs showed that the G protein-coupled receptor (GPCR) pathways are significantly enriched. Amongst the genes present in GPCR pathways, the expression level of calmodulin in locust brains significantly increased from the third- to the fourth-stadium nymphs. Amongst the four octopamine receptors (OARs) belonging to the GPCR family, only OAR α1 showed similar expression patterns to those of calmodulin, and knockdown of OAR α1 reduced the expression level of calmodulin. RNA interference of calmodulin decreased locomotion and induced the loss of olfactory attraction in gregarious locusts. Moreover, the activation of OAR α1 in calmodulin-knockdown locusts did not induce olfactory attraction of the nymphs to gregarious volatiles. Thus, calmodulin as a downstream gene of octopamine-OAR α1 (OA-OAR α1) signalling mediates olfactory attraction in gregarious locusts. Overall, this study provides novel insights into the mechanism of OA-OAR α1 signalling involved in olfactory attraction of gregarious locusts. © 2016 The Royal Entomological Society.

Guidepost neurons for the lateral olfactory tract: expression of metabotropic glutamate receptor 1 and innervation by glutamatergic olfactory bulb axons.

PubMed

Hirata, Tatsumi; Kumada, Tatsuro; Kawasaki, Takahiko; Furukawa, Tomonori; Aiba, Atsu; Conquet, François; Saga, Yumiko; Fukuda, Atsuo

2012-12-01

The guidepost neurons for the lateral olfactory tract, which are called lot cells, are the earliest-generated neurons in the neocortex. They migrate tangentially and ventrally further down this tract, and provide scaffolding for the olfactory bulb axons projecting into this pathway. The molecular profiles of the lot cells are largely uncharacterized. We found that lot cells specifically express metabotropic glutamate receptor subtype-1 at a very early stage of development. This receptor is functionally competent and responds to a metabotropic glutamate receptor agonist with a transient increase in the intracellular calcium ion concentration. When the glutamatergic olfactory bulb axons were electrically stimulated, lot cells responded to the stimulation with a calcium increase mainly via ionotropic glutamate receptors, suggesting potential neurotransmission between the axons and lot cells during early development. Together with the finding that lot cells themselves are glutamatergic excitatory neurons, our results provide another notable example of precocious interactions between the projecting axons and their intermediate targets. Copyright © 2012 Wiley Periodicals, Inc.

Evidence of conscious and subconscious olfactory information processing during word encoding: a magnetoencephalographic (MEG) study.

PubMed

Walla, Peter; Hufnagl, Bernd; Lehrner, Johann; Mayer, Dagmar; Lindinger, Gerald; Deecke, Lüder; Lang, Wilfried

2002-11-01

The present study was meant to distinguish between unconscious and conscious olfactory information processing and to investigate the influence of olfaction on word information processing. Magnetic field changes were recorded in healthy young participants during deep encoding of visually presented words whereby some of the words were randomly associated with an odor. All recorded data were then split into two groups. One group consisted of participants who did not consciously perceive the odor during the whole experiment whereas the other group did report continuous conscious odor perception. The magnetic field changes related to the condition 'words without odor' were subtracted from the magnetic field changes related to the condition 'words with odor' for both groups. First, an odor-induced effect occurred between about 200 and 500 ms after stimulus onset which was similar in both groups. It is interpreted to reflect an activity reduction during word encoding related to the additional olfactory stimulation. Second, a later effect occurred between about 600 and 900 ms after stimulus onset which differed between the two groups. This effect was due to higher brain activity related to the additional olfactory stimulation. It was more pronounced in the group consisting of participants who consciously perceived the odor during the whole experiment as compared to the other group. These results are interpreted as evidence that the later effect is related to conscious odor perception whereas the earlier effect reflects unconscious olfactory information processing. Furthermore, our study provides evidence that only the conscious perception of an odor which is simultaneously presented to the visual presentation of a word reduces its chance to be subsequently recognized.

Using measured octanol-air partition coefficients to explain environmental partitioning of organochlorine pesticides.

PubMed

Shoeib, Mahiba; Harner, Tom

2002-05-01

Octanol-air partition coefficients (Koa) were measured directly for 19 organochlorine (OC) pesticides over the temperature range of 5 to 35 degrees C. Values of log Koa at 25 degrees C ranged over three orders of magnitude, from 7.4 for hexachlorobenzene to 10.1 for 1,1-dichloro-2,2-bis(p-chlorophenyl) ethane. Measured values were compared to values calculated as KowRT/H (where R is the ideal gas constant [8.314 J mol(-1) K(-1)], T is absolute temperature, and H is Henry's law constant) were, in general, larger. Discrepancies of up to three orders of magnitude were observed, highlighting the need for direct measurements of Koa. Plots of Koa versus inverse absolute temperature exhibited a log-linear correlation. Enthalpies of phase transition between octanol and air (deltaHoa) were determined from the temperature slopes and were in the range of 56 to 105 kJ mol(-1) K(-1). Activity coefficients in octanol (gamma(o)) were determined from Koa and reported supercooled liquid vapor pressures (pL(o)), and these were in the range of 0.3 to 12, indicating near-ideal solution behavior. Differences in Koa values for structural isomers of hexachlorocyclohexane were also explored. A Koa-based model was described for predicting the partitioning of OC pesticides to aerosols and used to calculate particulate fractions at 25 and -10 degrees C. The model also agreed well with experimental results for several OC pesticides that were equilibrated with urban aerosols in the laboratory. A log-log regression of the particle-gas partition coefficient versus Koa had a slope near unity, indicating that octanol is a good surrogate for the aerosol organic matter.

Ascl1 (Mash1) Knockout Perturbs Differentiation of Nonneuronal Cells in Olfactory Epithelium

PubMed Central

Jang, Woochan; Wildner, Hendrik; Schwob, James E.

2012-01-01

The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium. PMID:23284756

[Conjugated variability of spontaneous activity and behavioral response to olfactory stimuli in the taiga tick (Ixodes persulcatus)].

PubMed

Romashchenko, A V; Shnaĭder, E P; Petrovskiĭ, D V; Moshkin, M P

2013-01-01

According to -the automatic tracing of the movement of ticks in a Petri dish, motivational variability of the spontaneous activity and behavioral response of the taiga tick to olfactory stimuli was analyzed. In the studied sample, two groups of ticks that differ in the movement trajectory in the absence of stimulus were isolated, including ticks that mainly moved on the edge of the dish at maximum accessible height (group 1) and ticks that mainly moved at the bottom and wall of the dish (group 2). It was registered that ticks of group 1 (as opposed to ticks of group 2) demonstrated a pronounced behavioral response to olfactory stimuli (human synthetic pheromones and ammonia) and negative geotaxis. It was established that belonging to these groups depended On the time of day when the testing was performed and did not depend on the physiological age and infectious status.

The Interglomerular Circuit Potently Inhibits Olfactory Bulb Output Neurons by Both Direct and Indirect Pathways.

PubMed

Liu, Shaolin; Puche, Adam C; Shipley, Michael T

2016-09-14

Sensory processing shapes our perception. In mammals, odor information is encoded by combinatorial activity patterns of olfactory bulb (OB) glomeruli. Glomeruli are richly interconnected by short axon cells (SACs), which form the interglomerular circuit (IGC). It is unclear how the IGC impacts OB output to downstream neural circuits. We combined in vitro and in vivo electrophysiology with optogenetics in mice and found the following: (1) the IGC potently and monosynaptically inhibits the OB output neurons mitral/tufted cells (MTCs) by GABA release from SACs: (2) gap junction-mediated electrical coupling is strong for the SAC→MTC synapse, but negligible for the SAC→ETC synapse; (3) brief IGC-mediated inhibition is temporally prolonged by the intrinsic properties of MTCs; and (4) sniff frequency IGC activation in vivo generates persistent MTC inhibition. These findings suggest that the temporal sequence of glomerular activation by sensory input determines which stimulus features are transmitted to downstream olfactory networks and those filtered by lateral inhibition. Odor identity is encoded by combinatorial patterns of activated glomeruli, the initial signal transformation site of the olfactory system. Lateral circuit processing among activated glomeruli modulates olfactory signal transformation before transmission to higher brain centers. Using a combination of in vitro and in vivo optogenetics, this work demonstrates that interglomerular circuitry produces potent inhibition of olfactory bulb output neurons via direct chemical and electrical synapses as well as by indirect pathways. The direct inhibitory synaptic input engages mitral cell intrinsic membrane properties to generate inhibition that outlasts the initial synaptic action. Copyright © 2016 the authors 0270-6474/16/369604-14$15.00/0.

The Interglomerular Circuit Potently Inhibits Olfactory Bulb Output Neurons by Both Direct and Indirect Pathways

PubMed Central

Puche, Adam C.; Shipley, Michael T.

2016-01-01

Sensory processing shapes our perception. In mammals, odor information is encoded by combinatorial activity patterns of olfactory bulb (OB) glomeruli. Glomeruli are richly interconnected by short axon cells (SACs), which form the interglomerular circuit (IGC). It is unclear how the IGC impacts OB output to downstream neural circuits. We combined in vitro and in vivo electrophysiology with optogenetics in mice and found the following: (1) the IGC potently and monosynaptically inhibits the OB output neurons mitral/tufted cells (MTCs) by GABA release from SACs: (2) gap junction-mediated electrical coupling is strong for the SAC→MTC synapse, but negligible for the SAC→ETC synapse; (3) brief IGC-mediated inhibition is temporally prolonged by the intrinsic properties of MTCs; and (4) sniff frequency IGC activation in vivo generates persistent MTC inhibition. These findings suggest that the temporal sequence of glomerular activation by sensory input determines which stimulus features are transmitted to downstream olfactory networks and those filtered by lateral inhibition. SIGNIFICANCE STATEMENT Odor identity is encoded by combinatorial patterns of activated glomeruli, the initial signal transformation site of the olfactory system. Lateral circuit processing among activated glomeruli modulates olfactory signal transformation before transmission to higher brain centers. Using a combination of in vitro and in vivo optogenetics, this work demonstrates that interglomerular circuitry produces potent inhibition of olfactory bulb output neurons via direct chemical and electrical synapses as well as by indirect pathways. The direct inhibitory synaptic input engages mitral cell intrinsic membrane properties to generate inhibition that outlasts the initial synaptic action. PMID:27629712

"Imposed" and "inherent" mucosal activity patterns. Their composite representation of olfactory stimuli

PubMed Central

1987-01-01

Both regional differences in mucosal sensitivity and a gas chromatography-like process along the mucosal sheet have been separately proposed in two sets of earlier studies to produce different odorant-dependent activity patterns across the olfactory mucosa. This investigation evaluated, in one study, whether and to what degree these two mechanisms contribute to the generation of these activity patterns. Summated multiunit discharges were simultaneously recorded from lateral (LN) and medial (MN) sites on the bullfrog's olfactory nerve to sample the mucosal activity occurring near the internal and external nares, respectively. Precisely controlled sniffs of four odorants (benzaldehyde, butanol, geraniol, and octane) were drawn through the frog's olfactory sac in both the forward (H1) and reverse (H2) hale directions. By combining the four resulting measurements, LNH1, LNH2, MNH1, and MNH2, in different mathematical expressions, indexes reflecting the relative effects of the chromatographic process, regional sensitivity, and hale direction could be calculated. Most importantly, the chromatographic process and the regional sensitivity differences both contributed significantly to the mucosal activity patterns. However, their relative roles varied markedly among the four odorants, ranging from complete dominance by either one to substantial contributions from each. In general, the more strongly an odorant was sorbed by the mucosa, the greater was the relative effect of the chromatographic process; the weaker the sorption, the greater the relative effect of regional sensitivity. Similarly, the greater an odorant's sorption, the greater was the effect of hale direction. Other stimulus variables (sniff volume, sniff duration, and the number of molecules within the sniff) had marked effects upon the overall size of the response. For strongly sorbed odorants, the effect of increasing volume was positive; for a weakly sorbed odorant, it was negative. The reverse may be true

Processing of odor mixtures in the zebrafish olfactory bulb.

PubMed

Tabor, Rico; Yaksi, Emre; Weislogel, Jan-Marek; Friedrich, Rainer W

2004-07-21

Components of odor mixtures often are not perceived individually, suggesting that neural representations of mixtures are not simple combinations of the representations of the components. We studied odor responses to binary mixtures of amino acids and food extracts at different processing stages in the olfactory bulb (OB) of zebrafish. Odor-evoked input to the OB was measured by imaging Ca2+ signals in afferents to olfactory glomeruli. Activity patterns evoked by mixtures were predictable within narrow limits from the component patterns, indicating that mixture interactions in the peripheral olfactory system are weak. OB output neurons, the mitral cells (MCs), were recorded extra- and intracellularly and responded to odors with stimulus-dependent temporal firing rate modulations. Responses to mixtures of amino acids often were dominated by one of the component responses. Responses to mixtures of food extracts, in contrast, were more distinct from both component responses. These results show that mixture interactions can result from processing in the OB. Moreover, our data indicate that mixture interactions in the OB become more pronounced with increasing overlap of input activity patterns evoked by the components. Emerging from these results are rules of mixture interactions that may explain behavioral data and provide a basis for understanding the processing of natural odor stimuli in the OB.

Smelling themselves: Dogs investigate their own odours longer when modified in an "olfactory mirror" test.

PubMed

Horowitz, Alexandra

2017-10-01

While domestic dogs, Canis familiaris, have been found to be skillful at social cognitive tasks and even some meta-cognitive tasks, they have not passed the test of mirror self-recognition (MSR). Acknowledging the motivational and sensory challenges that might hinder performance, even before the question of self-recognition is broached, this study creates and enacts a novel design extrapolated from the species' natural behaviour. Given dogs' use of olfactory signals in communication, this experiment presents dogs with various canisters for approach and investigation. Each holds an odorous stimulus: in the critical test, either an "olfactory mirror" of the subject - the dog's own urine - or one in which the odour stimulus is modified. By looking at subjects' investigation times of each canister, it is shown that dogs distinguish between the olfactory "image" of themselves when modified: investigating their own odour for longer when it had an additional odour accompanying it than when it did not. Such behaviour implies a recognition of the odour as being of or from "themselves." The ecological validity of this odour presentation is examined by presenting to the subjects odours of other known or unknown dogs: dogs spend longer investigating the odour of other dogs than their own odour. Finally, in a second experiment, subjects spent longer with the modified stimulus than with the modified odour by itself, indicating that novelty alone does not explain the dogs' behavior. This study translates the MSR study for a species whose primary sensory modality is olfaction, and finds both that natural sniffing behaviour can be replicated in the lab and that dogs show more investigative interest in their own odours when modified. Copyright © 2017 Elsevier B.V. All rights reserved.

Performance, combustion and emission analysis of mustard oil biodiesel and octanol blends in diesel engine

NASA Astrophysics Data System (ADS)

Devarajan, Yuvarajan; Munuswamy, Dinesh Babu; Nagappan, Beemkumar; Pandian, Amith Kishore

2018-01-01

Biodiesels from the mustard oil promise to be an alternative to the conventional diesel fuel due to their similarity in properties. Higher alcohols are added to neat Mustard oil biodiesel (M100) to vary the properties of biodiesel for improving its combustion, emission and performance characteristics. N-Octanol has the ability to act as an oxygen buffer during combustion which contributes to the catalytic effect and accelerates the combustion process. N-Octanol is dispersed to neat Mustard oil biodiesel in the form of emulsions at different dosage levels of 10, 20 and 30% by volume. Three emulsion fuels prepared for engine testing constitutes of 90% of biodiesel and 10% of n-Octanol (M90O10), 80% of biodiesel and 20% of n-Octanol (M80O20) and 70% of biodiesel and 30% of n-Octanol (M70O30) by volume respectively. AVL 5402 diesel engine is made to run on these fuels to study the effect of n-Octanol on combustion, emission and performance characteristics of the mustard oil biodiesel. Experimental results show that addition of n-octanol has a positive effect on performance, combustion and emission characteristics owing to its inbuilt oxygen content. N-octanol was found to be the better oxidizing catalyst as it was more effective in reducing HC and CO emissions. A significant reduction in NOx emission was found when fuelled with emulsion techniques. The blending of n-octanol to neat Mustard oil biodiesel reduces the energy and fuel consumption and a marginal increase in brake thermal efficiency. Further, n-octanol also reduces the ignition delay and aids the combustion.

Performance, combustion and emission analysis of mustard oil biodiesel and octanol blends in diesel engine

NASA Astrophysics Data System (ADS)

Devarajan, Yuvarajan; Munuswamy, Dinesh Babu; Nagappan, Beemkumar; Pandian, Amith Kishore

2018-06-01

Biodiesels from the mustard oil promise to be an alternative to the conventional diesel fuel due to their similarity in properties. Higher alcohols are added to neat Mustard oil biodiesel (M100) to vary the properties of biodiesel for improving its combustion, emission and performance characteristics. N-Octanol has the ability to act as an oxygen buffer during combustion which contributes to the catalytic effect and accelerates the combustion process. N-Octanol is dispersed to neat Mustard oil biodiesel in the form of emulsions at different dosage levels of 10, 20 and 30% by volume. Three emulsion fuels prepared for engine testing constitutes of 90% of biodiesel and 10% of n-Octanol (M90O10), 80% of biodiesel and 20% of n-Octanol (M80O20) and 70% of biodiesel and 30% of n-Octanol (M70O30) by volume respectively. AVL 5402 diesel engine is made to run on these fuels to study the effect of n-Octanol on combustion, emission and performance characteristics of the mustard oil biodiesel. Experimental results show that addition of n-octanol has a positive effect on performance, combustion and emission characteristics owing to its inbuilt oxygen content. N-octanol was found to be the better oxidizing catalyst as it was more effective in reducing HC and CO emissions. A significant reduction in NOx emission was found when fuelled with emulsion techniques. The blending of n-octanol to neat Mustard oil biodiesel reduces the energy and fuel consumption and a marginal increase in brake thermal efficiency. Further, n-octanol also reduces the ignition delay and aids the combustion.

Aging results in reduced epidermal growth factor receptor signaling, diminished olfactory neurogenesis, and deficits in fine olfactory discrimination.

PubMed

Enwere, Emeka; Shingo, Tetsuro; Gregg, Christopher; Fujikawa, Hirokazu; Ohta, Shigeki; Weiss, Samuel

2004-09-22

Previous studies demonstrating olfactory interneuron involvement in olfactory discrimination and decreased proliferation in the forebrain subventricular zone with age led us to ask whether olfactory neurogenesis and, consequently, olfactory discrimination were impaired in aged mice. Pulse labeling showed that aged mice (24 months of age) had fewer new interneurons in the olfactory bulb than did young adult (2 months of age) mice. However, the aged mice had more olfactory interneurons in total than their younger counterparts. Aged mice exhibited no differences from young adult mice in their ability to discriminate between two discrete odors but were significantly poorer at performing discriminations between similar odors (fine olfactory discrimination). Leukemia inhibitory factor receptor heterozygote mice, which have less neurogenesis and fewer olfactory interneurons than their wild-type counterparts, performed more poorly at fine olfactory discrimination than the wild types, suggesting that olfactory neurogenesis, rather than the total number of interneurons, was responsible for fine olfactory discrimination. Immunohistochemistry and Western blot analyses revealed a selective reduction in expression levels of epidermal growth factor (EGF) receptor (EGFR) signaling elements in the aged forebrain subventricular zone. Waved-1 mutant mice, which express reduced quantities of transforming growth factor-alpha, the predominant EGFR ligand in adulthood, phenocopy aged mice in olfactory neurogenesis and performance on fine olfactory discrimination tasks. These results suggest that the impairment in fine olfactory discrimination with age may result from a reduction in EGF-dependent olfactory neurogenesis.

Origins of correlated spiking in the mammalian olfactory bulb

PubMed Central

Gerkin, Richard C.; Tripathy, Shreejoy J.; Urban, Nathaniel N.

2013-01-01

Mitral/tufted (M/T) cells of the main olfactory bulb transmit odorant information to higher brain structures. The relative timing of action potentials across M/T cells has been proposed to encode this information and to be critical for the activation of downstream neurons. Using ensemble recordings from the mouse olfactory bulb in vivo, we measured how correlations between cells are shaped by stimulus (odor) identity, common respiratory drive, and other cells’ activity. The shared respiration cycle is the largest source of correlated firing, but even after accounting for all observable factors a residual positive noise correlation was observed. Noise correlation was maximal on a ∼100-ms timescale and was seen only in cells separated by <200 µm. This correlation is explained primarily by common activity in groups of nearby cells. Thus, M/T-cell correlation principally reflects respiratory modulation and sparse, local network connectivity, with odor identity accounting for a minor component. PMID:24082089

Odourant dominance in olfactory mixture processing: what makes a strong odourant?

PubMed Central

Schubert, Marco; Sandoz, Jean-Christophe; Galizia, Giovanni; Giurfa, Martin

2015-01-01

The question of how animals process stimulus mixtures remains controversial as opposing views propose that mixtures are processed analytically, as the sum of their elements, or holistically, as unique entities different from their elements. Overshadowing is a widespread phenomenon that can help decide between these alternatives. In overshadowing, an individual trained with a binary mixture learns one element better at the expense of the other. Although element salience (learning success) has been suggested as a main explanation for overshadowing, the mechanisms underlying this phenomenon remain unclear. We studied olfactory overshadowing in honeybees to uncover the mechanisms underlying olfactory-mixture processing. We provide, to our knowledge, the most comprehensive dataset on overshadowing to date based on 90 experimental groups involving more than 2700 bees trained either with six odourants or with their resulting 15 binary mixtures. We found that bees process olfactory mixtures analytically and that salience alone cannot predict overshadowing. After normalizing learning success, we found that an unexpected feature, the generalization profile of an odourant, was determinant for overshadowing. Odourants that induced less generalization enhanced their distinctiveness and became dominant in the mixture. Our study thus uncovers features that determine odourant dominance within olfactory mixtures and allows the referring of this phenomenon to differences in neural activity both at the receptor and the central level in the insect nervous system. PMID:25652840

Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in locusts.

PubMed

Guo, Xiaojiao; Ma, Zongyuan; Du, Baozhen; Li, Ting; Li, Wudi; Xu, Lingling; He, Jing; Kang, Le

2018-03-22

Dopamine receptor 1 (Dop1) mediates locust attraction behaviors, however, the mechanism by which Dop1 modulates this process remains unknown to date. Here, we identify differentially expressed small RNAs associated with locust olfactory attraction after activating and inhibiting Dop1. Small RNA transcriptome analysis and qPCR validation reveal that Dop1 activation and inhibition downregulates and upregulates microRNA-9a (miR-9a) expression, respectively. miR-9a knockdown in solitarious locusts increases their attraction to gregarious volatiles, whereas miR-9a overexpression in gregarious locusts reduces olfactory attraction. Moreover, miR-9a directly targets adenylyl cyclase 2 (ac2), causing its downregulation at the mRNA and protein levels. ac2 responds to Dop1 and mediates locust olfactory attraction. Mechanistically, Dop1 inhibits miR-9a expression through inducing the dissociation of La protein from pre-miR-9a and resulting in miR-9a maturation inhibition. Our results reveal a Dop1-miR-9a-AC2 circuit that modulates locust olfactory attraction underlying aggregation. This study suggests that miRNAs act as key messengers in the GPCR signaling.

Olfactory receptor neurons use gain control and complementary kinetics to encode intermittent odorant stimuli

PubMed Central

Gorur-Shandilya, Srinivas; Demir, Mahmut; Long, Junjiajia; Clark, Damon A; Emonet, Thierry

2017-01-01

Insects find food and mates by navigating odorant plumes that can be highly intermittent, with intensities and durations that vary rapidly over orders of magnitude. Much is known about olfactory responses to pulses and steps, but it remains unclear how olfactory receptor neurons (ORNs) detect the intensity and timing of natural stimuli, where the absence of scale in the signal makes detection a formidable olfactory task. By stimulating Drosophila ORNs in vivo with naturalistic and Gaussian stimuli, we show that ORNs adapt to stimulus mean and variance, and that adaptation and saturation contribute to naturalistic sensing. Mean-dependent gain control followed the Weber-Fechner relation and occurred primarily at odor transduction, while variance-dependent gain control occurred at both transduction and spiking. Transduction and spike generation possessed complementary kinetic properties, that together preserved the timing of odorant encounters in ORN spiking, regardless of intensity. Such scale-invariance could be critical during odor plume navigation. DOI: http://dx.doi.org/10.7554/eLife.27670.001 PMID:28653907

Refining the dual olfactory hypothesis: pheromone reward and odour experience.

PubMed

Martínez-García, Fernando; Martínez-Ricós, Joana; Agustín-Pavón, Carmen; Martínez-Hernández, Jose; Novejarque, Amparo; Lanuza, Enrique

2009-06-25

In rodents, sexual advertisement and gender recognition are mostly (if not exclusively) mediated by chemosignals. Specifically, there is ample evidence indicating that female mice are 'innately' attracted by male sexual pheromones that have critical non-volatile components and are detected by the vomeronasal organ. These pheromones can only get access to the vomeronasal organ by active pumping mechanisms that require close contact with the source of the stimulus (e.g. urine marks) during chemoinvestigation. We have hypothesised that male sexual pheromones are rewarding to female mice. Indeed, male-soiled bedding can be used as a reinforcer to induce conditioned place preference, provided contact with the bedding is allowed. The neural mechanisms of pheromone reward seem, however, different from those employed by other natural reinforcers, such as the sweetness or postingestive effects of sucrose. In contrast to vomeronasal-detected male sexual pheromones, male-derived olfactory stimuli (volatiles) are not intrinsically attractive to female mice. However, after repeated exposure to male-soiled bedding, intact female mice develop an acquired preference for male odours. On the contrary, in females whose accessory olfactory bulbs have been lesioned, exposure to male-soiled bedding induces aversion to male odorants. These considerations, together with data on the different properties of olfactory and vomeronasal receptors, lead us to make a proposal for the complementary roles that the olfactory and vomeronasal systems play in intersexual attraction and in other forms of intra- or inter-species communication.

Reduced nasal transport of insulin-like growth factor-1 to the mouse cerebrum with olfactory bulb resection.

PubMed

Shiga, Hideaki; Nagaoka, Mikiya; Washiyama, Kohshin; Yamamoto, Junpei; Yamada, Kentaro; Noda, Takuya; Harita, Masayuki; Amano, Ryohei; Miwa, Takaki

2014-09-01

Although the olfactory nerve is involved in nasal transport of insulin-like growth factor-1 (IGF-1) to the brain, to our knowledge there have been no direct assessments of the effects of olfactory nerve damage on this transport. To determine whether olfactory bulb resection resulted in reduced transport of nasally administered human recombinant IGF-1 (hIGF-1) to the cerebrum, we measured the uptake of nasally administered iodine-125 hIGF-1 ((125)I-hIGF-1) in the cerebrum as a percentage of that in the blood in male ICR mice subjected to left olfactory bulb resection (model mice) and in sham-operated male ICR mice (control mice). Phosphorylated extracellular signal-regulated kinase (ERK) 1/2 (Thr202/Tyr204)/(Thr185/Tyr187) as a percentage of total ERK 1/2 in the left cerebrum was also assessed by using enzyme-linked immunosorbent assay after nasal administration of hIGF-1. Uptake of nasally administered (125)I-hIGF-1 in the cerebrum as a percentage of that in the blood was significantly lower in the model group than in the control group 30min after nasal administration of hIGF-1. Unilateral olfactory bulb resection prevented nasally administered hIGF-1 from increasing the phosphorylation of ERK 1/2 in the mouse cerebrum in vivo. These findings suggest that olfactory bulb damage reduces nasal transport of hIGF-1 to the brain in vivo. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Olfactory Cleft Endoscopy Scale correlates with olfactory metrics in patients with chronic rhinosinusitis

PubMed Central

Soler, Zachary M.; Hyer, J. Madison; Karnezis, Tom T.; Schlosser, Rodney J.

2015-01-01

Introduction Olfactory loss affects a majority of patients with chronic rhinosinusitis (CRS). Traditional objective measures of disease severity, including endoscopy scales, focus upon the paranasal sinuses and often have weak correlation to olfaction. Methods Adults with CRS were prospectively evaluated by blinded reviewers with a novel Olfactory Cleft Endoscopy Scale (OCES) that evaluated discharge, polyps, edema, crusting and scarring of the olfactory cleft. Objective olfactory function was assessed using “Sniffin’ Sticks testing, including composite threshold-discrimination-identification (TDI) scores. Olfactory-specific quality-of-life was evaluated using the short modified version of the Questionnaire of Olfactory Disorders (QOD-NS). Inter- and intra-rater reliability was assessed among 3 reviewers for OCES grading. Multivariate linear regression was then used to test associations between OCES scores and measures of olfaction, controlling for potential confounding factors. Results The OCES score was evaluated in 38 patients and had a high overall reliability (ICC=0.92; 95% CI: 0.91–0.96). The OCES significantly correlated with objective olfaction as measured by TDI score (p<0.001), with TDI score falling by 1.13 points for every 1 point increase in OCES score. Similar significant associations were found for threshold, discrimination, and identification scores (p<0.003 for all) after controlling for age, gender, race, and reviewer/review. The OCES was also highly associated with patient-reported QOD-NS scores (p=0.009). Conclusion A novel olfactory cleft endoscopy scale shows high reliability and correlates with both objective and patient-reported olfaction in patients with CRS. Further studies to determine prognostic value and responsiveness to change are warranted. PMID:26718315

Gray Matter Volume Reduction of Olfactory Cortices in Patients With Idiopathic Olfactory Loss

PubMed Central

Yao, Linyin; Pinto, Jayant Marian; Yi, Xiaoli; Li, Li; Peng, Peng

2014-01-01

Idiopathic olfactory loss (IOL) is a common olfactory disorder. Little is known about the pathophysiology of this disease. Previous studies demonstrated decreased olfactory bulb (OB) volume in IOL patients when compared with controls. The aim of our study was to investigate structural brain alterations in areas beyond the OB. We acquired T1-weighted magnetic resonance images from 16 patients with IOL and from 16 age- and sex-matched controls on a 3T scanner. Voxel-based morphometry (VBM) was performed using VBM8 toolbox and SPM8 in a Matlab environment. Psychophysical testing confirmed that patients had higher scores for Toyota and Takagi olfactometer and lower scores for Sniffin’ Sticks olfactory test than controls (t = 46.9, P < 0.001 and t = 21.4, P < 0.001, respectively), consistent with olfactory dysfunction. There was a significant negative correlation between the 2 olfactory tests (r = −0.6, P = 0.01). In a volume of interest analysis including primary and secondary olfactory areas, we found patients with IOL to exhibit gray matter volume loss in the orbitofrontal cortex, anterior cingulate cortex, insular cortex, parahippocampal cortex, and the piriform cortex. The present study indicates that changes in the central brain structures proximal to the OB occur in IOL. Further investigations of this phenomenon may be helpful to elucidate the etiology of IOL. PMID:25240014

Olfactory deposition of inhaled nanoparticles in humans

PubMed Central

Garcia, Guilherme J. M.; Schroeter, Jeffry D.; Kimbell, Julia S.

2016-01-01

Context Inhaled nanoparticles can migrate to the brain via the olfactory bulb, as demonstrated in experiments in several animal species. This route of exposure may be the mechanism behind the correlation between air pollution and human neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Objectives This manuscript aims to (1) estimate the dose of inhaled nanoparticles that deposit in the human olfactory epithelium during nasal breathing at rest and (2) compare the olfactory dose in humans with our earlier dose estimates for rats. Materials and methods An anatomically-accurate model of the human nasal cavity was developed based on computed tomography scans. The deposition of 1–100 nm particles in the whole nasal cavity and its olfactory region were estimated via computational fluid dynamics (CFD) simulations. Our CFD methods were validated by comparing our numerical predictions for whole-nose deposition with experimental data and previous CFD studies in the literature. Results In humans, olfactory dose of inhaled nanoparticles is highest for 1–2 nm particles with approximately 1% of inhaled particles depositing in the olfactory region. As particle size grows to 100 nm, olfactory deposition decreases to 0.01% of inhaled particles. Discussion and conclusion Our results suggest that the percentage of inhaled particles that deposit in the olfactory region is lower in humans than in rats. However, olfactory dose per unit surface area is estimated to be higher in humans due to their larger minute volume. These dose estimates are important for risk assessment and dose-response studies investigating the neurotoxicity of inhaled nanoparticles. PMID:26194036

Opposite effects of the gap junction blocker octanol on focal cerebral ischemia occluded for different durations.

PubMed

Ding, Wenting; Zhou, Lequan; Liu, Wei; Guan, Li; Li, Xiaoying; Liu, Haimei; Yan, Fuman; Xu, Jinwen; Zeng, Weiyong; Qiu, Min

2014-06-01

Protectants and executioners have been demonstrated to be used by gap junctions in focal cerebral ischemia. Certain researchers hypothesized that the opposite role of gap junctions may be associated with the injury extent, which has been demonstrated to be highly correlated with occlusion duration. In order to examine this hypothesis directly, the effects of octanol, a frequently used drug, were examined to investigate the role of gap junctions, in rats following middle cerebral artery occlusion (MCAO) for 30 min/2 h and 24 h reperfusion, respectively. Octanol significantly reduced the infarct volume following 2 h of occlusion concomitant with lower neurological deficits, whereas it enlarged the infarct volume following 30 min of occlusion. Consistently, octanol attenuated the number of transferase dUTP nick-end labeling (TUNEL) positive neurons in the hippocampal CA1 region following 2 h of occlusion, while opposite effects were observed for 30 min of occlusion. Further immunohistochemical studies demonstrated that the expression of B-cell leukemia-2 (Bcl-2, anti-apoptotic protein) was upregulated and that Bcl-2-associated X (Bax, proapoptotic protein) was downregulated following 2 h of occlusion in the octanol group compared with the ischemic group. Conversely, octanol downregulated the expression of the Bcl-2 protein concomitant with increased Bax protein following 30 min of occlusion. These results indicated that the gap junction blocker octanol can protect against ischemic injury following long-term occlusion, however, can aggravate ischemic injury following short-term occlusion.

Performance breakdown in optimal stimulus decoding

NASA Astrophysics Data System (ADS)

Kostal, Lubomir; Lansky, Petr; Pilarski, Stevan

2015-06-01

Objective. One of the primary goals of neuroscience is to understand how neurons encode and process information about their environment. The problem is often approached indirectly by examining the degree to which the neuronal response reflects the stimulus feature of interest. Approach. In this context, the methods of signal estimation and detection theory provide the theoretical limits on the decoding accuracy with which the stimulus can be identified. The Cramér-Rao lower bound on the decoding precision is widely used, since it can be evaluated easily once the mathematical model of the stimulus-response relationship is determined. However, little is known about the behavior of different decoding schemes with respect to the bound if the neuronal population size is limited. Main results. We show that under broad conditions the optimal decoding displays a threshold-like shift in performance in dependence on the population size. The onset of the threshold determines a critical range where a small increment in size, signal-to-noise ratio or observation time yields a dramatic gain in the decoding precision. Significance. We demonstrate the existence of such threshold regions in early auditory and olfactory information coding. We discuss the origin of the threshold effect and its impact on the design of effective coding approaches in terms of relevant population size.

Olfactory cues from plants infected by powdery mildew guide foraging by a mycophagous ladybird beetle.

PubMed

Tabata, Jun; De Moraes, Consuelo M; Mescher, Mark C

2011-01-01

Powdery mildews (Erysiphales) are economically important plant pathogens that attack many agricultural crops. Conventional management strategies involving fungicide application face challenges, including the evolution of resistance and concerns over impacts on non-target organisms, that call for investigation of more sustainable alternatives. Mycophagous ladybird beetles (Coleoptera: Coccinellidae) feed on powdery mildew and have considerable potential as biological control agents; however, the foraging ecology and behavior of these beetles is not well understood. Here we document the olfactory cues presented by squash plants (Cucurbita moschata) infected by powdery mildew (Podosphaera sp.) and the behavioral responses of twenty-spotted ladybird beetles (Psyllobora vigintimaculata) to these cues. Volatile analyses through gas chromatography revealed a number of volatile compounds characteristic of infected plants, including 3-octanol and its analogues 1-octen-3-ol and 3-octanone. These compounds are typical "moldy" odorants previously reported in volatiles collected from other fungi. In addition, infected plants exhibited elevated emissions of several compounds also observed in collections from healthy leaves, including linalool and benzyl alcohol, which are reported to have anti-fungal properties. In Y-tube choice assays, P. vigintimaculata beetles displayed a significant preference for the odors of infected plants compared to those of healthy plants. Moreover, beetles exhibited strong attraction to one individual compound, 1-octen-3-ol, which was the most abundant of the characteristic fungal compounds identified. These results enhance our understanding of the olfactory cues that guide foraging by mycophagous insects and may facilitate the development of integrated disease-management strategies informed by an understanding of underlying ecological mechanisms.

Olfactory Cues from Plants Infected by Powdery Mildew Guide Foraging by a Mycophagous Ladybird Beetle

PubMed Central

Tabata, Jun; De Moraes, Consuelo M.; Mescher, Mark C.

2011-01-01

Powdery mildews (Erysiphales) are economically important plant pathogens that attack many agricultural crops. Conventional management strategies involving fungicide application face challenges, including the evolution of resistance and concerns over impacts on non-target organisms, that call for investigation of more sustainable alternatives. Mycophagous ladybird beetles (Coleoptera: Coccinellidae) feed on powdery mildew and have considerable potential as biological control agents; however, the foraging ecology and behavior of these beetles is not well understood. Here we document the olfactory cues presented by squash plants (Cucurbita moschata) infected by powdery mildew (Podosphaera sp.) and the behavioral responses of twenty-spotted ladybird beetles (Psyllobora vigintimaculata) to these cues. Volatile analyses through gas chromatography revealed a number of volatile compounds characteristic of infected plants, including 3-octanol and its analogues 1-octen-3-ol and 3-octanone. These compounds are typical “moldy” odorants previously reported in volatiles collected from other fungi. In addition, infected plants exhibited elevated emissions of several compounds also observed in collections from healthy leaves, including linalool and benzyl alcohol, which are reported to have anti-fungal properties. In Y-tube choice assays, P. vigintimaculata beetles displayed a significant preference for the odors of infected plants compared to those of healthy plants. Moreover, beetles exhibited strong attraction to one individual compound, 1-octen-3-ol, which was the most abundant of the characteristic fungal compounds identified. These results enhance our understanding of the olfactory cues that guide foraging by mycophagous insects and may facilitate the development of integrated disease-management strategies informed by an understanding of underlying ecological mechanisms. PMID:21876772

Multiplexing using synchrony in the zebrafish olfactory bulb.

PubMed

Friedrich, Rainer W; Habermann, Christopher J; Laurent, Gilles

2004-08-01

In the olfactory bulb (OB) of zebrafish and other species, odors evoke fast oscillatory population activity and specific firing rate patterns across mitral cells (MCs). This activity evolves over a few hundred milliseconds from the onset of the odor stimulus. Action potentials of odor-specific MC subsets phase-lock to the oscillation, defining small and distributed ensembles within the MC population output. We found that oscillatory field potentials in the zebrafish OB propagate across the OB in waves. Phase-locked MC action potentials, however, were synchronized without a time lag. Firing rate patterns across MCs analyzed with low temporal resolution were informative about odor identity. When the sensitivity for phase-locked spiking was increased, activity patterns became progressively more informative about odor category. Hence, information about complementary stimulus features is conveyed simultaneously by the same population of neurons and can be retrieved selectively by biologically plausible mechanisms, indicating that seemingly alternative coding strategies operating on different time scales may coexist.

Estimation of octanol/water partition coefficients using LSER parameters

USGS Publications Warehouse

Luehrs, Dean C.; Hickey, James P.; Godbole, Kalpana A.; Rogers, Tony N.

1998-01-01

The logarithms of octanol/water partition coefficients, logKow, were regressed against the linear solvation energy relationship (LSER) parameters for a training set of 981 diverse organic chemicals. The standard deviation for logKow was 0.49. The regression equation was then used to estimate logKow for a test of 146 chemicals which included pesticides and other diverse polyfunctional compounds. Thus the octanol/water partition coefficient may be estimated by LSER parameters without elaborate software but only moderate accuracy should be expected.

Odor-evoked inhibition of olfactory sensory neurons drives olfactory perception in Drosophila.

PubMed

Cao, Li-Hui; Yang, Dong; Wu, Wei; Zeng, Xiankun; Jing, Bi-Yang; Li, Meng-Tong; Qin, Shanshan; Tang, Chao; Tu, Yuhai; Luo, Dong-Gen

2017-11-07

Inhibitory response occurs throughout the nervous system, including the peripheral olfactory system. While odor-evoked excitation in peripheral olfactory cells is known to encode odor information, the molecular mechanism and functional roles of odor-evoked inhibition remain largely unknown. Here, we examined Drosophila olfactory sensory neurons and found that inhibitory odors triggered outward receptor currents by reducing the constitutive activities of odorant receptors, inhibiting the basal spike firing in olfactory sensory neurons. Remarkably, this odor-evoked inhibition of olfactory sensory neurons elicited by itself a full range of olfactory behaviors from attraction to avoidance, as did odor-evoked olfactory sensory neuron excitation. These results indicated that peripheral inhibition is comparable to excitation in encoding sensory signals rather than merely regulating excitation. Furthermore, we demonstrated that a bidirectional code with both odor-evoked inhibition and excitation in single olfactory sensory neurons increases the odor-coding capacity, providing a means of efficient sensory encoding.

Preparation and characterization of Ni based on natural zeolite catalyst for citronellol conversion to 3,7-Dimethyl-1-Octanol

NASA Astrophysics Data System (ADS)

Sudiyarmanto, Hidayati, Luthfiana N.; Kristiani, Anis; Ghaisani, Almira; Sukandar, Dede; Adilina, Indri B.; Tursiloadi, Silvester

2017-11-01

Citronella oil is a kind of essential oil that contains three main components, namely citronellal, citronellol, and geraniol. The high demand of citronellal and geraniol derivative prompted scientists to develop methods which are stereo-selective synthesis. A hydrogenation reaction using heterogeneous catalyst is one way of synthesis of citronella oil derivatives. In this research, synthesis of citronellol oil derivatives using Ni based on natural zeolite (Ni/ZAB) catalyst which is expected to produce the compound of 3,7-dimethyl-1-octanol. The catalyst was prepared by supporting Ni on natural zeolite by impregnation method. The physical and chemical properties of Ni/ZAB catalyst have been characterized by TGA, BET, XRD and FTIR instrumentations. Variation of pressure and temperature reactions were conducted to determine the optimum conditions for the hydrogenation of citronellol. The products from this reaction were analyzed using GC-MS instrumentation. The yield and selectivity of 3,7-dimethyl-1-octanol compound were achieved with optimum conditions at 200°C and 20 bar during 3 hours which produced around 51.97% and 47.81% respectively.

Prevalence of olfactory impairment in older adults.

PubMed

Murphy, Claire; Schubert, Carla R; Cruickshanks, Karen J; Klein, Barbara E K; Klein, Ronald; Nondahl, David M

2002-11-13

Older adults represent the fastest-growing segment of the US population, and prevalences of vision and hearing impairment have been extensively evaluated. However, despite the importance of sense of smell for nutrition and safety, the prevalence of olfactory impairment in older US adults has not been studied. To determine the prevalence of olfactory impairment in older adults. A total of 2491 Beaver Dam, Wis, residents aged 53 to 97 years participating in the 5-year follow-up examination (1998-2000) for the Epidemiology of Hearing Loss Study, a population-based, cross-sectional study. Olfactory impairment, assessed by the San Diego Odor Identification Test and self-report. The mean (SD) prevalence of impaired olfaction was 24.5% (1.7%). The prevalence increased with age; 62.5% (95% confidence interval [CI], 57.4%-67.7%) of 80- to 97-year-olds had olfactory impairment. Olfactory impairment was more prevalent among men (adjusted prevalence ratio, 1.92; 95% CI, 1.65-2.19). Current smoking, stroke, epilepsy, and nasal congestion or upper respiratory tract infection were also associated with increased prevalence of olfactory impairment. Self-reported olfactory impairment was low (9.5%) and this measure became less accurate with age. In the oldest group, aged 80 to 97 years, sensitivity of self-report was 12% for women and 18% for men. This study demonstrates that prevalence of olfactory impairment among older adults is high and increases with age. Self-report significantly underestimated prevalence rates obtained by olfaction testing. Physicians and caregivers should be particularly alert to the potential for olfactory impairment in the elderly population.

Freezing to the predator odor 2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is disrupted by olfactory bulb removal but not trigeminal deafferentation.

PubMed

Ayers, Luke W; Asok, Arun; Heyward, Frankie D; Rosen, Jeffrey B

2013-09-15

2,4,5 dihydro 2,5 trimethylthiazoline (TMT) is a synthesized component of red fox anal secretions that reliably elicits defensive behaviors in rats and mice. TMT differs from other predator odors because it is a single molecule, it can be synthesized in large quantities, and the dose for exposure is highly controllable in an experimental setting. TMT has become a popular tool for studying the brain mechanisms that mediate innate fear behavior to olfactory stimuli. However, this view of TMT as a biologically relevant olfactory stimulus has been challenged by suggestions that the odor elicits fear behavior due to its irritating properties, presumably working through a nociceptive mechanism. To address this criticism our lab measured freezing behavior in rats during exposures to 2 odors (TMT and butyric acid) and H2O (no odor control) following either surgical transection of the trigeminal nerves or ablation of the olfactory bulbs. Our findings (Experiment 1) indicate that freezing behavior to TMT requires an intact olfactory system, as indicated by the loss of freezing following olfactory bulb removal. Experiment 2 revealed that rats with trigeminal nerve transection freeze normally to TMT, suggesting the olfactory system mediates this behavior to TMT. A replication of Experiment 1 that included contextual fear conditioning revealed that the decreased freezing behavior was not due to an inability of olfactory bulb ablated rats to freeze (Experiment 3). Taken together, these findings support TMT's role as an ecologically relevant predator odor useful in experiments of unconditioned fear that is mediated via olfaction and not nociception. Copyright © 2013 Elsevier B.V. All rights reserved.

[Determination of equilibrium solubility and n-octanol/water partition coefficient of pulchinenosiden D by HPLC].

PubMed

Rao, Xiao-Yong; Yin, Shan; Zhang, Guo-Song; Luo, Xiao-Jian; Jian, Hui; Feng, Yu-Lin; Yang, Shi-Lin

2014-05-01

To determine the equilibrium solubility of pulchinenosiden D in different solvents and its n-octanol/water partition coefficients. Combining shaking flask method and high performance liquid chromatography (HPLC) to detect the n-octanol/water partition coefficients of pulchinenosiden D, the equilibrium solubility of pulchinenosiden D in six organic solvents and different pH buffer solution were determined by HPLC analysis. n-Octanol/water partition coefficients of pulchinenosiden D in different pH were greater than zero, the equilibrium solubility of pulchinenosiden D was increased with increase the pH of the buffer solution. The maximum equilibrium solubility of pulchinenosiden D was 255.89 g x L(-1) in methanol, and minimum equilibrium solubility of pulchinenosiden D was 0.20 g x L(-1) in acetonitrile. Under gastrointestinal physiological conditions, pulchinenosiden D exists in molecular state and it has good absorption but poor water-solubility, so increasing the dissolution rate of pulchinenosiden D may enhance its bioavailability.

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

PubMed

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.

Regeneration of synapses in the olfactory pathway of locusts after antennal deafferentation.

PubMed

Wasser, Hannah; Stern, Michael

2017-10-01

The olfactory pathway of the locust is capable of fast and precise regeneration on an anatomical level. Following deafferentation of the antenna either of young adult locusts, or of fifth instar nymphs, severed olfactory receptor neurons (ORNs) reinnervate the antennal lobe (AL) and arborize in AL microglomeruli. In the present study we tested whether these regenerated fibers establish functional synapses again. Intracellular recordings from AL projection neurons revealed that the first few odor stimulus evoked postsynaptic responses from regenerated ORNs from day 4-7 post crush on. On average, synaptic connections of regenerated afferents appeared faster in younger locusts operated as fifth instar nymphs than in adults. The proportions of response categories (excitatory vs. inhibitory) changed during regeneration, but were back to normal within 21 days. Odor-evoked oscillating extracellular local field potentials (LFP) were recorded in the mushroom body. These responses, absent after antennal nerve crush, reappeared, in a few animals as soon as 4 days post crush. Odor-induced oscillation patterns were restored within 7 days post crush. Both intra- and extracellular recordings indicate the capability of the locust olfactory system to re-establish synaptic contacts in the antennal lobe after antennal nerve lesion.

Flavor Identification and Intensity: Effects of Stimulus Context

PubMed Central

Hallowell, Emily S.; Parikh, Roshan; Veldhuizen, Maria G.

2016-01-01

Two experiments presented oral mixtures containing different proportions of the gustatory flavorant sucrose and an olfactory flavorant, either citral (Experiment 1) or lemon (Experiment 2). In 4 different sessions of each experiment, subjects identified each mixture as “mostly sugar” or “mostly citrus/lemon” or rated the perceived intensities of the sweet and citrus components. Different sessions also presented the mixtures in different contexts, with mixtures containing relatively high concentrations of sucrose or citral/lemon presented more often (skew sucrose or skew citral/lemon). As expected, in both experiments, varying stimulus context affected both identification and perceived intensity: Skewing to sucrose versus citral/lemon decreased the probability of identifying the stimuli as “mostly sugar” and reduced the ratings of sweet intensity relative to citrus intensity. Across both contextual conditions of both experiments, flavor identification associated closely with the ratio of the perceived sweet and citrus intensities. The results accord with a model, extrapolated from signal-detection theory, in which sensory events are represented as multisensory–multidimensional distributions in perceptual space. Changing stimulus context can shift the locations of the distributions relative to response criteria, Decision rules guide judgments based on both sensory events and criteria, these rules not necessarily being identical in tasks of identification and intensity rating. PMID:26830499

Odor preference and olfactory memory are impaired in Olfaxin-deficient mice.

PubMed

Islam, Saiful; Ueda, Masashi; Nishida, Emika; Wang, Miao-Xing; Osawa, Masatake; Lee, Dongsoo; Itoh, Masanori; Nakagawa, Kiyomi; Tana; Nakagawa, Toshiyuki

2018-06-01

Olfaxin, which is a BNIP2 and Cdc42GAP homology (BCH) domain-containing protein, is predominantly expressed in mitral and tufted (M/T) cells in the olfactory bulb (OB). Olfaxin and Caytaxin, which share 56.3% amino acid identity, are similar in their glutamatergic terminal localization, kidney-type glutaminase (KGA) interaction, and caspase-3 substrate. Although the deletion of Caytaxin protein causes human Cayman ataxia and ataxia in the mutant mouse, the function of Olfaxin is largely unknown. In this study, we generated Prune2 gene mutant mice (Prune2 Ex16-/- ; knock out [KO] mice) using the CRISPR/Cas9 system, during which the exon 16 containing start codon of Olfaxin mRNA was deleted. Exon 16 has 80 nucleotides and is contained in four of five Prune2 isoforms, including PRUNE2, BMCC1, BNIPXL, and Olfaxin/BMCC1s. The levels of Olfaxin mRNA and Olfaxin protein in the OB and piriform cortex of KO mice significantly decreased. Although Prune2 mRNA also significantly decreased in the spinal cord, the gross anatomy of the spinal cord and dorsal root ganglion (DRG) was intact. Further, disturbance of the sensory and motor system was not observed in KO mice. Therefore, in the current study, we examined the role of Olfaxin in the olfactory system where PRUNE2, BMCC1, and BNIPXL are scarcely expressed. Odor preference was impaired in KO mice using opposite-sex urinary scents as well as a non-social odor stimulus (almond). Results of the odor-aversion test demonstrated that odor-associative learning was disrupted in KO mice. Moreover, the NMDAR2A/NMDAR2B subunits switch in the piriform cortex was not observed in KO mice. These results indicated that Olfaxin may play a critical role in odor preference and olfactory memory. Copyright © 2018 Elsevier B.V. All rights reserved.

Crystal structure of [Eu(CyMe4-BTBP)2κ2O,O'-(NO3)](NO3)2·n-C8H17OH and its structure in 1-octanol solution.

PubMed

Lundberg, Daniel; Persson, Ingmar; Ekberg, Christian

2013-03-21

The structure of the [Eu(CyMe(4)-BTBP)(2)(NO(3))(n)]((3-n)+) complex in 1-octanol solution and solid state has been determined by EXAFS and X-ray crystallography. The crystal structure shows that 1-octanol binds only to the europium(III)-coordinated BTBP molecules through weak van der Waals forces, making it the first indication of the role of the extraction solvent.

Octanol/water partitioning simulation by RP-HPLC for structurally diverse acidic drugs: comparison of three columns in the presence and absence of n-octanol as the mobile phase additive.

PubMed

Giaginis, Costas; Theocharis, Stamatios; Tsantili-Kakoulidou, Anna

2013-12-01

The advantageous effect of n-octanol as a mobile phase additive for lipophilicity assessment of structurally diverse acidic drugs both in the neutral and ionized form was explored. Two RP C18 columns, ABZ+ and Aquasil, were used for the determination of logkw indices, and the results were compared with those previously reported on a base-deactivated silica column. At pH 2.5, the use of n-octanol-saturated buffer as the mobile phase aqueous component led to high-quality 1:1 correlation between logkw and logP for the ABZ+ column, while inferior statistics were obtained for Aquasil. At physiological pH, the correlations were significantly improved if strongly ionized acidic drugs were treated separately from weakly ionized ones. In the latter case, 1:1 correlations between logD7.4 and logkw(oct) indices were obtained in the presence of 0.25% n-octanol. Concerning strongly ionized compounds, adequate correlations were established under the same conditions; however, slopes were significantly lower than unity, while large negative intercepts were obtained. According to the absolute difference (diff = logD7.4 – logkw) pattern, base-deactivated silica showed a better performance than ABZ+, however, the latter seems more efficient for the lipophilicity assessment of highly lipophilic acidic compounds. Aquasil may be the column of choice if logD7.4<3 with the limitation, however, that very hydrophilic compounds cannot be measured.

The Olfactory Mosaic: Bringing an Olfactory Network Together for Odor Perception.

PubMed

Courtiol, Emmanuelle; Wilson, Donald A

2017-01-01

Olfactory perception and its underlying neural mechanisms are not fixed, but rather vary over time, dependent on various parameters such as state, task, or learning experience. In olfaction, one of the primary sensory areas beyond the olfactory bulb is the piriform cortex. Due to an increasing number of functions attributed to the piriform cortex, it has been argued to be an associative cortex rather than a simple primary sensory cortex. In fact, the piriform cortex plays a key role in creating olfactory percepts, helping to form configural odor objects from the molecular features extracted in the nose. Moreover, its dynamic interactions with other olfactory and nonolfactory areas are also critical in shaping the olfactory percept and resulting behavioral responses. In this brief review, we will describe the key role of the piriform cortex in the larger olfactory perceptual network, some of the many actors of this network, and the importance of the dynamic interactions among the piriform-trans-thalamic and limbic pathways.

Estimating the physicochemical properties of polyhalogenated aromatic and aliphatic compounds using UPPER: part 2. Aqueous solubility, octanol solubility and octanol-water partition coefficient.

PubMed

Admire, Brittany; Lian, Bo; Yalkowsky, Samuel H

2015-01-01

The UPPER (Unified Physicochemical Property Estimation Relationships) model uses additive and non-additive parameters to estimate 20 biologically relevant properties of organic compounds. The model has been validated by Lian and Yalkowsky (2014) on a data set of 700 hydrocarbons. Recently, Admire et al. (2014) expanded the model to predict the boiling and melting points of 1288 polyhalogenated benzenes, biphenyls, dibenzo-p-dioxins, diphenyl ethers, anisoles and alkanes. In this work, 19 new group descriptors are determined and used to predict the aqueous solubilities, octanol solubilities and the octanol-water coefficients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Similar increases in extracellular lactic acid in the limbic system during epileptic and/or olfactory stimulation.

PubMed

Fornai, F; Bassi, L; Gesi, M; Giorgi, F S; Guerrini, R; Bonaccorsi, I; Alessandrì, M G

2000-01-01

and there was no further increase in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulation occurred with site specificity in the rhinencephalon (hippocampus, piriform and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natural stimuli (i.e. tail pinch) produced a similar increase in extracellular lactate in all brain areas under investigation. The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induced by the systemic convulsant pylocarpine (maximum: 2.286+/-0.195 mM and 1.803+/-0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely from local anoxia or other pathological changes.

Brain activation associated to olfactory conditioned same-sex partner preference in male rats.

PubMed

Coria-Avila, Genaro A; Cibrian-Llanderal, Tamara; Díaz-Estrada, Victor X; García, Luis I; Toledo-Cárdenas, Rebeca; Pfaus, James G; Manzo, Jorge

2018-03-01

Sexual preferences can be strongly modified by Pavlovian learning. For instance, olfactory conditioned same-sex partner preference can occur when a sexually naïve male cohabits with an scented male during repeated periods under the effects of enhanced D2-type activity. Preference is observed days later via social and sexual behaviors. Herein we explored brain activity related to learned same-sex preference (Fos-Immunoreactivity, IR) following exposure to a conditioned odor paired with same-sex preference. During conditioning trials males received either saline or the D2-type receptor agonist quinpirole (QNP) and cohabitated during 24 h with a stimulus male that bore almond scent on the back as conditioned stimulus. This was repeated every 4 days, for a total of three trials. In a drug-free final test we assessed socio/sexual partner preference between the scented male and a receptive female. The results indicated that QNP-conditioned males developed a same-sex preference observed via contact, time spent, olfactory investigations, and non-contact erections. By contrast, saline-conditioned and intact (non-exposed to conditioning) males expressed an unconditioned preference for the female. Four days later the males were exposed to almond scent and their brains were processed for Fos-IR. Results indicated that the QNP-conditioned group expressed more Fos-IR in the nucleus accumbens (AcbSh), medial preoptic area (MPA), piriform cortex (Pir) and ventromedial nucleus of the hypothalamus (VMH) as compared to saline-conditioned. Intact males expressed the lowest Fos-IR in AcbSh and VMH, but the highest in MPA and Pir. We discuss the role of these areas in the learning process of same-sex partner preferences and olfactory discrimination. Copyright © 2018 Elsevier Inc. All rights reserved.

Rapid determination of octanol-water partition coefficient using vortex-assisted liquid-liquid microextraction.

PubMed

Román, Iván P; Mastromichali, Anna; Tyrovola, Konstantina; Canals, Antonio; Psillakis, Elefteria

2014-02-21

Vortex-assisted liquid-liquid microextraction (VALLME) coupled with high-performance liquid chromatography (HPLC) is proposed here for the rapid determination of octanol-water partitioning coefficients (Kow). VALLME uses vortex agitation, a mild emulsification procedure, to disperse microvolumes of octanol in the aqueous phase thus increasing the interfacial contact area and ensuring faster partitioning rates. With VALLME, 2min were enough to achieve equilibrium conditions between the octanolic and aqueous phases. Upon equilibration, separation was achieved using centrifugation and the octanolic microdrop was collected and analyzed in a HPLC system. Six model compounds with logKow values ranging between ∼0.5 and 3.5 were used during the present investigations. The proposed method produced logKow values that were consistent with previously published values and the recorded uncertainty was well within the acceptable log unit range. Overall, the key features of the proposed Kow determination procedure comprised speed, reliability, simplicity, low cost and minimal solvent consumption. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of Methylenebicyclo[3.2.1]octanol by a Sm(II)-Induced 1,2-Rearrangement Reaction with Ring Expansion of Methylenebicyclo[4.2.0]octanone.

PubMed

Takatori, Kazuhiko; Ota, Shoya; Tendo, Kenta; Matsunaga, Kazuma; Nagasawa, Kokoro; Watanabe, Shinya; Kishida, Atsushi; Kogen, Hiroshi; Nagaoka, Hiroto

2017-07-21

Direct conversion of methylenebicyclo[4.2.0]octanone to methylenebicyclo[3.2.1]octanol by a Sm(II)-induced 1,2-rearrangement with ring expansion of the methylenecyclobutane is described. Three conditions were optimized to allow the adaptation of this approach to various substrates. A rearrangement mechanism is proposed involving the generation of a ketyl radical and cyclopentanation by ketyl-olefin cyclization, followed by radical fragmentation and subsequent protonation.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers.

PubMed

Laska, M; Shepherd, G M

2007-01-05

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species' olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships.

Olfactory discrimination ability of CD-1 mice for a large array of enantiomers

PubMed Central

Laska, Matthias; Shepherd, Gordon M.

2006-01-01

With use of a conditioning paradigm, the ability of eight CD-1 mice to distinguish between 15 enantiomeric odor pairs was investigated. The results demonstrate a) that CD-1 mice are capable of discriminating between all odor pairs tested, b) that the enantiomeric odor pairs clearly differed in their degree of discriminability and thus in their perceptual similarity, and c) that pre-training with the rewarded stimuli led to improved initial but not terminal or overall performance. A comparison between the proportion of discriminated enantiomeric odor pairs of the CD-1 mice and those of other species tested in earlier studies on the same discrimination tasks (or on subsets thereof) shows a significant positive correlation between discrimination performance and the number of functional olfactory receptor genes. These findings provide the first evidence of a highly developed ability of CD-1 mice to discriminate between an array of non-pheromonal chiral odorants. Further, they suggest that a species′ olfactory discrimination capabilities for these odorants may be correlated with its number of functional olfactory receptor genes. The data presented here may provide useful information for the interpretation of findings from electrophysiological or imaging studies in the mouse and the elucidation of odor structure-activity relationships. PMID:17045753

PI3K-dependent antagonism in mammalian olfactory receptor neurons

PubMed Central

Ukhanov, Kirill; Brunert, Daniela; Corey, Elizabeth; Ache, Barry W.

2011-01-01

Phosphoinositide (PI) signaling, in particular PI3Kinase (PI3K) signaling, has been implicated in mediating inhibitory odorant input to mammalian olfactory receptor neurons (ORNs). To better understand this phenomenon we investigated PI3K-dependent inhibition between single odorant pairs. The concentration-dependent inhibition of the response of native rat ORNs to octanol by citral is PI3K-dependent; blocking PI3K activity with the β and γ isoform-specific inhibitors AS252424 and TGX221 eliminated or strongly reduced the inhibition. Interestingly, blocking PI3K also changed the apparent agonist strength of the otherwise non-competitive antagonist citral. The excitation evoked by citral after blocking PI3K, could be suppressed by the adenylate cyclase III (ACIII) blockers MDL12330A and SQ22536, indicating that citral could also activate ACIII, presumably through the canonical OR. The G protein Gβγ subunit blockers suramin, gallein and M119 suppressed citral’s inhibition of the response to octanol, indicating that the activation of PI3K by citral was G protein dependent, consistent with the idea that inhibition acts through the canonical OR. Lilial similarly antagonized the response to isoamyl acetate in other ORNs, indicating the effect generalizes to at least one other odorant pair. The ability of methyl-isoeugenol, limonene, α-pinene, isovaleric acid and isosafrole to inhibit the response of other ORNs to IBMX/forskolin in a PI3K-dependent manner argues the effect generalizes to yet other structurally dissimilar odorants. Our findings collectively raise the interesting possibility that the OR serves as a molecular logic gate when mammalian ORNs are activated by natural, complex mixtures containing both excitatory and inhibitory odorants. PMID:21209212

IGF1-Dependent Synaptic Plasticity of Mitral Cells in Olfactory Memory during Social Learning.

PubMed

Liu, Zhihui; Chen, Zijun; Shang, Congping; Yan, Fei; Shi, Yingchao; Zhang, Jiajing; Qu, Baole; Han, Hailin; Wang, Yanying; Li, Dapeng; Südhof, Thomas C; Cao, Peng

2017-07-05

During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. Copyright © 2017 Elsevier Inc. All rights reserved.

EOL-1, the Homolog of the Mammalian Dom3Z, Regulates Olfactory Learning in C. elegans

PubMed Central

Shen, Yu; Zhang, Jiangwen; Calarco, John A.

2014-01-01

Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. PMID:25274815

Initiation of olfactory placode development and neurogenesis is blocked in mice lacking both Six1 and Six4.

PubMed

Chen, Binglai; Kim, Eun-Hee; Xu, Pin-Xian

2009-02-01

Mouse olfactory epithelium (OE) originates from ectodermally derived placode, the olfactory placode that arises at the anterior end of the neural plate. Tissue grafting and recombination experiments suggest that the placode is derived from a common preplacodal domain around the neural plate and its development is directed by signals arising from the underlying mesoderm and adjacent neuroectoderm. In mice, loss of Six1 affects OE morphogenesis but not placode formation. We show here that embryos lacking both Six1 and Six4 failed to form the olfactory placode but the preplacodal region appeared to be specified as judged by the expression of Eya2, which marks the common preplacodal domain, suggesting a synergistic requirement of Six1 and Six4 in patterning the preplacodal ectoderm to a morphologic placode. Our results show that Six1 and Six4 are coexpressed in the preplacodal ectoderm from E8.0. In the olfactory pit, Six4 expression was observed in the peripheral precursors that overlap with Mash1-expressing cells, the early committed neuronal lineage. In contrast, Six1 is highly distributed in the peripheral regions where stem cells reside at E10.5 and it overlaps with Sox2 expression. Both genes are expressed in the basal and apical neuronal progenitors in the OE. Analyses of Six1;Six4 double mutant embryos demonstrated that the slightly thickened epithelium observed in the mutant was not induced for neuronal development. In contrast, in Six1(-/-) embryos, all neuronal lineage markers were initially expressed but the pattern of their expression was altered. Although very few, the pioneer neurons were initially present in the Six1 mutant OE. However, neurogenesis ceased by E12.5 due to markedly increased cell apoptosis and reduced proliferation, thus defining the cellular defects occurring in Six1(-/-) OE that have not been previously observed. Our findings demonstrate that Six1/4 function at the top of early events controlling olfactory placode formation and

Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

PubMed

Shen, Hung-Chang; Chu, Sao-Yu; Hsu, Tsai-Chi; Wang, Chun-Han; Lin, I-Ya; Yu, Hung-Hsiang

2017-04-01

Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

Stimulus-to-matching-stimulus interval influences N1, P2, and P3b in an equiprobable Go/NoGo task.

PubMed

Steiner, Genevieve Z; Barry, Robert J; Gonsalvez, Craig J

2014-10-01

Previous research has shown that as the stimulus-to-matching-stimulus interval (including the target-to-target interval, TTI, and nontarget-to-nontarget interval, NNI) increases, the amplitude of the P300 ERP component increases systematically. Here, we extended previous P300 research and explored TTI and NNI effects on the various ERP components elicited in an auditory equiprobable Go/NoGo task. We also examined whether a similar mechanism was underpinning interval effects in early ERP components (e.g., N1). Thirty participants completed a specially-designed variable-ISI equiprobable task whilst their EEG activity was recorded. Component amplitudes were extracted using temporal PCA with unrestricted Varimax rotation. As expected, N1, P2, and P3b amplitudes increased as TTI and NNI increased, however, Processing Negativity (PN) and Slow Wave (SW) did not show the same systematic change with interval increments. To determine the origin of interval effects in sequential processing, a multiple regression analysis was conducted on each ERP component including stimulus type, interval, and all preceding components as predictors. These analyses showed that matching-stimulus interval predicted N1, P3b, and weakly predicted P2, but not PN or SW; SW was determined by P3b only. These results suggest that N1, P3b, and to some extent, P2, are affected by a similar temporal mechanism. However, the dissimilar pattern of results obtained for sequential ERP components indicates that matching-stimulus intervals are not affecting all aspects of stimulus processing. This argues against a global mechanism, such as a pathway-specific refractory effect, and suggests that stimulus processing is occurring in parallel pathways, some of which are not affected by temporal manipulations of matching-stimulus interval. Copyright © 2014 Elsevier B.V. All rights reserved.

The value of identity: olfactory notes on orbitofrontal cortex function.

PubMed

Gottfried, Jay A; Zelano, Christina

2011-12-01

Neuroscientific research has emphatically promoted the idea that the key function of the orbitofrontal cortex (OFC) is to encode value. Associative learning studies indicate that OFC representations of stimulus cues reflect the predictive value of expected outcomes. Neuroeconomic studies suggest that the OFC distills abstract representations of value from discrete commodities to optimize choice. Although value-based models provide good explanatory power for many different findings, these models are typically disconnected from the very stimuli and commodities giving rise to those value representations. Little provision is made, either theoretically or empirically, for the necessary cooperative role of object identity, without which value becomes orphaned from its source. As a step toward remediating the value of identity, this review provides a focused olfactory survey of OFC research, including new work from our lab, to highlight the elemental involvement of this region in stimulus-specific predictive coding of both perceptual outcomes and expected values. © 2011 New York Academy of Sciences.

Complementary codes for odor identity and intensity in olfactory cortex

PubMed Central

Bolding, Kevin A; Franks, Kevin M

2017-01-01

The ability to represent both stimulus identity and intensity is fundamental for perception. Using large-scale population recordings in awake mice, we find distinct coding strategies facilitate non-interfering representations of odor identity and intensity in piriform cortex. Simply knowing which neurons were activated is sufficient to accurately represent odor identity, with no additional information about identity provided by spike time or spike count. Decoding analyses indicate that cortical odor representations are not sparse. Odorant concentration had no systematic effect on spike counts, indicating that rate cannot encode intensity. Instead, odor intensity can be encoded by temporal features of the population response. We found a subpopulation of rapid, largely concentration-invariant responses was followed by another population of responses whose latencies systematically decreased at higher concentrations. Cortical inhibition transforms olfactory bulb output to sharpen these dynamics. Our data therefore reveal complementary coding strategies that can selectively represent distinct features of a stimulus. DOI: http://dx.doi.org/10.7554/eLife.22630.001 PMID:28379135

Dnmts and Tet target memory-associated genes after appetitive olfactory training in honey bees

PubMed Central

Biergans, Stephanie D.; Giovanni Galizia, C.; Reinhard, Judith; Claudianos, Charles

2015-01-01

DNA methylation and demethylation are epigenetic mechanisms involved in memory formation. In honey bees DNA methyltransferase (Dnmt) function is necessary for long-term memory to be stimulus specific (i.e. to reduce generalization). So far, however, it remains elusive which genes are targeted and what the time-course of DNA methylation is during memory formation. Here, we analyse how DNA methylation affects memory retention, gene expression, and differential methylation in stimulus-specific olfactory long-term memory formation. Out of 30 memory-associated genes investigated here, 9 were upregulated following Dnmt inhibition in trained bees. These included Dnmt3 suggesting a negative feedback loop for DNA methylation. Within these genes also the DNA methylation pattern changed during the first 24 hours after training. Interestingly, this was accompanied by sequential activation of the DNA methylation machinery (i.e. Dnmts and Tet). In sum, memory formation involves a temporally complex epigenetic regulation of memory-associated genes that facilitates stimulus specific long-term memory in the honey bee. PMID:26531238

Parallel representation of stimulus identity and intensity in a dual pathway model inspired by the olfactory system of the honeybee.

PubMed

Schmuker, Michael; Yamagata, Nobuhiro; Nawrot, Martin Paul; Menzel, Randolf

2011-01-01

The honeybee Apis mellifera has a remarkable ability to detect and locate food sources during foraging, and to associate odor cues with food rewards. In the honeybee's olfactory system, sensory input is first processed in the antennal lobe (AL) network. Uniglomerular projection neurons (PNs) convey the sensory code from the AL to higher brain regions via two parallel but anatomically distinct pathways, the lateral and the medial antenno-cerebral tract (l- and m-ACT). Neurons innervating either tract show characteristic differences in odor selectivity, concentration dependence, and representation of mixtures. It is still unknown how this differential stimulus representation is achieved within the AL network. In this contribution, we use a computational network model to demonstrate that the experimentally observed features of odor coding in PNs can be reproduced by varying lateral inhibition and gain control in an otherwise unchanged AL network. We show that odor coding in the l-ACT supports detection and accurate identification of weak odor traces at the expense of concentration sensitivity, while odor coding in the m-ACT provides the basis for the computation and following of concentration gradients but provides weaker discrimination power. Both coding strategies are mutually exclusive, which creates a tradeoff between detection accuracy and sensitivity. The development of two parallel systems may thus reflect an evolutionary solution to this problem that enables honeybees to achieve both tasks during bee foraging in their natural environment, and which could inspire the development of artificial chemosensory devices for odor-guided navigation in robots.

PACS-1 Mediates Phosphorylation-Dependent Ciliary Trafficking of the CNG Channel in Olfactory Sensory Neurons

PubMed Central

Jenkins, Paul M.; Zhang, Lian; Thomas, Gary; Martens, Jeffrey R.

2009-01-01

Impaired ciliary protein transport in olfactory sensory neurons (OSNs) leads to anosmia, and is a newly recognized clinical manifestation of a class of human disorders called ciliopathies. Surprisingly little is known regarding the mechanisms controlling trafficking to this unique neuronal compartment. Here, we show a novel role for phosphofurin acidic cluster-sorting protein 1 (PACS-1) in the ciliary trafficking of the olfactory CNG channel. PACS-1 is an intracellular sorting protein that mediates its effects through the binding of acidic clusters on cargo protein. This interaction is dependent on CK2 phosphorylation of both PACS-1 and its cargo. We show that CNGB1b contains two putative PACS-1 binding sites, which are phosphorylated by the serine/threonine protein kinase, CK2. Additionally, we show that PACS-1 is expressed in OSNs and interacts in complex with the CNG channel. CK2 inhibition in native OSNs causes a loss of CNG channel from cilia and subsequent olfactory dysfunction, while adenoviral expression of mutant PACS-1 causes similar mislocalization. These results provide a mechanism for the subunit-dependent ciliary trafficking of the CNG channel and offer insight into the mechanisms of ciliary transport. PMID:19710307

Side-Specificity of Olfactory Learning in the Honeybee: Generalization between Odors and Sides

PubMed Central

Sandoz, Jean-Christophe; Menzel, Randolf

2001-01-01

Honeybees (Apis mellifera) can be trained to associate an odor stimulus with a sucrose reward. The neural structures involved in the detection and integration of olfactory stimuli are represented bilaterally in the brain. Little is known about the respective roles of the two sides of the brain in olfactory learning. Does each side learn independently of the other, or do they communicate, and if so, to what extent and at what level of neural integration? We addressed these questions using the proboscis extension response (PER) conditioning paradigm applied in a preparation that allows the separation of the two input sides during olfactory stimulations. Bees conditioned to two odorants A and B, one being learned on each side (A+/B+ training), showed in extinction tests rather unspecific responses: They responded to both odorants on both sides. This could be attributable to either a transfer of the learned information between sides, or to a generalization between odorants on each side. By subjecting bees to conditioning on one side only (A+/0 training), we found that the learned information is indeed transferred between sides. However, when bees were trained explicitly to give opposite values to the two odorants on the two sides (A+B−/B+A− training), they showed clear side-specific response patterns to these odorants. These results are used in the elaboration of a functional model of laterality of olfactory learning and memory processing in the honeybee brain. PMID:11584076

The Pig Olfactory Brain: A Primer

PubMed Central

Feldman, Sanford; Osterberg, Stephen K.

2016-01-01

Despite the fact that pigs are reputed to have excellent olfactory abilities, few studies have examined regions of the pig brain involved in the sense of smell. The present study provides an overview of the olfactory bulb, anterior olfactory nucleus, and piriform cortex of adult pigs using several approaches. Nissl, myelin, and Golgi stains were used to produce a general overview of the organization of the regions and confocal microscopy was employed to examine 1) projection neurons, 2) GABAergic local circuit neurons that express somatostatin, parvalbumin, vasoactive intestinal polypeptide, or calretinin, 3) neuromodulatory fibers (cholinergic and serotonergic), and 4) glia (astrocytes and microglia). The findings revealed that pig olfactory structures are quite large, highly organized and follow the general patterns observed in mammals. PMID:26936231

QSPR models for predicting generator-column-derived octanol/water and octanol/air partition coefficients of polychlorinated biphenyls.

PubMed

Yuan, Jintao; Yu, Shuling; Zhang, Ting; Yuan, Xuejie; Cao, Yunyuan; Yu, Xingchen; Yang, Xuan; Yao, Wu

2016-06-01

Octanol/water (K(OW)) and octanol/air (K(OA)) partition coefficients are two important physicochemical properties of organic substances. In current practice, K(OW) and K(OA) values of some polychlorinated biphenyls (PCBs) are measured using generator column method. Quantitative structure-property relationship (QSPR) models can serve as a valuable alternative method of replacing or reducing experimental steps in the determination of K(OW) and K(OA). In this paper, two different methods, i.e., multiple linear regression based on dragon descriptors and hologram quantitative structure-activity relationship, were used to predict generator-column-derived log K(OW) and log K(OA) values of PCBs. The predictive ability of the developed models was validated using a test set, and the performances of all generated models were compared with those of three previously reported models. All results indicated that the proposed models were robust and satisfactory and can thus be used as alternative models for the rapid assessment of the K(OW) and K(OA) of PCBs. Copyright © 2016 Elsevier Inc. All rights reserved.

Hydrostatic pressure modifies the action of octanol and atropine on frog endplate conductance.

PubMed Central

Ashford, M. L.; Macdonald, A. G.; Wann, K. T.

1984-01-01

The effects of octanol, ethanol and atropine were examined on the time course of decay (tau D) of miniature endplate currents (m.e.p.cs) in the frog neuromuscular junction at normal and high pressure. Octanol (25-100 microM) decreased reversibly the tau D of m.e.p.cs in a dose-dependent manner, 100 microM reducing tau D to 0.39 of the control value. Higher concentrations (200-500 microM) additionally depressed the amplitude of m.e.p.cs. Hydrostatic pressure (3.19 and 5.25 MPa) reduced the tau D of octanol (25-100 microM)-shortened m.e.p.cs. Thus 3.19 MPa and 5.25 MPa reduced the tau D in the presence of 100 microM octanol to 0.75 and 0.78 of the octanol treated values. This effect was not completely reversed on decompression. The m.e.p.c. amplitude is reversibly decreased by pressure in the presence of octanol. Hydrostatic pressure (3.19-15.55 MPa) did not modify the effect of ethanol on tau D. At 10.40 and 15.55 MPa the tau D was increased equally in the absence or presence of ethanol. Atropine (60 microM) reduced the tau D and amplitude of m.e.p.cs to 0.33 and 0.63 of the control values. These effects were completely reversible. Hydrostatic pressure (3.19 and 5.25 MPa) reduced the tau D of atropine-shortened m.e.p.cs to 0.82 and 0.77 of the atropine-treated values respectively. This effect was not completely reversed on decompression. Hydrostatic pressure also reversibly depressed the amplitude of atropine-treated m.e.p.cs. The implications of these drug-hydrostatic pressure interactions are discussed. PMID:6333262

Immunocytochemistry of the olfactory marker protein.

PubMed

Monti-Graziadei, G A; Margolis, F L; Harding, J W; Graziadei, P P

1977-12-01

The olfactory marker protein has been localized, by means of immunohistochemical techniques in the primary olfactory neurons of mice. The olfactory marker protein is not present in the staminal cells of the olfactory neuroepithelium, and the protein may be regarded as indicative of the functional stage of the neurons. Our data indicate that the olfactory marker protein is present in the synaptic terminals of the olfactory neurons at the level of the olfactory bulb glomeruli. The postsynaptic profiles of both mitral and periglomerular cells are negative.

Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions

PubMed Central

Chu, Sao-Yu; Wang, Chun-Han; Lin, I-Ya

2017-01-01

Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry. PMID:28448523

Giant Olfactory Meningiomas

PubMed Central

d'Avella, Domenico; Salpietro, Francesco M.; Alafaci, Cetty; Tomasello, Francesco

1999-01-01

Olfactory groove meningiomas may attain surprisingly large size. The subfrontal approach is currently the route preferred by most neurosurgeons for their excision. The pterional-transsylvian route represents an alternate exposure for microsurgery of frontobasal tumors. Although this approach has been already described for olfactory meningiomas, tumors of giant size were not specifically addressed in the literature. We report the application of the pterional-transsylvian approach in six patients with giant olfactory meningiomas. This series is unique because it includes only patients with tumors exceeding 6 cm in diameter with bilateral symmetrical development. A radical removal was achieved in all patients and all of them made a full recovery. To investigate the relevance of the pterional-transsylvian approach for minimizing surgical morbidity, a magnetic resonance imaging protocol was designed to characterize even subtle postoperative frontal lobe structural changes. These changes, limited to the frontal lobe ipsilateral to exposure and localized in specific anatomical domains of the prefrontal area, included cystic degenerative alterations, parenchymal gliosis, and associated persistent white matter edema. Results from the present series strengthen the usefulness of the pterional-transsylvian approach as a safe surgical route for lesions affecting the anterior skull base, even with huge bilateral symmetrical expansion, such as giant olfactory meningiomas. ImagesFigure 1Figure 2Figure 3p26-bFigure 4p27-bFigure 5Figure 6Figure 7 PMID:17171078

Ionotropic crustacean olfactory receptors.

PubMed

Corey, Elizabeth A; Bobkov, Yuriy; Ukhanov, Kirill; Ache, Barry W

2013-01-01

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.

Olfactory Sensitivity for Six Predator Odorants in CD-1 Mice, Human Subjects, and Spider Monkeys

PubMed Central

Sarrafchi, Amir; Odhammer, Anna M. E.; Hernandez Salazar, Laura Teresa; Laska, Matthias

2013-01-01

Using a conditioning paradigm, we assessed the olfactory sensitivity of six CD-1 mice (Mus musculus) for six sulfur-containing odorants known to be components of the odors of natural predators of the mouse. With all six odorants, the mice discriminated concentrations <0.1 ppm (parts per million) from the solvent, and with five of the six odorants the best-scoring animals were even able to detect concentrations <1 ppt (parts per trillion). Four female spider monkeys (Ateles geoffroyi) and twelve human subjects (Homo sapiens) tested in parallel were found to detect the same six odorants at concentrations <0.01 ppm, and with four of the six odorants the best-scoring animals and subjects even detected concentrations <10 ppt. With all three species, the threshold values obtained here are generally lower than (or in the lower range of) those reported for other chemical classes tested previously, suggesting that sulfur-containing odorants may play a special role in olfaction. Across-species comparisons showed that the mice were significantly more sensitive than the human subjects and the spider monkeys with four of the six predator odorants. However, the human subjects were significantly more sensitive than the mice with the remaining two odorants. Human subjects and spider monkeys significantly differed in their sensitivity with only two of the six odorants. These comparisons lend further support to the notion that the number of functional olfactory receptor genes or the relative or absolute size of the olfactory bulbs are poor predictors of a species’ olfactory sensitivity. Analysis of odor structure–activity relationships showed that in both mice and human subjects the type of alkyl rest attached to a thietane and the type of oxygen moiety attached to a thiol significantly affected olfactory sensitivity. PMID:24278296

EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans.

PubMed

Shen, Yu; Zhang, Jiangwen; Calarco, John A; Zhang, Yun

2014-10-01

Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. Copyright © 2014 the authors 0270-6474/14/3413364-07$15.00/0.

Evidence for Chemoreception in Squid Olfactory Organ

DTIC Science & Technology

1990-05-29

Positive Responses and Number of Trials Chemical %Positive #of Trials #of Animals 5mM Isethionate 0 (3) 1 5mM Betaine 0 (13) 1 5mM Menthol 0 (2) 1...that the olfactory organ is the site of high chemical sensitivity. Figure 3. Application of the local anesthetic betaine to the olfactory knob

Zincergic innervation from the anterior olfactory nucleus to the olfactory bulb displays plastic responses after mitral cell loss.

PubMed

Airado, Carmen; Gómez, Carmela; Recio, Javier S; Baltanás, Fernando C; Weruaga, Eduardo; Alonso, José R

2008-12-01

Zinc ions are selectively accumulated in certain neurons (zinc-enriched neurons). The mouse olfactory bulb is richly innervated by zinc-enriched terminals. Here, the plasticity of the zincergic system was studied in the olfactory bulb of the Purkinje Cell Degeneration mutant mouse, an animal with specific postnatal neurodegeneration of the main projection neurons of the olfactory bulb. The analysis focused particularly on the anterior olfactory nucleus since most centrifugal afferents coming to the olfactory bulb arise from this structure. Zinc-enriched terminals in the olfactory bulb and zinc-enriched somata in the anterior olfactory nucleus were visualized after selenite injections. Immunohistochemistry against the vesicular zinc transporter was also carried out to confirm the distribution pattern of zinc-enriched terminals in the olfactory bulb. The mutant mice showed a clear reorganization of zincergic centrifugal projections from the anterior olfactory nucleus to the olfactory bulb. First, all zincergic contralateral neurons projecting to the olfactory bulb were absent in the mutant mice. Second, a significant increase in the number of stained somata was detected in the ipsilateral anterior olfactory nucleus. Since no noticeable changes were observed in the zinc-enriched terminals in the olfactory bulb, it is conceivable that mitral cell loss could induce a reorganization of zinc-enriched projections coming from the anterior olfactory nucleus, probably directed at balancing the global zincergic centrifugal modulation. These results show that zincergic anterior olfactory nucleus cells projecting to the olfactory bulb undergo plastic changes to adapt to the loss of mitral cells in the olfactory bulb of Purkinje Cell Degeneration mutant mice.

The Origin, Development and Molecular Diversity of Rodent Olfactory Bulb Glutamatergic Neurons Distinguished by Expression of Transcription Factor NeuroD1.

PubMed

Roybon, Laurent; Mastracci, Teresa L; Li, Joyce; Stott, Simon R W; Leiter, Andrew B; Sussel, Lori; Brundin, Patrik; Li, Jia-Yi

2015-01-01

Production of olfactory bulb neurons occurs continuously in the rodent brain. Little is known, however, about cellular diversity in the glutamatergic neuron subpopulation. In the central nervous system, the basic helix-loop-helix transcription factor NeuroD1 (ND1) is commonly associated with glutamatergic neuron development. In this study, we utilized ND1 to identify the different subpopulations of olfactory bulb glutamategic neurons and their progenitors, both in the embryo and postnatally. Using knock-in mice, transgenic mice and retroviral transgene delivery, we demonstrate the existence of several different populations of glutamatergic olfactory bulb neurons, the progenitors of which are ND1+ and ND1- lineage-restricted, and are temporally and regionally separated. We show that the first olfactory bulb glutamatergic neurons produced - the mitral cells - can be divided into molecularly diverse subpopulations. Our findings illustrate the complexity of neuronal diversity in the olfactory bulb and that seemingly homogenous neuronal populations can consist of multiple subpopulations with unique molecular signatures of transcription factors and expressing neuronal subtype-specific markers.

Odorant responsiveness of embryonic mouse olfactory sensory neurons expressing the odorant receptors S1 or MOR23.

PubMed

Lam, Rebecca S; Mombaerts, Peter

2013-07-01

The mammalian olfactory system has developed some functionality by the time of birth. There is behavioral and limited electrophysiological evidence for prenatal olfaction in various mammalian species. However, there have been no reports, in any mammalian species, of recordings from prenatal olfactory sensory neurons (OSNs) that express a given odorant receptor (OR) gene. Here we have performed patch-clamp recordings from mouse OSNs that express the OR gene S1 or MOR23, using the odorous ligands 2-phenylethyl alcohol or lyral, respectively. We found that, out of a combined total of 20 OSNs from embryos of these two strains at embryonic day (E)16.5 or later, all responded to a cognate odorous ligand. By contrast, none of six OSNs responded to the ligand at E14.5 or E15.5. The kinetics of the odorant-evoked electrophysiological responses of prenatal OSNs are similar to those of postnatal OSNs. The S1 and MOR23 glomeruli in the olfactory bulb are formed postnatally, but the axon terminals of OSNs expressing these OR genes may be synaptically active in the olfactory bulb at embryonic stages. The upper limit of the acquisition of odorant responsiveness for S1 and MOR23 OSNs at E16.5 is consistent with the developmental expression patterns of components of the olfactory signaling pathway. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Identification of Gustatory–Olfactory Flavor Mixtures: Effects of Linguistic Labeling

PubMed Central

2013-01-01

Two experiments, using different ranges and numbers of stimuli, examined how linguistic labels affect the identification of flavor mixtures containing different proportions of sucrose (gustatory flavorant) and citral (olfactory flavorant). Both experiments asked subjects to identify each stimulus as having either “mostly sugar” or “mostly citrus.” In one condition, no labels preceded the flavor stimuli. In another condition, each flavor stimulus followed a label, either SUGAR or CITRUS, which, the subjects were informed, usually though not always named the stronger flavor component; that is, the labels were probabilistically valid. The results of both experiments showed that the labels systematically modified the identification responses: Subjects responded “sugar” or “citrus” more often when the flavor stimulus followed the corresponding label, SUGAR or CITRUS. But the labels hardly affected overall accuracy of identification. Accuracy was possibly limited, however, by both the confusability of the flavor stimuli per se and the way that confusability could limit the opportunity to discern the probabilistic associations between labels and individual flavor stimuli. We describe the results in terms of a decision-theoretic model, in which labels induce shifts in response criteria governing the identification responses, or possibly effect changes in the sensory representations of the flavorants themselves. PMID:23329730

[Studies on the oxidation reaction of octanol-2 with nitric acid by infrared spectroscopy].

PubMed

Zhang, G; Zhao, G; Wang, Y; Zhang, Q; Zhang, S; Lu, F

1998-04-01

In this paper, the reaction process of oxidation of octanol-2 with nitric acid has been studied by IR spectroscopy. It is found that the main components of non-sapoifiable matter are different in different oxidation degrees. The relation between oxidation products and the amount of nitric acid are investigated,the reaction mechanism has also been studied. Experimental results show that the oxidation process of octanol-2 is as follows: first, octanol-2 is oxidated to octanone-2, or to nitrate, nitrite and nitrile copmpounds, then these compounds are reoxidated to caproic acid in the meantime some by-products, such as valeric, enanthic acids are also found in oxidated products.

Morphology of the olfactory system in the predatory mite Phytoseiulus persimilis.

PubMed

van Wijk, Michiel; Wadman, Wytse J; Sabelis, Maurice W

2006-01-01

The predatory mite Phytoseiulus persimilis locates its prey, the two-spotted spider mite, by means of herbivore-induced plant volatiles. The olfactory response to this quantitatively and qualitatively variable source of information is particularly well documented. The mites perform this task with a peripheral olfactory system that consists of just five putative olfactory sensilla that reside in a dorsal field at the tip of their first pair of legs. The receptor cells innervate a glomerular olfactory lobe just ventral of the first pedal ganglion. We have made a 3D reconstruction of the caudal half of the olfactory lobe in adult females. The glomerular organization as well as the glomerular innervation appears conserved across different individuals. The adult females have, by approximation, a 1:1 ratio of olfactory receptor cells to olfactory glomeruli.

Identification and Comparison of Candidate Olfactory Genes in the Olfactory and Non-Olfactory Organs of Elm Pest Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) Based on Transcriptome Analysis.

PubMed

Wang, Yinliang; Chen, Qi; Zhao, Hanbo; Ren, Bingzhong

2016-01-01

The leaf beetle Ambrostoma quadriimpressum (Coleoptera: Chrysomelidae) is a predominant forest pest that causes substantial damage to the lumber industry and city management. However, no effective and environmentally friendly chemical method has been discovered to control this pest. Until recently, the molecular basis of the olfactory system in A. quadriimpressum was completely unknown. In this study, antennae and leg transcriptomes were analyzed and compared using deep sequencing data to identify the olfactory genes in A. quadriimpressum. Moreover, the expression profiles of both male and female candidate olfactory genes were analyzed and validated by bioinformatics, motif analysis, homology analysis, semi-quantitative RT-PCR and RT-qPCR experiments in antennal and non-olfactory organs to explore the candidate olfactory genes that might play key roles in the life cycle of A. quadriimpressum. As a result, approximately 102.9 million and 97.3 million clean reads were obtained from the libraries created from the antennas and legs, respectively. Annotation led to 34344 Unigenes, which were matched to known proteins. Annotation data revealed that the number of genes in antenna with binding functions and receptor activity was greater than that of legs. Furthermore, many pathway genes were differentially expressed in the two organs. Sixteen candidate odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 34 odorant receptors (ORs), 20 inotropic receptors [1] and 2 sensory neuron membrane proteins (SNMPs) and their isoforms were identified. Additionally, 15 OBPs, 9 CSPs, 18 ORs, 6 IRs and 2 SNMPs were predicted to be complete ORFs. Using RT-PCR, RT-qPCR and homology analysis, AquaOBP1/2/4/7/C1/C6, AquaCSP3/9, AquaOR8/9/10/14/15/18/20/26/29/33, AquaIR8a/13/25a showed olfactory-specific expression, indicating that these genes might play a key role in olfaction-related behaviors in A. quadriimpressum such as foraging and seeking. AquaOBP4/C5, AquaOBP4/C5, AquaCSP7

Olfactory dysfunction, olfactory bulb pathology and urban air pollution

PubMed Central

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

Evolution of olfactory receptors.

PubMed

Hoover, Kara C

2013-01-01

Olfactory receptors are a specialized set of receptor cells responsible for the detection of odors. These cells are G protein-coupled receptors and expressed in the cell membranes of olfactory sensory neurons. Once a cell is activated by a ligand, it initiates a signal transduction cascade that produces a nerve impulse to the brain where odor perception is processed. Vertebrate olfactory evolution is characterized by birth-and-death events, a special case of the stochastic continuous time Markov process. Vertebrate fish have three general types of receptor cells (two dedicated to pheromones). Terrestrial animals have different epithelial biology due to the specialized adaptation to detecting airborne odors. Two general classes of olfactory receptor gene reflect the vertebrate marine heritage (Class I) and the derived amphibian, reptile, and mammal terrestrial heritage (Class II). While we know much about olfactory receptor cells, there are still areas where our knowledge is insufficient, such as intra-individual diversity throughout the life time, epigenetic processes acting on olfactory receptors, and association of ligands to specific cells.

The Tritiated Water Skin Barrier Integrity Test: Considerations for Acceptance Criteria with and Without 14C-Octanol.

PubMed

Lehman, Paul A; Beatch, Kacie; Raney, Sam G; Franz, Thomas J

2017-01-01

A study was designed to assess barrier integrity simultaneously using separate compounds (probes) for polar and non-polar pathways through the skin, 3 H 2 O and 14 C-octanol, respectively; and to determine whether the two probe approach could better define barrier integrity. A 5-min dose of water containing 3 H 2 O and 14 C -octanol was applied to ex vivo human skin mounted in Franz diffusion cells. The receptor solution was sampled at 30 min, analyzed for 3 H and 14 C content, and the correlation between water and octanol absorption was determined by statistical tests suitable for non-normally distributed data. This study was conducted on skin from 37 donors with from 3 to 30 replicate skin sections per donor (a total of 426 sections). The correlation between 3 H 2 O and 14 C-octanol absorption was low (Pearson correlation coefficient = 0.3485). The 3 H 2 O absorption cutoff used in this study to select for a normal skin barrier rejected some sections in which 14 C-octanol absorption was within normal limits and accepted others in which 14 C-octanol absorption was abnormally high. The converse was true for 3 H 2 O absorption when the 14 C-octanol-based cutoff was used. The results of the 3 H 2 O test or of similar tests that primarily assess the permeability of polar pathways through the skin may not necessarily provide information relevant to the absorption of highly lipophilic compounds. Octanol, or another molecule that more closely matches the physicochemical attributes of the test compound, may characterize properties of the skin barrier that are more relevant to compounds of low water solubility.

The prevalence of olfactory dysfunction in chronic rhinosinusitis.

PubMed

Kohli, Preeti; Naik, Akash N; Harruff, E Emily; Nguyen, Shaun A; Schlosser, Rodney J; Soler, Zachary M

2017-02-01

Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study were to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. A total of 47 articles were included in a systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin' Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96 ± 7.11 using the 40-item Smell Identification Test, 8.60 ± 2.81 using the Brief Smell Identification Test, 21.96 ± 8.88 using total Sniffin' Sticks score, 5.65 ± 1.51 using Sniffin' Sticks-Threshold, 9.21 ± 4.63 using Sniffin' Sticks-Discrimination, 9.47 ± 3.92 using Sniffin' Sticks-Identification, and 8.90 ± 5.14 using the Questionnaire for Olfactory Disorders-Negative Statements. In CRS populations, a significant percentage of patients experience olfactory dysfunction, and mean olfactory scores are within the dysosmic range. Laryngoscope, 2016 127:309-320, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

The Prevalence of Olfactory Dysfunction in Chronic Rhinosinusitis

PubMed Central

Kohli, Preeti; Naik, Akash N.; Harruff, E. Emily; Nguyen, Shaun A.; Schlosser, Rodney J.; Soler, Zachary M.

2016-01-01

Objective Many studies have reported that olfactory dysfunction frequently occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and degree of olfactory loss has not been systematically studied. The aims of this study are to use combined data to report the prevalence of olfactory dysfunction and to calculate weighted averages of olfactory test scores in CRS patients. Data Sources A search was conducted in PubMed and Scopus, following the methods of Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Review Methods Studies reporting the prevalence of olfactory dysfunction using objective measures or olfactory test scores using validated scales were included. Results A total of 47 articles were included in systematic review and 35 in the pooled data analysis. The prevalence of olfactory dysfunction in chronic rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test, 67.0% using the 40-item Smell Identification Test, and 78.2% using the total Sniffin’ Sticks score. Weighted averages ± standard deviation of olfactory test scores were 25.96±7.11 using the 40-item Smell Identification Test, 8.60±2.81 using the Brief Smell Identification Test, 21.96±8.88 using total Sniffin’ sticks score, 5.65±1.51 using Sniffin’ Sticks threshold, 9.21±4.63 using Sniffin’ Sticks discrimination, 9.47±3.92 using Sniffin’ Sticks Identification, and 8.90±5.14 using the questionnaire for olfactory disorders-negative statements. Conclusion In chronic rhinosinusitis populations, a significant percentage of patients experience olfactory dysfunction and mean olfactory scores are within the dysosmic range. PMID:27873345

Octanol-water partition coefficients for predicting the effects of tannins in ruminant nutrition.

PubMed

Mueller-Harvey, Irene; Mlambo, Victor; Sikosana, Joe L N; Smith, Tim; Owen, Emyr; Brown, Ron H

2007-07-11

Tannins can cause beneficial or harmful nutritional effects, but their great diversity has until now prevented a rational distinction between tannin structures and their nutritional responses. An attempt has been made to study this problem by examining the octanol-water solubilities of tannins. A relatively simple HPLC method has been developed for screening mixtures of plant tannins for their octanol-water partition coefficients (Kow coefficients). Tannins were isolated from the fruits and leaves of different Acacia, Calliandra, Dichrostachys, and Piliostigma species, which are known to produce beneficial or harmful effects. The Kow coefficients of these tannins ranged from 0.061 to 13.9, average coefficients of variation were 9.2% and recoveries were 107%. Acacia nilotica fruits and leaves had the highest Kow coefficients, that is, 2.0 and 13.9, respectively. These A. nilotica products also have high concentrations of tannins. The combined effects of high octanol solubilities and high tannin concentrations may explain their negative effects on animal nutrition and health. It is known that compounds with high octanol solubilities are more easily absorbed into tissues, and it is, therefore, proposed that such compounds are more likely to cause toxicity problems especially if consumed in large quantities. According to the literature, tannins in human foods tend to have low Kow coefficients, and this was confirmed for the tannins in Piliostigma thonningii fruits. Therefore, unconventional feeds or browse products should be screened not only for their tannin concentrations but also for low octanol-water partition coefficients in order to identify nutritionally safe feeds and to avoid potentially toxic feeds.

Octanol-Water Partition Coefficient from 3D-RISM-KH Molecular Theory of Solvation with Partial Molar Volume Correction.

PubMed

Huang, WenJuan; Blinov, Nikolay; Kovalenko, Andriy

2015-04-30

The octanol-water partition coefficient is an important physical-chemical characteristic widely used to describe hydrophobic/hydrophilic properties of chemical compounds. The partition coefficient is related to the transfer free energy of a compound from water to octanol. Here, we introduce a new protocol for prediction of the partition coefficient based on the statistical-mechanical, 3D-RISM-KH molecular theory of solvation. It was shown recently that with the compound-solvent correlation functions obtained from the 3D-RISM-KH molecular theory of solvation, the free energy functional supplemented with the correction linearly related to the partial molar volume obtained from the Kirkwood-Buff/3D-RISM theory, also called the "universal correction" (UC), provides accurate prediction of the hydration free energy of small compounds, compared to explicit solvent molecular dynamics [ Palmer , D. S. ; J. Phys.: Condens. Matter 2010 , 22 , 492101 ]. Here we report that with the UC reparametrized accordingly this theory also provides an excellent agreement with the experimental data for the solvation free energy in nonpolar solvent (1-octanol) and so accurately predicts the octanol-water partition coefficient. The performance of the Kovalenko-Hirata (KH) and Gaussian fluctuation (GF) functionals of the solvation free energy, with and without UC, is tested on a large library of small compounds with diverse functional groups. The best agreement with the experimental data for octanol-water partition coefficients is obtained with the KH-UC solvation free energy functional.

Stimulus function in simultaneous discrimination1

PubMed Central

Biederman, Gerald B.

1968-01-01

In discrimination learning, the negativity of the stimulus correlated with nonreinforcement (S−) declines after 100 training trials while the stimulus correlated with reinforcement (S+) is paradoxically more positive with lesser amounts of discrimination training. Training subjects on two simultaneous discrimination tasks revealed a within-subjects overlearning reversal effect, where a more-frequently presented discrimination problem was better learned in reversal than was a discrimination problem presented less frequently during training. PMID:5672254

The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input.

PubMed

He, Chao; Altshuler-Keylin, Svetlana; Daniel, David; L'Etoile, Noelle D; O'Halloran, Damien

2016-10-06

In mammals, olfactory subsystems have been shown to express seven-transmembrane G-protein-coupled receptors (GPCRs) in a one-receptor-one-neuron pattern, whereas in Caenorhabditis elegans, olfactory sensory neurons express multiple G-protein coupled odorant receptors per olfactory sensory neuron. In both mammalian and C. elegans olfactory sensory neurons (OSNs), the process of olfactory adaptation begins within the OSN; this process of negative feedback within the mammalian OSN has been well described in mammals and enables activated OSNs to desensitize their response cell autonomously while attending to odors detected by separate OSNs. However, the mechanism that enables C. elegans to adapt to one odor and attend to another odor sensed by the same olfactory sensory neuron remains unclear. We found that the cyclic nucleotide gated channel subunit CNG-1 is required to promote cross adaptation responses between distinct olfactory cues. This change in sensitivity to a pair of odorants after persistent stimulation by just one of these odors is modulated by the internal nutritional state of the animal, and we find that this response is maintained across a diverse range of food sources for C. elegans. We also reveal that CNG-1 integrates food related cues for exploratory motor output, revealing that CNG-1 functions in multiple capacities to link nutritional information with behavioral output. Our data describes a novel model whereby CNG channels can integrate the coincidence detection of appetitive and olfactory information to set olfactory preferences and instruct behavioral outputs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aqueous solubilities, vapor pressures, and 1-octanol-water partition coefficients for C9-C14 linear alkylbenzenes

USGS Publications Warehouse

Sherblom, P.M.; Gschwend, P.M.; Eganhouse, R.P.

1992-01-01

Measurements and estimates of aqueous solubilities, 1-octanol-water partition coefficients (Kow), and vapor pressures were made for 29 linear alkylbenzenes having alkyl chain lengths of 9-14 carbons. The ranges of values observed were vapor pressures from 0.002 to 0.418 Pa, log Kow, from 6.83 to 9.95, and aqueous solubilities from 4 to 38 nmol??L-1. Measured values exhibited a relationship to both the alkyl chain length and the position of phenyl substitution on the alkyl chain. Measurement of the aqueous concentrations resulting from equilibration of a mixture of alkylbenzenes yielded higher than expected values, indicating cosolute or other interactive effects caused enhanced aqueous concentrations of these compounds. ?? 1992 American Chemical Society.

Appetitive but not aversive olfactory conditioning modifies antennal movements in honeybees

PubMed Central

Cholé, Hanna; Junca, Pierre

2015-01-01

In honeybees, two olfactory conditioning protocols allow the study of appetitive and aversive Pavlovian associations. Appetitive conditioning of the proboscis extension response (PER) involves associating an odor, the conditioned stimulus (CS) with a sucrose solution, the unconditioned stimulus (US). Conversely, aversive conditioning of the sting extension response (SER) involves associating the odor CS with an electric or thermal shock US. Each protocol is based on the measure of a different behavioral response (proboscis versus sting) and both only provide binary responses (extension or not of the proboscis or sting). These limitations render the measure of the acquired valence of an odor CS difficult without testing the animals in a freely moving situation. Here, we studied the effects of both olfactory conditioning protocols on the movements of the antennae, which are crucial sensory organs for bees. As bees’ antennae are highly mobile, we asked whether their movements in response to an odorant change following appetitive or aversive conditioning and if so, do odor-evoked antennal movements contain information about the acquired valence of the CS? We implemented a tracking system for harnessed bees’ antennal movements based on a motion capture principle at a high frequency rate. We observed that differential appetitive conditioning had a strong effect on antennal movements. Bees responded to the reinforced odorant with a marked forward motion of the antennae and a strong velocity increase. Conversely, differential aversive conditioning had no associative effect on antennal movements. Rather than revealing the acquired valence of an odorant, antennal movements may represent a novel conditioned response taking place during appetitive conditioning and may provide a possible advantage to bees when foraging in natural situations. PMID:26572651

Characterization of antennal sensilla, larvae morphology and olfactory genes of Melipona scutellaris stingless bee

PubMed Central

de Carvalho, Washington João; Fujimura, Patrícia Tieme; Bonetti, Ana Maria; Goulart, Luiz Ricardo; Cloonan, Kevin; da Silva, Neide Maria; Araújo, Ester Cristina Borges; Ueira-Vieira, Carlos; Leal, Walter S.

2017-01-01

There is growing evidence in the literature suggesting that caste differentiation in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona, is triggered by environmental signals, particularly a primer pheromone. With the proper amount of food and a chemical stimulus, 25% of females emerge as queens, in agreement with a long-standing “two loci/two alleles model” proposed in the 1950s. We surmised that these larvae must be equipped with an olfactory system for reception of these chemical signals. Here we describe for the first time the diversity of antennal sensilla in adults and the morphology of larvae of M. scutellaris. Having found evidence for putative olfactory sensilla in larvae, we next asked whether olfactory proteins were expressed in larvae. Since the molecular basis of M. scutellaris is still unknown, we cloned olfactory genes encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M. scutellaris cDNA template and primers designed on the basis CSPs and OBPs previously reported from the European honeybee, Apis mellifera. We cloned two CSP and two OBP genes and then attempted to express the proteins encoded by these genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain variable fragment antibody library, we generated anti-MscuOBP8 monoclonal antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed in M. scutellaris larvae and it is located in the mandibular region, thus further supporting the hypothesis of olfactory function in immature stages. Lastly, molecular modeling suggests that MscuOBP8 may function as a carrier of primer pheromones or other ligands. PMID:28423045

Characterization of antennal sensilla, larvae morphology and olfactory genes of Melipona scutellaris stingless bee.

PubMed

Carvalho, Washington João de; Fujimura, Patrícia Tieme; Bonetti, Ana Maria; Goulart, Luiz Ricardo; Cloonan, Kevin; da Silva, Neide Maria; Araújo, Ester Cristina Borges; Ueira-Vieira, Carlos; Leal, Walter S

2017-01-01

There is growing evidence in the literature suggesting that caste differentiation in the stingless bee, Melipona scutellaris, and other bees in the genus Melipona, is triggered by environmental signals, particularly a primer pheromone. With the proper amount of food and a chemical stimulus, 25% of females emerge as queens, in agreement with a long-standing "two loci/two alleles model" proposed in the 1950s. We surmised that these larvae must be equipped with an olfactory system for reception of these chemical signals. Here we describe for the first time the diversity of antennal sensilla in adults and the morphology of larvae of M. scutellaris. Having found evidence for putative olfactory sensilla in larvae, we next asked whether olfactory proteins were expressed in larvae. Since the molecular basis of M. scutellaris is still unknown, we cloned olfactory genes encoding chemosensory proteins (CSP) and odorant-binding proteins (OBPs) using M. scutellaris cDNA template and primers designed on the basis CSPs and OBPs previously reported from the European honeybee, Apis mellifera. We cloned two CSP and two OBP genes and then attempted to express the proteins encoded by these genes. With a recombinant OBP, MscuOBP8, and a combinatorial single-chain variable fragment antibody library, we generated anti-MscuOBP8 monoclonal antibody. By immunohistochemistry we demonstrated that the anti-MscuOBP8 binds specifically to the MscuOBP8. Next, we found evidence that MscuOBP8 is expressed in M. scutellaris larvae and it is located in the mandibular region, thus further supporting the hypothesis of olfactory function in immature stages. Lastly, molecular modeling suggests that MscuOBP8 may function as a carrier of primer pheromones or other ligands.

Expression of calmodulin mRNA in rat olfactory neuroepithelium.

PubMed

Biffo, S; Goren, T; Khew-Goodall, Y S; Miara, J; Margolis, F L

1991-04-01

A calmodulin (CaM) cDNA was isolated by differential hybridization screening of a lambda gt10 library prepared from rat olfactory mucosa. This cDNA fragment, containing most of the open reading frame of the rat CaMI gene, was subcloned and used to characterize steady-state expression of CaM mRNA in rat olfactory neuroepithelium and bulb. Within the bulb mitral cells are the primary neuronal population expressing CaM mRNA. The major CaM mRNA expressed in the olfactory mucosa is 1.7 kb with smaller contributions from mRNAs of 4.0 and 1.4 kb. CaM mRNA was primarily associated with the olfactory neurons and, despite the cellular complexity of the tissue and the known involvement of CaM in diverse cellular processes, was only minimally evident in sustentacular cells, gland cells or respiratory epithelium. Following bulbectomy CaM mRNA declines in the olfactory neuroepithelium as does olfactory marker protein (OMP) mRNA. In contrast to the latter, CaM mRNA makes a partial recovery by one month after surgery. These results, coupled with those from in situ hybridization, indicate that CaM mRNA is expressed in both mature and immature olfactory neurons. The program regulating CaM gene expression in olfactory neurons is distinct from those controlling expression of B50/GAP43 in immature, or OMP in mature, neurons respectively.

MiR-132 regulated olfactory bulb proteins linked to olfactory learning in greater short-nosed fruit bat Cynopterus sphinx.

PubMed

Mukilan, Murugan; Rajathei, David Mary; Jeyaraj, Edwin; Kayalvizhi, Nagarajan; Rajan, Koilmani Emmanuvel

2018-05-30

Earlier, we showed that micro RNA-132 (miR-132) regulate the immediate early genes (IEGs) in the olfactory bulb (OB) of fruit bat Cynopterus sphinx during olfactory learning. This study was designed to examine whether the miR-132 regulate other proteins in OB during olfactory learning. To test this, miR-132 anti-sense oligodeoxynucleotide (AS-ODN) was delivered to the OB and then trained to novel odor. The 2-dimensional gel electrophoresis analysis showed that inhibition of miR-132 altered olfactory training induced expression of 321 proteins. Further, liquid chromatography-mass spectrometry (LC-MS/MS) analysis reveals the identity of differently expressed proteins such as phosphoribosyl transferase domain containing protein (PRTFDC 1), Sorting nexin-8 (SNX8), Creatine kinase B-type (CKB) and Annexin A11 (ANX A11). Among them PRTFDC 1 showing 189 matching peptides with highest sequence coverage (67.0%) and protein-protein interaction analysis showed that PRTFDC 1 is a homolog of hypoxanthine phosphoribosyltransferase-1 (HPRT-1). Subsequent immunohistochemical analysis (IHC) showed that inhibition of miR-132 down-regulated HPRT expression in OB of C. sphinx. In addition, western blot analysis depicts that HPRT, serotonin transporter (SERT), N-methyl-d-asparate (NMDA) receptors (2A,B) were down-regulated, but not altered in OB of non-sense oligodeoxynucleotide (NS-ODN) infused groups. These analyses suggest that miR-132 regulates the process of olfactory learning and memory formation through SERT and NMDA receptors signalling, which is possibly associated with the PRTFDC1-HPRT interaction. Copyright © 2017. Published by Elsevier B.V.

Minimal olfactory perception during sleep: why odor alarms will not work for humans.

PubMed

Carskadon, Mary A; Herz, Rachel S

2004-05-01

To examine olfactory arousal threshold during sleep in comparison to an auditory tone. On night 1, participants rated odor intensity when awake and experienced olfactory stimuli during stage 1 sleep. Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials using the "staircase" threshold-detection method. Electroencephalogram, electrooculogram, electromyogram, electrocardiogram, and respiration were recorded along with behavioral response. An 800-Hz tone was given on trials when odors failed to arouse. Participants slept in individual rooms. Stimulus-delivery systems were operated from a separate room, where an experimenter observed physiologic recordings and behavioral responses. Three healthy men and 3 women aged 20 to 25 years (mean, 22 years). Two odorants, peppermint and pyridine, at 4 concentrations were presented through nasal cannulas using an air-dilution olfactometer. Tones were played over a speaker. Behavioral (button press and oral) responses, electroencephalographic activation, and changes in breathing and heart rate were assessed. Participants responded to odors on 92% of stage 1 sleep trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one third of REM sleep trials. Tones were effective on at least 75% of trials. Heart rate increased significantly only following behavioral responses to odors or tones across sleep stages. The data indicate that human olfaction is not reliably capable of alerting a sleeper.

Disruption of centrifugal inhibition to olfactory bulb granule cells impairs olfactory discrimination.

PubMed

Nunez-Parra, Alexia; Maurer, Robert K; Krahe, Krista; Smith, Richard S; Araneda, Ricardo C

2013-09-03

Granule cells (GCs) are the most abundant inhibitory neuronal type in the olfactory bulb and play a critical role in olfactory processing. GCs regulate the activity of principal neurons, the mitral cells, through dendrodendritic synapses, shaping the olfactory bulb output to other brain regions. GC excitability is regulated precisely by intrinsic and extrinsic inputs, and this regulation is fundamental for odor discrimination. Here, we used channelrhodopsin to stimulate GABAergic axons from the basal forebrain selectively and show that this stimulation generates reliable inhibitory responses in GCs. Furthermore, selective in vivo inhibition of GABAergic neurons in the basal forebrain by targeted expression of designer receptors exclusively activated by designer drugs produced a reversible impairment in the discrimination of structurally similar odors, indicating an important role of these inhibitory afferents in olfactory processing.

Carrier Mediated Distribution System (CAMDIS): a new approach for the measurement of octanol/water distribution coefficients.

PubMed

Wagner, Bjoern; Fischer, Holger; Kansy, Manfred; Seelig, Anna; Assmus, Frauke

2015-02-20

Here we present a miniaturized assay, referred to as Carrier-Mediated Distribution System (CAMDIS) for fast and reliable measurement of octanol/water distribution coefficients, log D(oct). By introducing a filter support for octanol, phase separation from water is facilitated and the tendency of emulsion formation (emulsification) at the interface is reduced. A guideline for the best practice of CAMDIS is given, describing a strategy to manage drug adsorption at the filter-supported octanol/buffer interface. We validated the assay on a set of 52 structurally diverse drugs with known shake flask log D(oct) values. Excellent agreement with literature data (r(2) = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log D(oct) units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log D(oct) range = -0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log D(oc)t. Copyright © 2014 Elsevier B.V. All rights reserved.

PACS-1 mediates phosphorylation-dependent ciliary trafficking of the cyclic-nucleotide-gated channel in olfactory sensory neurons.

PubMed

Jenkins, Paul M; Zhang, Lian; Thomas, Gary; Martens, Jeffrey R

2009-08-26

Impaired ciliary protein transport in olfactory sensory neurons (OSNs) leads to anosmia, and is a newly recognized clinical manifestation of a class of human disorders called ciliopathies. Surprisingly little is known regarding the mechanisms controlling trafficking to this unique neuronal compartment. Here, we show a novel role for phosphofurin acidic cluster-sorting protein 1 (PACS-1) in the ciliary trafficking of the olfactory cyclic-nucleotide-gated (CNG) channel. PACS-1 is an intracellular sorting protein that mediates its effects through the binding of acidic clusters on cargo protein. This interaction is dependent on CK2 phosphorylation of both PACS-1 and its cargo. We show that CNGB1b contains two putative PACS-1 binding sites, which are phosphorylated by the serine/threonine protein kinase, CK2. Additionally, we show that PACS-1 is expressed in OSNs and interacts in complex with the CNG channel. CK2 inhibition in native OSNs causes a loss of CNG channel from cilia and subsequent olfactory dysfunction, while adenoviral expression of mutant PACS-1 causes similar mislocalization. These results provide a mechanism for the subunit-dependent ciliary trafficking of the CNG channel and offer insight into the mechanisms of ciliary transport.

Acetylcholine and Olfactory Perceptual Learning

ERIC Educational Resources Information Center

Wilson, Donald A.; Fletcher, Max L.; Sullivan, Regina M.

2004-01-01

Olfactory perceptual learning is a relatively long-term, learned increase in perceptual acuity, and has been described in both humans and animals. Data from recent electrophysiological studies have indicated that olfactory perceptual learning may be correlated with changes in odorant receptive fields of neurons in the olfactory bulb and piriform…

Synergistic effect of dicarbollide anions in liquid-liquid extraction: a molecular dynamics study at the octanol-water interface.

PubMed

Chevrot, G; Schurhammer, R; Wipff, G

2007-04-28

We report a molecular dynamics study of chlorinated cobalt bis(dicarbollide) anions [(B(9)C(2)H(8)Cl(3))(2)Co](-)"CCD(-)" in octanol and at the octanol-water interface, with the main aim to understand why these hydrophobic species act as strong synergists in assisted liquid-liquid cation extraction. Neat octanol is quite heterogeneous and is found to display dual solvation properties, allowing to well solubilize CCD(-), Cs(+) salts in the form of diluted pairs or oligomers, without displaying aggregation. At the aqueous interface, octanol behaves as an amphiphile, forming either monolayers or bilayers, depending on the initial state and confinement conditions. In biphasic octanol-water systems, CCD(-) anions are found to mainly partition to the organic phase, thus attracting Cs(+) or even more hydrophilic counterions like Eu(3+) into that phase. The remaining CCD(-) anions adsorb at the interface, but are less surface active than at the chloroform interface. Finally, we compare the interfacial behavior of the Eu(BTP)(3)(3+) complex in the absence and in the presence of CCD(-) anions and extractant molecules. It is found that when the CCD(-)'s are concentrated enough, the complex is extracted to the octanol phase. Otherwise, it is trapped at the interface, attracted by water. These results are compared to those obtained with chloroform as organic phase and discussed in the context of synergistic effect of CCD(-) in liquid-liquid extraction, pointing to the importance of dual solvation properties of octanol and of the hydrophobic character of CCD(-) for synergistic extraction of cations.

Physicochemical properties/descriptors governing the solubility and partitioning of chemicals in water-solvent-gas systems. Part 2. Solubility in 1-octanol.

PubMed

Raevsky, O A; Perlovich, G L; Schaper, K-J

2007-01-01

On the basis of octanol solubility data (log S(o)) for 218 structurally diverse solid chemicals it was shown that the exclusive consideration of melting points did not provide satisfactory results in the quantitative prediction of this parameter (s = 0.92). The application of HYBOT physicochemical descriptors separately (s = 0.94) and together with melting points (s = 0.70) in the framework of a common regression model also was not successful, although contributions of volume-related and H-bond terms to solubility in octanol were identified. It was proposed that the main reason for such behaviour was the different crystal lattice interaction of different classes of chemicals. Successful calculations of the solubility in octanol of chemicals of interest were performed on the basis of the experimental solubility of structurally/physicochemically/numerically similar nearest neighbours with consideration of their difference in physicochemical parameters (molecular polarisability, H-bond acceptor and donor factors (s = 0.66)) and of these descriptors together with melting point differences (s = 0.38). Good results were obtained for all compounds having nearest neighbours with sufficient similarity, expressed by Tanimoto indexes, and by distances in the scaled 3D descriptor space. Obviously the success of this approach depends on the size of the database.

Dissipative particle dynamics: Systematic parametrization using water-octanol partition coefficients

NASA Astrophysics Data System (ADS)

Anderson, Richard L.; Bray, David J.; Ferrante, Andrea S.; Noro, Massimo G.; Stott, Ian P.; Warren, Patrick B.

2017-09-01

We present a systematic, top-down, thermodynamic parametrization scheme for dissipative particle dynamics (DPD) using water-octanol partition coefficients, supplemented by water-octanol phase equilibria and pure liquid phase density data. We demonstrate the feasibility of computing the required partition coefficients in DPD using brute-force simulation, within an adaptive semi-automatic staged optimization scheme. We test the methodology by fitting to experimental partition coefficient data for twenty one small molecules in five classes comprising alcohols and poly-alcohols, amines, ethers and simple aromatics, and alkanes (i.e., hexane). Finally, we illustrate the transferability of a subset of the determined parameters by calculating the critical micelle concentrations and mean aggregation numbers of selected alkyl ethoxylate surfactants, in good agreement with reported experimental values.

Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain.

PubMed

Mauelshagen, J

1993-02-01

1. Sensitization and classical odor conditioning of the proboscis extension reflex were functionally analyzed by repeated intracellular recordings from a single identified neuron (PE1-neuron) in the central bee brain. This neuron belongs to the class of "extrinsic cells" arising from the pedunculus of the mushroom bodies and has extensive arborizations in the median and lateral protocerebrum. The recordings were performed on isolated bee heads. 2. Two different series of physiological experiments were carried out with the use of a similar temporal succession of stimuli as in previous behavioral experiments. In the first series, one group of animals was used for a single conditioning trial [conditioned stimulus (CS), carnation; unconditioned stimulus (US), sucrose solution to the antennae and proboscis), a second group was used for sensitization (sensitizing stimulus, sucrose solution to the antennae and/or proboscis), and the third group served as control (no sucrose stimulation). In the second series, a differential conditioning paradigm (paired odor CS+, carnation; unpaired odor CS-, orange blossom) was applied to test the associative nature of the conditioning effect. 3. The PE1-neuron showed a characteristic burstlike odor response before the training procedures. The treatments resulted in different spike-frequency modulations of this response, which were specific for the nonassociative and associative stimulus paradigms applied. During differential conditioning, there are dynamic up and down modulations of spike frequencies and of the DC potentials underlying the responses to the CS+. Overall, only transient changes in the minute range were observed. 4. The results of the sensitization procedures suggest two qualitatively different US pathways. The comparison between sensitization and one-trial conditioning shows differential effects of nonassociative and associative stimulus paradigms on the response behavior of the PE1-neuron. The results of the differential

Olfactory epithelium changes in germfree mice

PubMed Central

François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

2016-01-01

Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

Parallel processing of afferent olfactory sensory information

PubMed Central

Vaaga, Christopher E.

2016-01-01

Key points The functional synaptic connectivity between olfactory receptor neurons and principal cells within the olfactory bulb is not well understood.One view suggests that mitral cells, the primary output neuron of the olfactory bulb, are solely activated by feedforward excitation.Using focal, single glomerular stimulation, we demonstrate that mitral cells receive direct, monosynaptic input from olfactory receptor neurons.Compared to external tufted cells, mitral cells have a prolonged afferent‐evoked EPSC, which serves to amplify the synaptic input.The properties of presynaptic glutamate release from olfactory receptor neurons are similar between mitral and external tufted cells.Our data suggest that afferent input enters the olfactory bulb in a parallel fashion. Abstract Primary olfactory receptor neurons terminate in anatomically and functionally discrete cortical modules known as olfactory bulb glomeruli. The synaptic connectivity and postsynaptic responses of mitral and external tufted cells within the glomerulus may involve both direct and indirect components. For example, it has been suggested that sensory input to mitral cells is indirect through feedforward excitation from external tufted cells. We also observed feedforward excitation of mitral cells with weak stimulation of the olfactory nerve layer; however, focal stimulation of an axon bundle entering an individual glomerulus revealed that mitral cells receive monosynaptic afferent inputs. Although external tufted cells had a 4.1‐fold larger peak EPSC amplitude, integration of the evoked currents showed that the synaptic charge was 5‐fold larger in mitral cells, reflecting the prolonged response in mitral cells. Presynaptic afferents onto mitral and external tufted cells had similar quantal amplitude and release probability, suggesting that the larger peak EPSC in external tufted cells was the result of more synaptic contacts. The results of the present study indicate that the monosynaptic

Immunohistochemical characterization of human olfactory tissue

PubMed Central

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

2011-01-01

Objectives/Hypothesis 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. Study Design An immunohistochemical analysis of human olfactory tissue using a comprehensive battery of proven antibodies. Methods 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 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. Results 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 the esthesioneuroblastoma. Conclusion The extent of human olfactory mucosa at autopsy can easily be delineated as a function of age and neurological disease. The similarities in human vs. rodent OE will enable us to translate knowledge from experimental animals to humans and will extend our understanding of human olfactory pathophysiology. PMID:21792956

Insm1 promotes the transition of olfactory progenitors from apical and proliferative to basal, terminally dividing and neuronogenic.

PubMed

Rosenbaum, Jason N; Duggan, Anne; García-Añoveros, Jaime

2011-02-01

Insm1 is a zinc-finger transcription factor transiently expressed throughout the developing nervous system in late progenitors and nascent neurons. Insm1 is also highly expressed in medulloblastomas and other neuroendocrine tumors. We generated mice lacking the Insm1 gene and used them to elucidate its role in neurogenic proliferation of the embryonic olfactory epithelium. We found that deletion of Insm1 results in more apical cells and fewer nascent and mature neurons. In the embryonic olfactory epithelium of Insm1 mutants we detect fewer basal progenitors, which produce neurons, and more apical progenitors, which at this stage produce additional progenitors. Furthermore, in the mutants we detect fewer progenitors expressing NEUROD1, a marker of terminally dividing, neuronogenic (neuron-producing) progenitors (immediate neuronal precursors), and more progenitors expressing ASCL1, a marker of the transit amplifying progenitors that migrate from the apical to the basal edges of the epithelium while dividing to generate the terminal, neuronogenic progenitors. Finally, with timed administration of nucleoside analogs we demonstrate that the Insm1 mutants contain fewer terminally dividing progenitors at embryonic day 12.5. Altogether, these results suggest a role for Insm1 in promoting the transition of progenitors from apical and proliferative to basal, terminal and neuronogenic. This role appears partially conserved with that of its nematode ortholog, egl-46. The similar effects of Insm1 deletion on progenitors of embryonic olfactory epithelium and cortex point to striking parallels in the development of these neuroepithelia, and particularly between the basal progenitors of olfactory epithelium and the subventricular zone progenitors of cortex.

A distinct entorhinal cortex to hippocampal CA1 direct circuit for olfactory associative learning.

PubMed

Li, Yiding; Xu, Jiamin; Liu, Yafeng; Zhu, Jia; Liu, Nan; Zeng, Wenbo; Huang, Ning; Rasch, Malte J; Jiang, Haifei; Gu, Xiang; Li, Xiang; Luo, Minhua; Li, Chengyu; Teng, Junlin; Chen, Jianguo; Zeng, Shaoqun; Lin, Longnian; Zhang, Xiaohui

2017-04-01

Lateral and medial parts of entorhinal cortex (EC) convey nonspatial 'what' and spatial 'where' information, respectively, into hippocampal CA1, via both the indirect EC layer 2→ hippocampal dentate gyrus→CA3→CA1 and the direct EC layer 3→CA1 paths. However, it remains elusive how the direct path transfers distinct information and contributes to hippocampal learning functions. Here we report that lateral EC projection neurons selectively form direct excitatory synapses onto a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (PCs) in the dorsal CA1 (dCA1), while medial EC neurons uniformly innervate all dCA1 PCs. Optogenetically inactivating the distinct lateral EC-dCA1 connections or the postsynaptic dCA1 calbindin-expressing PC activity slows olfactory associative learning. Moreover, optetrode recordings reveal that dCA1 calbindin-expressing PCs develop more selective spiking responses to odor cues during learning. Thus, our results identify a direct lateral EC→dCA1 circuit that is required for olfactory associative learning.

Hyperlipidemic Diet Causes Loss of Olfactory Sensory Neurons, Reduces Olfactory Discrimination, and Disrupts Odor-Reversal Learning

PubMed Central

Thiebaud, Nicolas; Johnson, Melissa C.; Butler, Jessica L.; Bell, Genevieve A.; Ferguson, Kassandra L.; Fadool, Andrew R.; Fadool, James C.; Gale, Alana M.; Gale, David S.

2014-01-01

Currently, 65% of Americans are overweight, which leads to well-supported cardiovascular and cognitive declines. Little, however, is known concerning obesity's impact on sensory systems. Because olfaction is linked with ingestive behavior to guide food choice, its potential dysfunction during obesity could evoke a positive feedback loop to perpetuate poor ingestive behaviors. To determine the effect of chronic energy imbalance and reveal any structural or functional changes associated with obesity, we induced long-term, diet-induced obesity by challenging mice to high-fat diets: (1) in an obesity-prone (C57BL/6J) and obesity-resistant (Kv1.3−/−) line of mice, and compared this with (2) late-onset, genetic-induced obesity in MC4R−/− mice in which diabetes secondarily precipitates after disruption of the hypothalamic axis. We report marked loss of olfactory sensory neurons and their axonal projections after exposure to a fatty diet, with a concomitant reduction in electro-olfactogram amplitude. Loss of olfactory neurons and associated circuitry is linked to changes in neuronal proliferation and normal apoptotic cycles. Using a computer-controlled, liquid-based olfactometer, mice maintained on fatty diets learn reward-reinforced behaviors more slowly, have deficits in reversal learning demonstrating behavioral inflexibility, and exhibit reduced olfactory discrimination. When obese mice are removed from their high-fat diet to regain normal body weight and fasting glucose, olfactory dysfunctions are retained. We conclude that chronic energy imbalance therefore presents long-lasting structural and functional changes in the operation of the sensory system designed to encode external and internal chemical information and leads to altered olfactory- and reward-driven behaviors. PMID:24828650

Confocal Raman Microscopy for in Situ Measurement of Octanol-Water Partitioning within the Pores of Individual C18-Functionalized Chromatographic Particles.

PubMed

Kitt, Jay P; Harris, Joel M

2015-05-19

Octanol-water partitioning is one of the most widely used predictors of hydrophobicity and lipophilicity. Traditional methods for measuring octanol-water partition coefficients (K(ow)), including shake-flasks and generator columns, require hours for equilibration and milliliter quantities of sample solution. These challenges have led to development of smaller-scale methods for measuring K(ow). Recent advances in microfluidics have produced faster and smaller-volume approaches to measuring K(ow). As flowing volumes are reduced, however, separation of water and octanol prior to measurement and detection in small volumes of octanol phase are especially challenging. In this work, we reduce the receiver volume of octanol-water partitioning measurements from current practice by six-orders-of-magnitude, to the femtoliter scale, by using a single octanol-filled reversed-phase, octadecylsilane-modified (C18-silica) chromatographic particle as a collector. The fluid-handling challenges of working in such small volumes are circumvented by eliminating postequilibration phase separation. Partitioning is measured in situ within the pore-confined octanol phase using confocal Raman microscopy, which is capable of detecting and quantifying a wide variety of molecular structures. Equilibration times are fast (less than a minute) because molecular diffusion is efficient over distance scales of micrometers. The demonstrated amount of analyte needed to carry out a measurement is very small, less than 50 fmol, which would be a useful attribute for drug screening applications or testing of small quantities of environmentally sensitive compounds. The method is tested for measurements of pH-dependent octanol-water partitioning of naphthoic acid, and the results are compared to both traditional shake-flask measurements and sorption onto C18-modified silica without octanol present within the pores.

Honey Bees Modulate Their Olfactory Learning in the Presence of Hornet Predators and Alarm Component.

PubMed

Wang, Zhengwei; Qu, Yufeng; Dong, Shihao; Wen, Ping; Li, Jianjun; Tan, Ken; Menzel, Randolf

2016-01-01

In Southeast Asia the native honey bee species Apis cerana is often attacked by hornets (Vespa velutina), mainly in the period from April to November. During the co-evolution of these two species honey bees have developed several strategies to defend themselves such as learning the odors of hornets and releasing alarm components to inform other mates. However, so far little is known about whether and how honey bees modulate their olfactory learning in the presence of the hornet predator and alarm components of honey bee itself. In the present study, we test for associative olfactory learning of A. cerana in the presence of predator odors, the alarm pheromone component isopentyl acetate (IPA), or a floral odor (hexanal) as a control. The results show that bees can detect live hornet odors, that there is almost no association between the innately aversive hornet odor and the appetitive stimulus sucrose, and that IPA is less well associated with an appetitive stimulus when compared with a floral odor. In order to imitate natural conditions, e.g. when bees are foraging on flowers and a predator shows up, or alarm pheromone is released by a captured mate, we tested combinations of the hornet odor and floral odor, or IPA and floral odor. Both of these combinations led to reduced learning scores. This study aims to contribute to a better understanding of the prey-predator system between A. cerana and V. velutina.

[Octanol preconditioning alleviates mouse cardiomyocyte swelling induced by simulated ischemia/reperfusion challenge in vitro].

PubMed

Luo, Yukun; Fang, Jun; Fan, Lin; Lin, Chaogui; Chen, Zhaoyang; Chen, Lianglong

2012-10-01

To investigate the role of connexin 43-formed hemichannels in cell volume regulation induced by simulated ischemia/reperfusion (SI/R). Mouse cardiomyocytes isolated on a Langendorff apparatus with enzyme solution were aliquoted into control, SI/R and SI/R +octanol groups. Calcein-AM was used to stain the cells and the cell volume was measured with confocal microscope by stack scanning. Trypan blue was used to measure the cell viability after the treatments. Calcein-AM staining and cofocal microscopy yielded stable and reproducible results for cell volume measurement. Mouse cardiomyocytes subjected to simulated SI/R showed obvious cell swelling as compared with the control cells [(126∓6)% vs 100%, P<0.05], and octanol preconditioning significantly attenuated the cell swelling [(113∓6)%, P<0.05]. SI/R caused a significant reduction of the cell viability compared to the control cells [(19∓2)% vs (45∓3)%, P<0.01], and octanol preconditioning obviously reduced the viability of the cells with SI/R challenge [(31∓2)%, P<0.01]. Connexin 43-formed hemichannels are involved in the regulation of cardiomyocyte volumes induced by SI/R challenge, and octanol can alleviate the cell swelling to enhance the viability of the cardiomyocytes following SI/R.

Viewing Olfactory Affective Responses Through the Sniff Prism: Effect of Perceptual Dimensions and Age on Olfactomotor Responses to Odors

PubMed Central

Ferdenzi, Camille; Fournel, Arnaud; Thévenet, Marc; Coppin, Géraldine; Bensafi, Moustafa

2015-01-01

Sniffing, which is the active sampling of olfactory information through the nasal cavity, is part of the olfactory percept. It is influenced by stimulus properties, affects how an odor is perceived, and is sufficient (without an odor being present) to activate the olfactory cortex. However, many aspects of the affective correlates of sniffing behavior remain unclear, in particular the modulation of volume and duration as a function of odor hedonics. The present study used a wide range of odorants with contrasted hedonic valence to test: (1) which psychophysical function best describes the relationship between sniffing characteristics and odor hedonics (e.g., linear, or polynomial); (2) whether sniffing characteristics are sensitive to more subtle variations in pleasantness than simple pleasant-unpleasant contrast; (3) how sensitive sniffing is to other perceptual dimensions of odors such as odor familiarity or edibility; and (4) whether the sniffing/hedonic valence relationship is valid in other populations than young adults, such as the elderly. Four experiments were conducted, using 16–48 odorants each, and recruiting a total of 102 participants, including a group of elderly people. Results of the four experiments were very consistent in showing that sniffing was sensitive to subtle variations in unpleasantness but not to subtle variations in pleasantness, and that, the more unpleasant the odor, the more limited the spontaneous sampling of olfactory information through the nasal cavity (smaller volume, shorter duration). This also applied, although to a lesser extent, to elderly participants. Relationships between sniffing and other perceptual dimensions (familiarity, edibility) were less clear. It was concluded that sniffing behavior might be involved in adaptive responses protecting the subject from possibly harmful substances. PMID:26635683

Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.

PubMed

Jenkins, Paul M; Hurd, Toby W; Zhang, Lian; McEwen, Dyke P; Brown, R Lane; Margolis, Ben; Verhey, Kristen J; Martens, Jeffrey R

2006-06-20

Nonmotile cilia on olfactory sensory neurons (OSNs) compartmentalize signaling molecules, including odorant receptors and cyclic nucleotide-gated (CNG) channels, allowing for efficient, spatially confined responses to sensory stimuli . Little is known about the mechanisms of the ciliary targeting of olfactory CNG channels, composed of three subunits: CNGA2, CNGA4, and CNGB1b . Recent reports suggest that subunit composition of the retinal CNG channel influences localization, leading to disease . However, the mechanistic role of subunits in properly targeting native olfactory CNG channels remains unclear. Here, we show that heteromeric assembly with CNGB1b, containing a critical carboxy-terminal motif (RVxP), is required for ciliary trafficking of olfactory CNG channels. Movement of proteins within the cilia is governed by intraflagellar transport (IFT), a process that facilitates bidirectional movement of cargo along microtubules. Work in C. elegans has established that heterotrimeric and homodimeric kinesin-2 family members play a critical role in anterograde transport . In mammalian systems, the heterotrimeric KIF3a/KIF3b/KAP-3 complex plays a clear role in IFT; however, no role has been established for KIF17, the mammalian homolog of OSM-3 . Here, we demonstrate that KIF17 is required for olfactory CNG channel targeting, providing novel insights into mechanisms of mammalian ciliary transport.

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

PubMed

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.

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

PubMed

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

Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

PubMed

Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

1984-08-01

A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity.

Alternative measures of lipophilicity: from octanol-water partitioning to IAM retention.

PubMed

Giaginis, Costas; Tsantili-Kakoulidou, Anna

2008-08-01

This review describes lipophilicity parameters currently used in drug design and QSAR studies. After a short historical overview, the complex nature of lipophilicity as the outcome of polar/nonpolar inter- and intramolecular interactions is analysed and considered as the background for the discussion of the different lipophilicity descriptors. The first part focuses on octanol-water partitioning of neutral and ionisable compounds, evaluates the efficiency of predictions and provides a short description of the experimental methods for the determination of distribution coefficients. A next part is dedicated to reversed-phase chromatographic techniques, HPLC and TLC in lipophilicity assessment. The two methods are evaluated for their efficiency to simulate octanol-water and the progress achieved in the refinement of suitable chromatographic conditions, in particular in the field of HPLC, is outlined. Liposomes as direct models of biological membranes are examined and phospolipophilicity is compared to the traditional lipophilicity concept. Difficulties associated with liposome-water partitioning are discussed. The last part focuses on Immobilised Artificial Membrane (IAM) chromatography as an alternative which combines membrane simulation with rapid measurements. IAM chromatographic retention is compared to octanol-water and liposome-water partitioning as well as to reversed-phase retention and its potential to predict biopartitioning and biological activities is discussed.

Proteomic Analysis of the Human Olfactory Bulb.

PubMed

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.

Human Neural Cells Transiently Express Reelin during Olfactory Placode Development

PubMed Central

Antal, M. Cristina; Samama, Brigitte; Ghandour, M. Said; Boehm, Nelly

2015-01-01

Reelin, an extracellular glycoprotein is essential for migration and correct positioning of neurons during development. Since the olfactory system is known as a source of various migrating neuronal cells, we studied Reelin expression in the two chemosensory olfactory systems, main and accessory, during early developmental stages of human foetuses/embryos from Carnegie Stage (CS) 15 to gestational week (GW) 14. From CS 15 to CS 18, but not at later stages, a transient expression of Reelin was detected first in the presumptive olfactory and then in the presumptive vomeronasal epithelium. During the same period, Reelin-positive cells detach from the olfactory/vomeronasal epithelium and migrate through the mesenchyme beneath the telencephalon. Dab 1, an adaptor protein of the Reelin pathway, was simultaneously expressed in the migratory mass from CS16 to CS17 and, at later stages, in the presumptive olfactory ensheathing cells. Possible involvements of Reelin and Dab 1 in the peripheral migrating stream are discussed. PMID:26270645

Olfactory Functioning in First-Episode Psychosis.

PubMed

Kamath, Vidyulata; Lasutschinkow, Patricia; Ishizuka, Koko; Sawa, Akira

2018-04-06

Though olfactory deficits are well-documented in schizophrenia, fewer studies have examined olfactory performance profiles across the psychosis spectrum. The current study examined odor identification, discrimination, and detection threshold performance in first-episode psychosis (FEP) patients diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder with psychotic features, major depression with psychotic features, and other psychotic conditions. FEP patients (n = 97) and healthy adults (n = 98) completed birhinal assessments of odor identification, discrimination, and detection threshold sensitivity for lyral and citralva. Participants also completed measures of anticipatory pleasure, anhedonia, and empathy. Differences in olfactory performances were assessed between FEP patients and controls and within FEP subgroups. Sex-stratified post hoc analyses were employed for a complete analysis of sex differences. Relationships between self-report measures and olfactory scores were also examined. Individuals with psychosis had poorer scores across all olfactory measures when compared to the control group. Within the psychosis cohort, patients with schizophrenia-associated psychosis had poorer odor identification, discrimination, and citralva detection threshold scores relative to controls. In schizophrenia patients, greater olfactory disturbance was associated with increased negative symptomatology, greater self-reported anhedonia, and lower self-reported anticipatory pleasure. Patients with mood-associated psychosis performed comparable to controls though men and women in this cohort showed differential olfactory profiles. These findings indicate that olfactory deficits extend beyond measures of odor identification in FEP with greater deficits observed in schizophrenia-related subgroups of psychosis. Studies examining whether greater olfactory dysfunction confers greater risk for developing schizophrenia relative to other forms of psychosis are

Effects of allocation of attention on habituation to olfactory and visual food stimuli in children.

PubMed

Epstein, Leonard H; Saad, Frances G; Giacomelli, April M; Roemmich, James N

2005-02-15

Responding to food cues may be disrupted by allocating attention to other tasks. We report two experiments examining the effects of allocation of attention on salivary habituation to olfactory plus visual food cues in 8-12-year-old children. In Experiment 1, 42 children were presented with a series of 8 hamburger food stimulus presentations. During each intertrial interval, participants completed a controlled (hard), or automatic (easy) visual memory task, or no task (control). In Experiment 2, 22 children were presented with 10 presentations of a pizza food stimulus and either listened to an audiobook or no audiobook control. Results of Experiment 1 showed group differences in rate of change in salivation (p=0.014). Children in the controlled task did not habituate to repeated food cues, while children in the automatic (p<0.005) or no task (p<0.001) groups decreased responding over time. In Experiment 2, groups differed in the rate of change in salivation (p=0.004). Children in the no audiobook group habituated (p<0.001), while children in the audiobook group did not habituate. Changes in the rate of habituation when attending to non-food stimuli while eating may be a mechanism for increasing energy intake.

Olfactory source localization in the open field using one or both nostrils.

PubMed

Welge-Lussen, A; Looser, G L; Westermann, B; Hummel, T

2014-03-01

This study aims to examine humans ́ abilities to localize odorants within the open field. Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.

Odorant-stimulated phosphoinositide signaling in mammalian olfactory receptor neurons

PubMed Central

Klasen, K.; Corey, E.A.; Kuck, F.; Wetzel, C.H.; Hatt, H.; Ache, B.W.

2009-01-01

Recent evidence has revived interest in the idea that phosphoinositides (PIs) may play a role in signal transduction in mammalian olfactory receptor neurons (ORNs). To provide direct evidence that odorants indeed activate PI signaling in ORNs, we used adenoviral vectors carrying two different fluorescently tagged probes, the pleckstrin homology (PH) domains of phospholipase Cδ1 (PLCδ1) and the general receptor of phosphoinositides (GRP1), to monitor PI activity in the dendritic knobs of ORNs in vivo. Odorants mobilized PI(4,5)P2/IP3 and PI(3,4,5)P3, the substrates and products of PLC and PI3K. We then measured odorant activation of PLC and PI3K in olfactory ciliary-enriched membranes in vitro using a phospholipid overlay assay and ELISAs. Odorants activated both PLC and PI3K in the olfactory cilia within 2 sec of odorant stimulation. Odorant-dependent activation of PLC and PI3K in the olfactory epithelium could be blocked by enzyme-specific inhibitors. Odorants activated PLC and PI3K with partially overlapping specificity. These results provide direct evidence that odorants indeed activate PI signaling in mammalian ORNs in a manner that is consistent with the idea that PI signaling plays a role in olfactory transduction. PMID:19781634

Transient impairment of olfactory threshold in acute multiple sclerosis relapse.

PubMed

Bsteh, Gabriel; Hegen, Harald; Ladstätter, Felix; Berek, Klaus; Amprosi, Matthias; Wurth, Sebastian; Auer, Michael; Di Pauli, Franziska; Deisenhammer, Florian; Lutterotti, Andreas; Berger, Thomas

2018-05-18

Impairment of olfactory threshold is a feature of early and active relapsing remitting multiple sclerosis (RRMS). It predicts inflammatory disease activity and was reported to be transient. However, the timing of onset and resolve of olfactory threshold impairment remains unclear. To prospectively assess the development of olfactory threshold in acute MS relapse over time in comparison to stable MS patients. In a prospective observational design, we measured olfactory threshold by performing the Sniffin' Sticks test (minimum score 0, maximum score 16 reflecting optimal olfactory function) at baseline and after 4, 12 and 24 weeks. We included 30 RRMS patients with acute MS relapse and 30 clinically stable RRMS patients (defined as no relapse within the last 12 months) as a control group. Olfactory threshold was impaired in patients with acute MS relapse at baseline (median difference = -3.5; inter-quartile range [IQR] -4.5- - 2.5; p < 0.001), week 4 (-2.5; IQR -3.0 - -2.0; p < 0.001), week 12 (-1.5; IQR -2.0 - -0.5; p = 0.002) and week 24 (-0.5; IQR -1.0 - 0.0; p = 0.159) compared to stable MS patients. Of note, in relapsing patients in whom disease-modifying treatment was initiated or escalated after relapse, threshold did not differ anymore from stable patients at week 12 (-0.5; IQR -1.0 - 0.5; p = 0.247) and week 24 (0.0; IQR -1.0 - 1.0; p = 0.753). Olfactory threshold impairment seems to be a transient bystander feature of MS relapse. It may be correlated to the level of inflammation within the CNS and might be a useful biomarker in this regard. Copyright © 2018 Elsevier B.V. All rights reserved.

Olfactory Sensitivity and Odor Structure-Activity Relationships for Aliphatic Carboxylic Acids in CD-1 Mice

PubMed Central

Can Güven, Selçuk; Laska, Matthias

2012-01-01

Using a conditioning paradigm, the olfactory sensitivity of CD-1 mice for a homologous series of aliphatic n-carboxylic acids (ethanoic acid to n-octanoic acid) and several of their isomeric forms was investigated. With all 14 odorants, the animals significantly discriminated concentrations as low as 0.03 ppm (parts per million) from the solvent, and with four odorants the best-scoring animals even detected concentrations as low as 3 ppt (parts per trillion). Analysis of odor structure-activity relationships showed that the correlation between olfactory detection thresholds of the mice for the unbranched carboxylic acids and carbon chain length can best be described as a U-shaped function with the lowest threshold values at n-butanoic acid. A significant positive correlation between olfactory detection thresholds and carbon chain length of the carboxylic acids with their branching next to the functional carboxyl group was found. In contrast, no such correlation was found for carboxylic acids with their branching at the distal end of the carbon chain relative to the functional carboxyl group. Finally, a significant correlation was found between olfactory detection thresholds and the position of the branching of the carboxylic acids. Across-species comparisons suggest that mice are more sensitive for short-chained (C2 to C4) aliphatic n-carboxylic acids than other mammalian species, but not for longer-chained ones (C5 to C8). Further comparisons suggest that odor structure-activity relationships are both substance class- and species-specific. PMID:22479594

An evaluation of olfactory function in adults with gastro-esophageal reflux disease.

PubMed

Günbey, Emre; Gören, İbrahim; Ünal, Recep; Yılmaz, Melikşah

2016-01-01

To the best of the authors' knowledge, this study is the first to evaluate the olfactory function of adult patients diagnosed with GERD. The results revealed that adults with GERD have diminished olfactory function. This study aimed to evaluate the olfactory abilities of subjects using the 'Sniffin' Sticks' olfactory test. A total of 35 men and women aged 18-60 years with a diagnosis of GERD and 45 healthy controls were included in the study. The Sniffin' Sticks olfactory test results of the two groups were compared, and the relationship between the study findings and the olfactory parameters was evaluated. The odor threshold (10.1; 9.5, p = 0.016), odor identification (9.6; 8.1, p < 0.001), and odor discrimination (10.7; 8.9, p < 0.001) of the GERD group were significantly lower than those of the control group. A statistically significant positive correlation was detected between the accompanying chronic pharyngitis, chronic sinusitis, and odor parameters. A significant correlation was not detected between the laryngeal findings and the olfactory parameters.

Comparison of 2-Octanol and Tributyl Phosphate in Recovery of Tungsten from Sulfuric-Phosphoric Acid Leach Solution of Scheelite

NASA Astrophysics Data System (ADS)

Liao, Yulong; Zhao, Zhongwei

2018-04-01

Tungsten was recovered from sulfuric-phosphoric acid leach solution of scheelite using 2-octanol and tributyl phosphate (TBP). Approximately 76% of the tungsten and less than 6.2% of the iron were extracted when using 70% 2-octanol, showing good selectivity for tungsten over iron; the tungsten extraction could not be significantly enhanced using a three-stage countercurrent simulation test. Moreover, more than 99.2% of the W and 91.0% of the Fe were extracted when using 70% TBP, showing poor selectivity, but after pretreating the leach solution with iron powder, less than 5.5% of the Fe was extracted. The loaded phases were stripped using deionized water and ammonia solution. The maximum stripping rate of tungsten from loaded 2-octanol was 45.6% when using water, compared with only 13.1% from loaded TBP. Tungsten was efficiently stripped from loaded phases using ammonia solution without formation of Fe(OH)3 precipitate. Finally, a flow sheet for recovery of tungsten with TBP is proposed.

Exercise Is Associated with Lower Long-Term Risk of Olfactory Impairment in Older Adults

PubMed Central

Schubert, Carla R.; Cruickshanks, Karen J.; Nondahl, David M.; Klein, Barbara EK; Klein, Ronald; Fischer, Mary E.

2013-01-01

Importance The prevalence of olfactory impairment is high in older adults and this decline in olfactory ability may pose health and safety risks, affect nutrition and decrease quality of life. It is important to identify modifiable risk factors to reduce the burden of olfactory impairment in aging populations. Objectives To determine if exercise is associated with the 10-year cumulative incidence of olfactory impairment. Design, Setting and Participants Observational longitudinal population-based Epidemiology of Hearing Loss Study. Participants without olfactory impairment (n=1611) were ages 53-97 years at baseline and were followed for up to ten years (1998-2010). Interventions None Main Outcome and Measures Olfaction was measured with the San Diego Odor Identification Test at three examinations (1998-2000, 2003-2005, 2009-2010) of the Epidemiology of Hearing Loss Study. The main outcome was the incidence of olfactory impairment five (2003-2005) or ten (2009-2010) years later and the association of baseline exercise with the long-term risk of developing olfactory impairment. Results The 10-year cumulative incidence of olfactory impairment was 27.6% (95% confidence interval =25.3, 29.9) and rates varied by age and sex; those who were older (Hazard Ratio =1.88, 95% Confidence Interval=1.74, 2.03, for every 5 years) or male (Hazard Ratio=1.27, 95% Confidence Interval=1.00, 1.61) had an increased risk of olfactory impairment. Participants who reported exercising at least once a week long enough to work up a sweat had a decreased risk of olfactory impairment (age and sex adjusted Hazard Ratio= 0.76, 95% CI= 0.60, 0.97). Increasing frequency of exercise was associated with decreasing risk of developing olfactory impairment (p for trend = 0.02). Conclusion and Relevance Regular exercise was associated with lower 10-year cumulative incidence of olfactory impairment. Older adults who exercise may be able to retain olfactory function with age. PMID:24135745

Specific olfactory receptor populations projecting to identified glomeruli in the rat olfactory bulb.

PubMed Central

Jastreboff, P J; Pedersen, P E; Greer, C A; Stewart, W B; Kauer, J S; Benson, T E; Shepherd, G M

1984-01-01

A critical gap exists in our knowledge of the topographical relationship between the olfactory epithelium and olfactory bulb. The present report describes the application to this problem of a method involving horseradish peroxidase conjugated to wheat germ agglutinin. This material was iontophoretically delivered to circumscribed glomeruli in the olfactory bulb and the characteristics and distribution of retrogradely labeled receptor cells were assessed. After discrete injections into small glomerular groups in the caudomedial bulb, topographically defined populations of receptor cells were labeled. Labeled receptor cell somata appeared at several levels within the epithelium. The receptor cell apical dendrites followed a tight helical course towards the surface of the epithelium. The data thus far demonstrate that functional units within the olfactory system may include not only glomeruli as previously suggested but, in addition, a corresponding matrix of receptor cells possessing functional and topographical specificity. Images PMID:6206495

Modern psychophysical tests to assess olfactory function.

PubMed

Eibenstein, A; Fioretti, A B; Lena, C; Rosati, N; Amabile, G; Fusetti, M

2005-07-01

The sense of smell significantly contributes to quality of life. In recent years much progress has been made in understanding the biochemistry, physiology and pathology of the human olfactory system. Olfactory disorders may arise not only from upper airway phlogosis but also from neurodegenerative disease. Hyposmia may precede motor signs in Parkinson's disease and cognitive deficit in Alzheimer's disease. These findings suggest the complementary role of olfactory tests in the diagnosis and management of neurodegenerative diseases. In this report we present a review of modern olfactory tests and their clinical applications. Although rarely employed in routine clinical practice, the olfactory test evaluates the ability of odour identification and is a useful diagnostic tool for olfaction evaluation. Olfactory screening tests are also available. In this work we strongly recommend the importance of an ENT evaluation before the test administration and dissuade from a self-administration of an olfactory test.

Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

PubMed

Strowbridge, Ben W

2010-02-11

In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks. Copyright 2010 Elsevier Inc. All rights reserved.

[Partitioning of taxifolin-iron ions complexes in octanol-water system].

PubMed

Shatalin, Iu V; Shubina, V S

2014-01-01

The composition of taxifolin-iron ions complexes in an octanol-water biphasic system was studied using the method of absorption spectrophotometry. It was found that at pH 5.0 in an aqueous biphasic system the complex of [Tf2 x Fe x (OH)k(H2O)8-k] is present, but at pH 7.0 and 9.0 the complexes of [Tf2 x Fe x (OH)k(H2O)2-k] and [Tf x Fe x OH)k(H2O)4-k] are predominantly observed. The formation of a stable [Tf3 x Fe] complex occurred in octanol phase. The charged iron ion of this complex is surrounded by taxifolin molecules, which shield the iron ion from lipophilic solvent. During transition from water to octanol phase the changes of the composition of complexes are accompanied by reciprocal changes in portion of taxifolin and iron ions in these phases. It was shown that the portion of taxifolin in aqueous solution in the presence of iron ions is increased at high pH values, and the portion of iron ions is minimal at pH 7.0. In addition, the parameters of solubility limits of taxifolin-iron ions complexes in an aqueous solution were determined. The data obtained gain a better understanding of the role of complexation of polyphenol with metal of variable valency in passive transport of flavonoids and metal ions across lipid membranes.

Immobilization of Pseudomonas fluorescens lipase onto magnetic nanoparticles for resolution of 2-octanol.

PubMed

Xun, Er-na; Lv, Xiao-li; Kang, Wei; Wang, Jia-xin; Zhang, Hong; Wang, Lei; Wang, Zhi

2012-10-01

The lipase from Pseudomonas fluorescens (Lipase AK, AKL) was immobilized onto the magnetic Fe(3)O(4) nanoparticles via hydrophobic interaction. Enzyme loading and immobilization yield were determined as 21.4±0.5 mg/g and 49.2±1.8 %, respectively. The immobilized AKL was successfully used for resolution of 2-octanol with vinyl acetate used as acyl donor. Effects of organic solvent, water activity, substrate ratio, and temperature were investigated. Under the optimum conditions, the preferred isomer for AKL is the (R)-2-octanol and the highest enantioselectivity (E=71.5±2.2) was obtained with a higher enzyme activity (0.197±0.01 μmol/mg/min). The results also showed that the immobilized lipase could be easily separated from reaction media by the magnetic steel and remained 89 % of its initial activity as well as the nearly unchanged enantioselectivity after five consecutive cycles, indicating a high stability in practical operation.

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

PubMed Central

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

Olfactory receptor neuron profiling using sandalwood odorants.

PubMed

Bieri, Stephan; Monastyrskaia, Katherine; Schilling, Boris

2004-07-01

The mammalian olfactory system can discriminate between volatile molecules with subtle differences in their molecular structures. Efforts in synthetic chemistry have delivered a myriad of smelling compounds of different qualities as well as many molecules with very similar olfactive properties. One important class of molecules in the fragrance industry are sandalwood odorants. Sandalwood oil and four synthetic sandalwood molecules were selected to study the activation profile of endogenous olfactory receptors when exposed to compounds from the same odorant family. Dissociated rat olfactory receptor neurons were exposed to the sandalwood molecules and the receptor activation studied by monitoring fluxes in the internal calcium concentration. Olfactory receptor neurons were identified that were specifically stimulated by sandalwood compounds. These neurons expressed olfactory receptors that can discriminate between sandalwood odorants with slight differences in their molecular structures. This is the first study in which an important class of perfume compounds was analyzed for its ability to activate endogenous olfactory receptors in olfactory receptor neurons.

Certification by the Karl Fischer method of the water content in SRM 2890, Water Saturated 1-Octanol, and the analysis of associated interlaboratory bias in the measurement process.

PubMed

Margolis, S A; Levenson, M

2000-05-01

The calibration of Karl Fischer instruments and reagents and the compensation for instrumental bias are essential to the accurate measurement of trace levels of water in organic and inorganic chemicals. A stable, nonhygroscopic standard, Water Saturated Octanol, which is compatible with the Karl Fischer reagents, has been prepared. This material, Standard Reference Material (SRM) 2890, is homogeneous and is certified to contain 39.24 +/- 0.85 mg water/mL (expanded uncertainty) of solution (47.3 +/- 1.0 mg water/g solution, expanded uncertainty) at 21.5 degrees C. The solubility of water in -octanol has been shown to be nearly constant between 10 degrees C and 30 degrees C (i.e., within 1% of the value at 21.5 degrees C). The results of an interlaboratory comparison exercise illustrate the utility of SRM 2890 in assessing the accuracy and bias of Karl Fischer instruments and measurements.

The physiological basics of the olfactory neuro-epithelium.

PubMed

Watelet, J B; Katotomichelakis, M; Eloy, P; Danielidis, V

2009-01-01

All living organisms can detect and identify chemical substances in their environment. The olfactory epithelium is covered by a mucus layer which is essential for the function of the olfactory neurons that are directly connected to the brain through the cribriform plate. However, little is known about the composition of this mucus in humans and its significance for the diagnosis of olfactory disorders. The olfactory epithelium consists of four primary cell types, including the olfactory receptor cells essential for odour transduction. This review examines the anatomical, histological and physiological fundamentals of olfactory mucosa. Particular attention is paid to the biochemical environment of the olfactory mucosa that regulates both peri-receptor events and several protective functions.

The Embryonic Septum and Ventral Pallium, New Sources of Olfactory Cortex Cells

PubMed Central

de Carlos, Juan A.

2012-01-01

The mammalian olfactory cortex is a complex structure located along the rostro-caudal extension of the ventrolateral prosencephalon, which is divided into several anatomically and functionally distinct areas: the anterior olfactory nucleus, piriform cortex, olfactory tubercle, amygdaloid olfactory nuclei, and the more caudal entorhinal cortex. Multiple forebrain progenitor domains contribute to the cellular diversity of the olfactory cortex, which is invaded simultaneously by cells originating in distinct germinal areas in the dorsal and ventral forebrain. Using a combination of dye labeling techniques, we identified two novel areas that contribute cells to the developing olfactory cortices, the septum and the ventral pallium, from which cells migrate along a radial and then a tangential path. We characterized these cell populations by comparing their expression of calretinin, calbindin, reelin and Tbr1 with that of other olfactory cell populations. PMID:22984546

Acid-sensing ion channels in mouse olfactory bulb M/T neurons

PubMed Central

Li, Ming-Hua; Liu, Selina Qiuying; Inoue, Koichi; Lan, Jinquan; Simon, Roger P.

2014-01-01

The olfactory bulb contains the first synaptic relay in the olfactory pathway, the sensory system in which odorants are detected enabling these chemical stimuli to be transformed into electrical signals and, ultimately, the perception of odor. Acid-sensing ion channels (ASICs), a family of proton-gated cation channels, are widely expressed in neurons of the central nervous system. However, no direct electrophysiological and pharmacological characterizations of ASICs in olfactory bulb neurons have been described. Using a combination of whole-cell patch-clamp recordings and biochemical and molecular biological analyses, we demonstrated that functional ASICs exist in mouse olfactory bulb mitral/tufted (M/T) neurons and mainly consist of homomeric ASIC1a and heteromeric ASIC1a/2a channels. ASIC activation depolarized cultured M/T neurons and increased their intracellular calcium concentration. Thus, ASIC activation may play an important role in normal olfactory function. PMID:24821964

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

PubMed

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.

The Multibasic Cleavage Site in H5N1 Virus Is Critical for Systemic Spread along the Olfactory and Hematogenous Routes in Ferrets

PubMed Central

Schrauwen, Eefje J. A.; Herfst, Sander; Leijten, Lonneke M.; van Run, Peter; Bestebroer, Theo M.; Linster, Martin; Bodewes, Rogier; Kreijtz, Joost H. C. M.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.; Kuiken, Thijs

2012-01-01

The route by which highly pathogenic avian influenza (HPAI) H5N1 virus spreads systemically, including the central nervous system (CNS), is largely unknown in mammals. Especially, the olfactory route, which could be a route of entry into the CNS, has not been studied in detail. Although the multibasic cleavage site (MBCS) in the hemagglutinin (HA) of HPAI H5N1 viruses is a major determinant of systemic spread in poultry, the association between the MBCS and systemic spread in mammals is less clear. Here we determined the virus distribution of HPAI H5N1 virus in ferrets in time and space—including along the olfactory route—and the role of the MBCS in systemic replication. Intranasal inoculation with wild-type H5N1 virus revealed extensive replication in the olfactory mucosa, from which it spread to the olfactory bulb and the rest of the CNS, including the cerebrospinal fluid (CSF). Virus spread to the heart, liver, pancreas, and colon was also detected, indicating hematogenous spread. Ferrets inoculated intranasally with H5N1 virus lacking an MBCS demonstrated respiratory tract infection only. In conclusion, HPAI H5N1 virus can spread systemically via two different routes, olfactory and hematogenous, in ferrets. This systemic spread was dependent on the presence of the MBCS in HA. PMID:22278228

Structure of the principal olfactory tract.

PubMed

Gil-Carcedo, L M; Vallejo, L A; Gil-Carcedo, E

2000-01-01

Although the purpose and importance of the sense of smell in human beings has not been totally clarified, it is one of the principal information channels in macrosmatic animals. It was the first long-distance information system to have appeared in phylogenetic evolution. The objective of this article is to deepen the knowledge of the pathways that join the olfactory epithelium with the cortical olfaction areas, to better understand olfactory dysfunction in human beings. Differential staining and marking techniques were applied to histologic sections obtained from 155 animals of different species, to study the different connections existing among olfactory tract components. Our study of the connections between the olfactory mucosa and the principal olfactory bulb deserves special mention. The distribution of second neuron connections of the olfactory tract with the central nervous system is quite complex and diffuse. This indicates an interrelation between the sense of smell and a multitude of functions. These connections seem to be of different quantitative importance according to species, but qualitatively they exist in both human beings and other macrosmatic animals.

Reference values of olfactory function for Mexico City inhabitants.

PubMed

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.

The 5-HT1A Receptor and the Stimulus Effects of LSD in the Rat

PubMed Central

Reissig, C.J.; Eckler, J.R.; Rabin, R.A.; Winter, J.C.

2005-01-01

Rationale It has been suggested that the 5-HT1A receptor plays a significant modulatory role in the stimulus effects of the indoleamine hallucinogen lysergic acid diethylamide (LSD). Objectives The present study sought to characterize the effects of several compounds with known affinity for the 5-HT1A receptor on the discriminative stimulus effects of LSD. Methods 12 Male F-344 rats were trained in a two-lever, fixed ratio10, food reinforced task with LSD (0.1 mg/kg; IP; 15 min pretreatment) as a discriminative stimulus. Combination and substitution tests with the 5-HT1A agonists, 8-OH-DPAT, buspirone, gepirone, and ipsapirone, with LSD-induced stimulus control were then performed. The effects of these 5-HT1A ligands were also tested in the presence of the selective 5-HT1A receptor antagonist, WAY-100,635 (0.3 mg/kg; SC; 30 min. pretreatment). Results In combination tests stimulus control by LSD was increased by all 5-HT1A receptor ligands with agonist properties. Similarly, in tests of antagonism, the increase in drug-appropriate responding caused by stimulation of the 5-HT1A receptor was abolished by administration of WAY-100,635. Conclusions These data, obtained using a drug discrimination model of the hallucinogenic effects of LSD, provide support for the hypothesis that the 5-HT1A receptor has a significant modulatory role in the stimulus effects of LSD. PMID:16025319

Individual olfactory perception reveals meaningful nonolfactory genetic information

PubMed Central

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

2015-01-01

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 < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion 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. PMID:26100865

[Posttraumatic anosmia: olfactory event related potentials and MRI evaluation].

PubMed

Liu, Jian-Feng; You, Hui; Ni, Dao-Feng; Zhang, Qiu-Hang; Yang, Da-Zhang; Wang, Na-Ya

2008-03-01

Using olfactory event related potentials (OERP) and magnetic resonance to evaluate olfactory function in patients with posttraumatic anosmia. Twenty four patients with posttraumatic anosmia were reviewed retrospectively. A thorough medical history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials, brain computed tomography scan and magnetic resonance image of olfactory pathway were performed in all patients. Subjective olfactory testing indicated 20 of 24 patients were birhinal anosmia, 2 with right nostril anosmia and left impairment, 2 with left anosmia and right normal. No OERP were obtained in 24 (20 were birhinal, 4 was monorhinal), except 4 cases with single nostril. Magnetic resonance imaging revealed the injures to the olfactory bulbs (100%), rectus gyrus (91.7%), orbital gyrus (67%), olfactory tracts (8%) and temporal lobes (8%). OERP can objectively evaluate posttraumatic olfactory function, and magnetic resonance of olfactory pathway can precisely identify the location and extent of injures.

Alterations of brain grey matter density and olfactory bulb volume in patients with olfactory loss after traumatic brain injury.

PubMed

Han, Pengfei; Winkler, Nicole; Hummel, Cornelia; Hähner, Antje; Gerber, Johannes; Hummel, Thomas

2018-04-27

Olfactory loss and traumatic brain injury (TBI) both lead to anatomical brain alterations in humans. Little research has been done on the structural brain changes for TBI patients with olfactory loss. Using voxel-based morphometry, the grey matter (GM) density was examined for twenty-two TBI patients with hyposmia, twenty-four TBI patients with anosmia, and twenty-two age-matched controls. Olfactory bulb (OB) volumes were measured by manual segmentation of acquired T2 weighted coronal slices using a standardized protocol. Brain lesions in the olfactory relevant areas were also examined for TBI patients. Results showed that patients with anosmia have more frequent lesions in the OB, orbitofrontal cortex (OFC) and the temporal lobe pole, as compared to patients with hyposmia. GM density in the primary olfactory area was decreased in both groups of patients. In addition, compared to controls, patients with anosmia showed GM density reduction in several secondary olfactory eloquent regions, including the gyrus rectus, medial OFC, anterior cingulate cortex, insula, and cerebellum. However, patients with hyposmia showed a lesser degree of GM reduction compared to healthy controls. Smaller OB volumes were found for patients with olfactory loss as compared to controls. TBI patients with anosmia had the smallest OB volumes which were caused by the lesions for OB. In addition, post-TBI duration was negatively correlated with GM density in the secondary olfactory areas in patients with hyposmia, but was positively correlated with GM density in the frontal and temporal gyrus in patients with anosmia. The GM density and OB volume reduction among TBI patients with olfactory loss was largely depend on the location and severity of brain lesions in olfactory relevant regions. Longer post-TBI duration had an impact on brain GM density changes, which indicate a decreased olfactory function in patients with hyposmia and possible compensatory mechanisms in patients with anosmia.

A Closer Look at Acid-Base Olfactory Titrations

ERIC Educational Resources Information Center

Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

2005-01-01

Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

Stimulus Equivalence, Generalization, and Contextual Stimulus Control in Verbal Classes

PubMed Central

Sigurðardóttir, Zuilma Gabriela; Mackay, Harry A; Green, Gina

2012-01-01

Stimulus generalization and contextual control affect the development of equivalence classes. Experiment 1 demonstrated primary stimulus generalization from the members of trained equivalence classes. Adults were taught to match six spoken Icelandic nouns and corresponding printed words and pictures to one another in computerized three-choice matching-to-sample tasks. Tests confirmed that six equivalence classes had formed. Without further training, plural forms of the stimuli were presented in tests for all matching performances. All participants demonstrated virtually errorless performances. In Experiment 2, classifications of the nouns used in Experiment 1 were brought under contextual control. Three nouns were feminine and three were masculine. The match-to-sample training taught participants to select a comparison of the same number as the sample (i.e., singular or plural) in the presence of contextual stimulus A regardless of noun gender. Concurrently, in the presence of contextual stimulus B, participants were taught to select a comparison of the same gender as the sample (i.e., feminine or masculine), regardless of number. Generalization was assessed using a card-sorting test. All participants eventually sorted the cards correctly into gender and number stimulus classes. When printed words used in training were replaced by their picture equivalents, participants demonstrated almost errorless performances. PMID:22754102

Olfactory Fear Conditioning Induces Field Potential Potentiation in Rat Olfactory Cortex and Amygdala

ERIC Educational Resources Information Center

Messaoudi, Belkacem; Granjon, Lionel; Mouly, Anne-Marie; Sevelinges, Yannick; Gervais, Remi

2004-01-01

The widely used Pavlovian fear-conditioning paradigms used for studying the neurobiology of learning and memory have mainly used auditory cues as conditioned stimuli (CS). The present work assessed the neural network involved in olfactory fear conditioning, using olfactory bulb stimulation-induced field potential signal (EFP) as a marker of…

The styryl dye FM1-43 suppresses odorant responses in a subset of olfactory neurons by blocking cyclic nucleotide-gated (CNG) channels.

PubMed

Breunig, Esther; Kludt, Eugen; Czesnik, Dirk; Schild, Detlev

2011-08-12

Many olfactory receptor neurons use a cAMP-dependent transduction mechanism to transduce odorants into depolarizations. This signaling cascade is characterized by a sequence of two currents: a cation current through cyclic nucleotide-gated channels followed by a chloride current through calcium-activated chloride channels. To date, it is not possible to interfere with these generator channels under physiological conditions with potent and specific blockers. In this study we identified the styryl dye FM1-43 as a potent blocker of native olfactory cyclic nucleotide-gated channels. Furthermore, we characterized this substance to stain olfactory receptor neurons that are endowed with cAMP-dependent transduction. This allows optical differentiation and pharmacological interference with olfactory receptor neurons at the level of the signal transduction.

Ultrastructural localization of connexins (Cx36, Cx43, Cx45), glutamate receptors and aquaporin-4 in rodent olfactory mucosa, olfactory nerve and olfactory bulb

PubMed Central

RASH, JOHN E.; DAVIDSON, KIMBERLY G. V.; KAMASAWA, NAOMI; YASUMURA, THOMAS; KAMASAWA, MASAMI; ZHANG, CHUNBO; MICHAELS, ROBIN; RESTREPO, DIEGO; OTTERSEN, OLE P.; OLSON, CARL O.; NAGY, JAMES I.

2006-01-01

Odorant/receptor binding and initial olfactory information processing occurs in olfactory receptor neurons (ORNs) within the olfactory epithelium. Subsequent information coding involves high-frequency spike synchronization of paired mitral/tufted cell dendrites within olfactory bulb (OB) glomeruli via positive feedback between glutamate receptors and closely-associated gap junctions. With mRNA for connexins Cx36, Cx43 and Cx45 detected within ORN somata and Cx36 and Cx43 proteins reported in ORN somata and axons, abundant gap junctions were proposed to couple ORNs. We used freeze-fracture replica immunogold labeling (FRIL) and confocal immunofluorescence microscopy to examine Cx36, Cx43 and Cx45 protein in gap junctions in olfactory mucosa, olfactory nerve and OB in adult rats and mice and early postnatal rats. In olfactory mucosa, Cx43 was detected in gap junctions between virtually all intrinsic cell types except ORNs and basal cells; whereas Cx45 was restricted to gap junctions in sustentacular cells. ORN axons contained neither gap junctions nor any of the three connexins. In OB, Cx43 was detected in homologous gap junctions between almost all cell types except neurons and oligodendrocytes. Cx36 and, less abundantly, Cx45 were present in neuronal gap junctions, primarily at “mixed” glutamatergic/electrical synapses between presumptive mitral/tufted cell dendrites. Genomic analysis revealed multiple miRNA (micro interfering RNA) binding sequences in 3′-untranslated regions of Cx36, Cx43 and Cx45 genes, consistent with cell-type-specific post-transcriptional regulation of connexin synthesis. Our data confirm absence of gap junctions between ORNs, and support Cx36- and Cx45-containing gap junctions at glutamatergic mixed synapses between mitral/tufted cells as contributing to higher-order information coding within OB glomeruli. PMID:16841170

Parallel odor processing by mitral and middle tufted cells in the olfactory bulb.

PubMed

Cavarretta, Francesco; Burton, Shawn D; Igarashi, Kei M; Shepherd, Gordon M; Hines, Michael L; Migliore, Michele

2018-05-16

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations. We have analyzed the functional roles of these pathways by using a morphologically and physiologically realistic three-dimensional model to explore the MC and mTC microcircuits in the glomerular layer and deeper plexiform layer. The model makes several predictions. MCs and mTCs are controlled by similar computations in the glomerular layer but are differentially modulated in deeper layers. The intrinsic properties of mTCs promote their synchronization through a common granule cell input. Finally, the MC and mTC pathways can be coordinated through the deep short-axon cells in providing input to the olfactory cortex. The results suggest how these mechanisms can dynamically select the functional network connectivity to create the overall output of the OB and promote the dynamic synchronization of glomerular units for any given odor stimulus.

Functional Differences between Global Pre- and Postsynaptic Inhibition in the Drosophila Olfactory Circuit.

PubMed

Oizumi, Masafumi; Satoh, Ryota; Kazama, Hokto; Okada, Masato

2012-01-01

The Drosophila antennal lobe is subdivided into multiple glomeruli, each of which represents a unique olfactory information processing channel. In each glomerulus, feedforward input from olfactory receptor neurons (ORNs) is transformed into activity of projection neurons (PNs), which represent the output. Recent investigations have indicated that lateral presynaptic inhibitory input from other glomeruli controls the gain of this transformation. Here, we address why this gain control acts "pre"-synaptically rather than "post"-synaptically. Postsynaptic inhibition could work similarly to presynaptic inhibition with regard to regulating the firing rates of PNs depending on the stimulus intensity. We investigate the differences between pre- and postsynaptic gain control in terms of odor discriminability by simulating a network model of the Drosophila antennal lobe with experimental data. We first demonstrate that only presynaptic inhibition can reproduce the type of gain control observed in experiments. We next show that presynaptic inhibition decorrelates PN responses whereas postsynaptic inhibition does not. Due to this effect, presynaptic gain control enhances the accuracy of odor discrimination by a linear decoder while its postsynaptic counterpart only diminishes it. Our results provide the reason gain control operates "pre"-synaptically but not "post"-synaptically in the Drosophila antennal lobe.

[Odor sensing system and olfactory display].

PubMed

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.

Discrimination between olfactory receptor agonists and non-agonists.

PubMed

Topin, Jérémie; de March, Claire A; Charlier, Landry; Ronin, Catherine; Antonczak, Serge; Golebiowski, Jérôme

2014-08-11

A joint approach combining free-energy calculations and calcium-imaging assays on the broadly tuned human 1G1 olfactory receptor is reported. The free energy of binding of ten odorants was computed by means of molecular-dynamics simulations. This state function allows separating the experimentally determined eight agonists from the two non-agonists. This study constitutes a proof-of-principle for the computational deorphanization of olfactory receptors. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

V1 projection zone signals in human macular degeneration depend on task, not stimulus.

PubMed

Masuda, Yoichiro; Dumoulin, Serge O; Nakadomari, Satoshi; Wandell, Brian A

2008-11-01

We used functional magnetic resonance imaging to assess abnormal cortical signals in humans with juvenile macular degeneration (JMD). These signals have been interpreted as indicating large-scale cortical reorganization. Subjects viewed a stimulus passively or performed a task; the task was either related or unrelated to the stimulus. During passive viewing, or while performing tasks unrelated to the stimulus, there were large unresponsive V1 regions. These regions included the foveal projection zone, and we refer to them as the lesion projection zone (LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ while they performed stimulus-related judgments. In control subjects, where we presented the stimulus only within the peripheral visual field, there was no V1 response in the foveal projection zone in any condition. The difference between JMD and control responses can be explained by hypotheses that have very different implications for V1 reorganization. In controls retinal afferents carry signals indicating the presence of a uniform (zero-contrast) region of the visual field. Deletion of retinal input may 1) spur the formation of new cortical pathways that carry task-dependent signals (reorganization), or 2) unmask preexisting task-dependent cortical signals that ordinarily are suppressed by the deleted signals (no reorganization).

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task, not Stimulus

PubMed Central

Dumoulin, Serge O.; Nakadomari, Satoshi; Wandell, Brian A.

2008-01-01

We used functional magnetic resonance imaging to assess abnormal cortical signals in humans with juvenile macular degeneration (JMD). These signals have been interpreted as indicating large-scale cortical reorganization. Subjects viewed a stimulus passively or performed a task; the task was either related or unrelated to the stimulus. During passive viewing, or while performing tasks unrelated to the stimulus, there were large unresponsive V1 regions. These regions included the foveal projection zone, and we refer to them as the lesion projection zone (LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ while they performed stimulus-related judgments. In control subjects, where we presented the stimulus only within the peripheral visual field, there was no V1 response in the foveal projection zone in any condition. The difference between JMD and control responses can be explained by hypotheses that have very different implications for V1 reorganization. In controls retinal afferents carry signals indicating the presence of a uniform (zero-contrast) region of the visual field. Deletion of retinal input may 1) spur the formation of new cortical pathways that carry task-dependent signals (reorganization), or 2) unmask preexisting task-dependent cortical signals that ordinarily are suppressed by the deleted signals (no reorganization). PMID:18250083

Olfactory cytochrome P-450. Studies with suicide substrates of the haemoprotein.

PubMed Central

Reed, C J; Lock, E A; De Matteis, F

1988-01-01

1. The olfactory epithelium of male hamsters has been found to be extremely active in the cumene hydroperoxide-supported oxidation of tetramethylphenylenediamine, and this peroxidase activity has been shown to be cytochrome P-450-dependent. 2. The interaction of a series of suicide substrates of cytochrome P-450 with the hepatic and olfactory mono-oxygenase systems has been assessed by determination of peroxidase, 7-ethoxycoumarin O-de-ethylase (ECOD) and 7-ethoxyresorufin O-de-ethylase (EROD) activities after treatment in vivo with these compounds. Chloramphenicol, OOS-trimethylphosphorothiolate and two dihydropyridines [DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine) and 4-ethyl DDC (3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine)] all caused similar percentage inhibitions of hepatic and olfactory activities, but the absolute amounts of enzymic activity lost were considerably greater in the latter tissue. In contrast, halothane had little effect upon hepatic cytochrome P-450-dependent reactions, whereas it severely inhibited those of the olfactory epithelium. 3. The time course of loss and recovery of hepatic and olfactory peroxidase, ECOD and EROD activities after a single dose of 4-ethyl DDC was studied. The rates of loss of activity observed were very similar, irrespective of tissue or reaction examined. In the olfactory epithelium, all three activities recovered concurrently and at a rate similar to that of the hepatic peroxidase activity. In contrast, the hepatic de-ethylation of 7-ethoxycoumarin and 7-ethoxy-resorufin recovered significantly more rapidly. 4. It is suggested that this behaviour is due to 4-ethyl DDC acting not only as a suicidal inhibitor but also as an inducer of certain forms of cytochrome P-450 in the liver; in the olfactory epithelium, however, inactivation, but not induction, occurs. Classical inducing agents were reported to have no effect upon olfactory cytochrome P-450, and in the present study neither phenobarbitone

Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

PubMed Central

Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

2016-01-01

Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

Sexual odor preference and dopamine release in the nucleus accumbens by estrous olfactory cues in sexually naïve and experienced male rats.

PubMed

Fujiwara, Masaya; Chiba, Atsuhiko

2018-03-01

Sexual behavior is a natural reward that activates mesolimbic dopaminergic system. Microdialysis studies have shown that extracellular level of dopamine (DA) in the nucleus accumbens (NAcc) significantly increases during copulation in male rats. The NAcc DA level is also known to be increased during the presentation of a sexually receptive female before mating. This rise in DA was probably associated with sexual motivation elicited by incentive stimuli from the receptive female. These microdialysis studies, however, did not thoroughly investigated if olfactory stimuli from estrous females could significantly increase the extracellular DA in the NAcc of male rats. The present study was designed to examine systematically the relationship between the expression of preference for the olfactory stimuli from estrous females and the effects of these stimuli on the extracellular DA levels in the NAcc measured by in vivo microdialysis in male Long-Evans (LE) rats. We used two types of olfactory stimuli, either airborne odors (volatile stimuli) or soiled bedding (volatile plus nonvolatile stimuli). The sexually experienced male rats, which experienced six ejaculations, significantly preferred both of these olfactory stimuli from estrous females as opposed to males. Exposure to these female olfactory stimuli gradually increased extracellular DA in the NAcc, which reached significantly higher level above baseline during the period following the removal of the stimuli although not during the 15-min stimulus presentation period. The sexually naïve male rats, on the other hand, showed neither preference for olfactory stimuli from estrous females nor increase in the NAcc DA after exposure to these stimuli. These data suggest that in male LE rats olfactory stimuli from estrous females in and of themselves can be conditional cues that induce both incentive motivation and a significant increase in the NAcc DA probably as a result of being associated with sexual reward through

Two Parallel Olfactory Pathways for Processing General Odors in a Cockroach

PubMed Central

Watanabe, Hidehiro; Nishino, Hiroshi; Mizunami, Makoto; Yokohari, Fumio

2017-01-01

In animals, sensory processing via parallel pathways, including the olfactory system, is a common design. However, the mechanisms that parallel pathways use to encode highly complex and dynamic odor signals remain unclear. In the current study, we examined the anatomical and physiological features of parallel olfactory pathways in an evolutionally basal insect, the cockroach Periplaneta americana. In this insect, the entire system for processing general odors, from olfactory sensory neurons to higher brain centers, is anatomically segregated into two parallel pathways. Two separate populations of secondary olfactory neurons, type1 and type2 projection neurons (PNs), with dendrites in distinct glomerular groups relay olfactory signals to segregated areas of higher brain centers. We conducted intracellular recordings, revealing olfactory properties and temporal patterns of both types of PNs. Generally, type1 PNs exhibit higher odor-specificities to nine tested odorants than type2 PNs. Cluster analyses revealed that odor-evoked responses were temporally complex and varied in type1 PNs, while type2 PNs exhibited phasic on-responses with either early or late latencies to an effective odor. The late responses are 30–40 ms later than the early responses. Simultaneous intracellular recordings from two different PNs revealed that a given odor activated both types of PNs with different temporal patterns, and latencies of early and late responses in type2 PNs might be precisely controlled. Our results suggest that the cockroach is equipped with two anatomically and physiologically segregated parallel olfactory pathways, which might employ different neural strategies to encode odor information. PMID:28529476

Human olfactory receptor responses to odorants

PubMed Central

Mainland, Joel D; Li, Yun R; Zhou, Ting; Liu, Wen Ling L; Matsunami, Hiroaki

2015-01-01

Although the human olfactory system is capable of discriminating a vast number of odors, we do not currently understand what chemical features are encoded by olfactory receptors. In large part this is due to a paucity of data in a search space covering the interactions of hundreds of receptors with billions of odorous molecules. Of the approximately 400 intact human odorant receptors, only 10% have a published ligand. Here we used a heterologous luciferase assay to screen 73 odorants against a clone library of 511 human olfactory receptors. This dataset will allow other researchers to interrogate the combinatorial nature of olfactory coding. PMID:25977809

Topographic mapping--the olfactory system.

PubMed

Imai, Takeshi; Sakano, Hitoshi; Vosshall, Leslie B

2010-08-01

Sensory systems must map accurate representations of the external world in the brain. Although the physical senses of touch and vision build topographic representations of the spatial coordinates of the body and the field of view, the chemical sense of olfaction maps discontinuous features of chemical space, comprising an extremely large number of possible odor stimuli. In both mammals and insects, olfactory circuits are wired according to the convergence of axons from sensory neurons expressing the same odorant receptor. Synapses are organized into distinctive spherical neuropils--the olfactory glomeruli--that connect sensory input with output neurons and local modulatory interneurons. Although there is a strong conservation of form in the olfactory maps of mammals and insects, they arise using divergent mechanisms. Olfactory glomeruli provide a unique solution to the problem of mapping discontinuous chemical space onto the brain.

Mechanisms of Regulation of Olfactory Transduction and Adaptation in the Olfactory Cilium

PubMed Central

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 (Ca2+)-activated chloride (CAC) channels, and the dynamics of their respective ligands, cAMP and Ca2+, and it simulates the EOG results obtained under different experimental conditions through changes in the amplitude and duration of cAMP and Ca2+ 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 GPCR

Disrupted Olfactory Integration in Schizophrenia: Functional Connectivity Study.

PubMed

Kiparizoska, Sara; Ikuta, Toshikazu

2017-09-01

Evidence for olfactory dysfunction in schizophrenia has been firmly established. However, in the typical understanding of schizophrenia, olfaction is not recognized to contribute to or interact with the illness. Despite the solid presence of olfactory dysfunction in schizophrenia, its relation to the rest of the illness remains largely unclear. Here, we aimed to examine functional connectivity of the olfactory bulb, olfactory tract, and piriform cortices and isolate the network that would account for the altered olfaction in schizophrenia. We examined the functional connectivity of these specific olfactory regions in order to isolate other brain regions associated with olfactory processing in schizophrenia. Using the resting state functional MRI data from the Center for Biomedical Research Excellence in Brain Function and Mental Illness, we compared 84 patients of schizophrenia and 90 individuals without schizophrenia. The schizophrenia group showed disconnectivity between the anterior piriform cortex and the nucleus accumbens, between the posterior piriform cortex and the middle frontal gyrus, and between the olfactory tract and the visual cortices. The current results suggest functional disconnectivity of olfactory regions in schizophrenia, which may account for olfactory dysfunction and disrupted integration with other sensory modalities in schizophrenia. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Relationship between uninasal anatomy and uninasal olfactory ability.

PubMed

Hornung, D E; Leopold, D A

1999-01-01

To examine the relationship between uninasal anatomy and olfactory ability. A stepwise analysis of variance was used to regress the logarithm of the percentage of correct responses on the Odorant Confusion Matrix (a measure of olfactory ability) against the logarithm of nasal volume measurements determined from computed tomographic scans. Nineteen patients with hyposmia whose olfactory losses were thought to be related to conductive disorders. After correcting for sex differences, a mathematical model was developed in which the volume of 6 regions of the nasal cavity, 6 first-order interactions, and 3 second-order interactions accounted for 97% of the variation in the measure of olfactory ability. Increases in the size of compartments of the nasal cavity around the olfactory cleft generally increase olfactory ability. Also, anatomical differences in the nasal cavities of men and women may account, in part, for sex differences in olfactory ability.

Cortical Feedback Control of Olfactory Bulb Circuits

PubMed Central

Boyd, Alison M.; Sturgill, James F.; Poo, Cindy; Isaacson, Jeffry S.

2013-01-01

SUMMARY Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. PMID:23259951

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

NASA Astrophysics Data System (ADS)

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.

Olfactory acuity in theropods: palaeobiological and evolutionary implications.

PubMed

Zelenitsky, Darla K; Therrien, François; Kobayashi, Yoshitsugu

2009-02-22

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds.

Olfactory acuity in theropods: palaeobiological and evolutionary implications

PubMed Central

Zelenitsky, Darla K.; Therrien, François; Kobayashi, Yoshitsugu

2008-01-01

This research presents the first quantitative evaluation of the olfactory acuity in extinct theropod dinosaurs. Olfactory ratios (i.e. the ratio of the greatest diameter of the olfactory bulb to the greatest diameter of the cerebral hemisphere) are analysed in order to infer the olfactory acuity and behavioural traits in theropods, as well as to identify phylogenetic trends in olfaction within Theropoda. A phylogenetically corrected regression of olfactory ratio to body mass reveals that, relative to predicted values, the olfactory bulbs of (i) tyrannosaurids and dromaeosaurids are significantly larger, (ii) ornithomimosaurs and oviraptorids are significantly smaller, and (iii) ceratosaurians, allosauroids, basal tyrannosauroids, troodontids and basal birds are within the 95% CI. Relative to other theropods, olfactory acuity was high in tyrannosaurids and dromaeosaurids and therefore olfaction would have played an important role in their ecology, possibly for activities in low-light conditions, locating food, or for navigation within large home ranges. Olfactory acuity was the lowest in ornithomimosaurs and oviraptorids, suggesting a reduced reliance on olfaction and perhaps an omnivorous diet in these theropods. Phylogenetic trends in olfaction among theropods reveal that olfactory acuity did not decrease in the ancestry of birds, as troodontids, dromaeosaurids and primitive birds possessed typical or high olfactory acuity. Thus, the sense of smell must have remained important in primitive birds and its presumed decrease associated with the increased importance of sight did not occur until later among more derived birds. PMID:18957367

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

PubMed

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).

Olfactory toxicity in fishes.

PubMed

Tierney, Keith B; Baldwin, David H; Hara, Toshiaki J; Ross, Peter S; Scholz, Nathaniel L; Kennedy, Christopher J

2010-01-21

Olfaction conveys critical environmental information to fishes, enabling activities such as mating, locating food, discriminating kin, avoiding predators and homing. All of these behaviors can be impaired or lost as a result of exposure to toxic contaminants in surface waters. Historically, teleost olfaction studies have focused on behavioral responses to anthropogenic contaminants (e.g., avoidance). More recently, there has been a shift towards understanding the underlying mechanisms and functional significance of contaminant-mediated changes in fish olfaction. This includes a consideration of how contaminants affect the olfactory nervous system and, by extension, the downstream physiological and behavioral processes that together comprise a normal response to naturally occurring stimuli (e.g., reproductive priming or releasing pheromones). Numerous studies spanning several species have shown that ecologically relevant exposures to common pollutants such as metals and pesticides can interfere with fish olfaction and disrupt life history processes that determine individual survival and reproductive success. This represents one of the pathways by which toxic chemicals in aquatic habitats may increasingly contribute to the decline and at-risk status of many commercially and ecologically important fish stocks. Despite our emerging understanding of the threats that pollution poses for chemical communication in aquatic communities, many research challenges remain. These include: (1) the determination of specific mechanisms of toxicity in the fish olfactory sensory epithelium; (2) an understanding of the impacts of complex chemical mixtures; (3) the capacity to assess olfactory toxicity in fish in situ; (4) the impacts of toxins on olfactory-mediated behaviors that are still poorly understood for many fish species; and (5) the connections between sublethal effects on individual fish and the long-term viability of wild populations. This review summarizes and integrates

Effects of isotretinoin on the olfactory function in patients with acne.

PubMed

Kartal, Demet; Yaşar, Mehmet; Kartal, Levent; Özcan, Ibrahim; Borlu, Murat

2017-01-01

Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell.

Evaluating Force Fields for the Computational Prediction of Ionized Arginine and Lysine Side-Chains Partitioning into Lipid Bilayers and Octanol.

PubMed

Sun, Delin; Forsman, Jan; Woodward, Clifford E

2015-04-14

Abundant peptides and proteins containing arginine (Arg) and lysine (Lys) amino acids can apparently permeate cell membranes with ease. However, the mechanisms by which these peptides and proteins succeed in traversing the free energy barrier imposed by cell membranes remain largely unestablished. Precise thermodynamic studies (both theoretical and experimental) on the interactions of Arg and Lys residues with model lipid bilayers can provide valuable clues to the efficacy of these cationic peptides and proteins. We have carried out molecular dynamics simulations to calculate the interactions of ionized Arg and Lys side-chains with the zwitterionic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayer for 10 widely used lipid/protein force fields: CHARMM36/CHARMM36, SLIPID/AMBER99SB-ILDN, OPLS-AA/OPLS-AA, Berger/OPLS-AA, Berger/GROMOS87, Berger/GROMOS53A6, GROMOS53A6/GROMOS53A6, nonpolarizable MARTINI, polarizable MARTINI, and BMW MARTINI. We performed umbrella sampling simulations to obtain the potential of mean force for Arg and Lys side-chains partitioning from water to the bilayer interior. We found significant differences between the force fields, both for the interactions between side-chains and bilayer surface, as well as the free energy cost for placing the side-chain at the center of the bilayer. These simulation results were compared with the Wimley-White interfacial scale. We also calculated the free energy cost for transferring ionized Arg and Lys side-chains from water to both dry and wet octanol. Our simulations reveal rapid diffusion of water molecules into octanol whereby the equilibrium mole fraction of water in the wet octanol phase was ∼25%. Surprisingly, our free energy calculations found that the high water content in wet octanol lowered the water-to-octanol partitioning free energies for cationic residues by only 0.6 to 0.7 kcal/mol.

Olfactory function in chemical workers exposed to acrylate and methacrylate vapors.

PubMed Central

Schwartz, B S; Doty, R L; Monroe, C; Frye, R; Barker, S

1989-01-01

An investigation of the olfactory function of 731 workers at a chemical facility which manufacturers acrylates and methacrylates was undertaken using a standardized quantitative test. In a cross-sectional analysis of the data, no associations of chemical exposure with olfactory test scores were observed. A nested case-control study designed to evaluate the cumulative effects of exposure on olfactory function, however, revealed elevated crude exposure odds ratios (95% confidence interval) of 2.0 (1.1, 3.8) for all workers and 6.0 (1.7, 21.5) for workers who never smoked cigarettes. Logistic regression analysis, adjusting for multiple confounders, revealed exposure odds ratios of 2.8 (1.1, 7.0) and 13.5 (2.1, 87.6) in these same groups, respectively, and a dose-response relationship between olfactory dysfunction and cumulative exposure scores--semi-quantitative indices of lifetime exposure to the acrylates. The data also revealed decreasing exposure odds ratios with increasing duration since last exposure to these chemicals, suggesting that the effects may be reversible. PMID:2784947

Effect of n-octanol in the mobile phase on lipophilicity determination by reversed-phase high-performance liquid chromatography on a modified silica column.

PubMed

Benhaim, Deborah; Grushka, Eli

2008-10-31

In this study, we show that the addition of n-octanol to the mobile phase improves the chromatographic determination of lipophilicity parameters of xenobiotics (neutral solutes, acidic, neutral and basic drugs) on a Phenomenex Gemini C18 column. The Gemini C18 column is a new generation hybrid silica-based column with an extended pH range capability. The wide pH range (2-12) afforded the examination of basic drugs and acidic drugs in their neutral form. Extrapolated retention factor values, [Formula: see text] , obtained on the above column with the n-octanol-modified mobile phase were very well correlated (1:1 correlation) with literature values of logP (logarithm of the partition coefficient in n-octanol/water) of neutral compounds and neutral drugs (69). In addition, we found good linear correlations between measured [Formula: see text] values and calculated values of the logarithm of the distribution coefficient at pH 7.0 (logD(7.0)) for ionized acidic and basic drugs (r(2)=0.95). The Gemini C18 phase was characterized using the linear solvation energy relationship (LSER) model of Abraham. The LSER system constants for the column were compared to the LSER constants of n-octanol/water extraction system using the Tanaka radar plots. The comparison shows that the two methods are nearly equivalent.

Olfactory discrimination: when vision matters?

PubMed

Demattè, M Luisa; Sanabria, Daniel; Spence, Charles

2009-02-01

Many previous studies have attempted to investigate the effect of visual cues on olfactory perception in humans. The majority of this research has only looked at the modulatory effect of color, which has typically been explained in terms of multisensory perceptual interactions. However, such crossmodal effects may equally well relate to interactions taking place at a higher level of information processing as well. In fact, it is well-known that semantic knowledge can have a substantial effect on people's olfactory perception. In the present study, we therefore investigated the influence of visual cues, consisting of color patches and/or shapes, on people's olfactory discrimination performance. Participants had to make speeded odor discrimination responses (lemon vs. strawberry) while viewing a red or yellow color patch, an outline drawing of a strawberry or lemon, or a combination of these color and shape cues. Even though participants were instructed to ignore the visual stimuli, our results demonstrate that the accuracy of their odor discrimination responses was influenced by visual distractors. This result shows that both color and shape information are taken into account during speeded olfactory discrimination, even when such information is completely task irrelevant, hinting at the automaticity of such higher level visual-olfactory crossmodal interactions.

Impacts of upper respiratory tract disease on olfactory behavior of the Mojave desert tortoise

USGS Publications Warehouse

Germano, Jennifer; Van Zerr, Vanessa E.; Esque, Todd C.; Nussear, Ken E.; Lamberski, Nadine

2014-01-01

Upper respiratory tract disease (URTD) caused by Mycoplasma agassizii is considered a threat to desert tortoise populations that should be addressed as part of the recovery of the species. Clinical signs can be intermittent and include serous or mucoid nasal discharge and respiratory difficulty when nares are occluded. This nasal congestion may result in a loss of the olfactory sense. Turtles are known to use olfaction to identify food items, predators, and conspecifics; therefore, it is likely that URTD affects not only their physical well-being but also their behavior and ability to perform necessary functions in the wild. To determine more specifically the impact nasal discharge might have on free-ranging tortoises (Gopherus agassizii), we compared the responses of tortoises with and without nasal discharge and both positive and negative for M. agassizii antibodies to a visually hidden olfactory food stimulus and an empty control. We found that nasal discharge did reduce sense of smell and hence the ability to locate food. Our study also showed that moderate chronic nasal discharge in the absence of other clinical signs did not affect appetite in desert tortoises.

Olfactory bulb size, odor discrimination and magnetic insensitivity in hummingbirds.

PubMed

Ioalé, P; Papi, F

1989-05-01

Relative olfactory bulb size with respect to telencephalic hemispheres (olfactory ratio) was measured in five species of hummingbirds. Trochiliformes were found to be next to last among 25 avian orders with respect to olfactory bulb development. One hummingbird species, the White-vented Violetear (Colibri serrirostris), was trained in a successive go/no-go discrimination task, and learned to feed or not to feed from a container dependent on the olfactory stimuli associated with it. Test birds learned to discriminate amyl acetate vs. turpentine essence, jasmine essence vs. lavender essence, eucalyptus essence vs. no odor, beta-ionone vs. no odor, carvone vs. eucalyptol. In contrast, 1-phenylethanol vs. beta-ionone discrimination, two odorants which appear similar to humans, was unsuccessful. Using a similar procedure, attempts were made to condition a White-vented Violetear and a Versicolored Emerald (Amazilia versicolor) to magnetic stimuli. The birds were unable to discriminate between a normal field and an oscillating field (square wave, 1 Hz, amplitude +/- 0.40 G).

Olfactory discrimination ability and brain expression of c-fos, Gir and Glut1 mRNA are altered in n-3 fatty acid-depleted rats.

PubMed

Hichami, Aziz; Datiche, Frédérique; Ullah, Sana; Liénard, Fabienne; Chardigny, Jean-Michel; Cattarelli, Martine; Khan, Naim Akhtar

2007-11-22

The long-chain polyunsaturated n-3 fatty acids (n-3 PUFA), particularly docosahexaenoic acid (DHA), are abundantly present in the central nervous system and play an important role in cognitive functions such as learning and memory. We, therefore, investigated the effects of n-3 PUFA-depletion in rats (F2 generation) on the learning of an olfactory discrimination task, progressively acquired within a four-arm maze, and on the mRNA expression of some candidate genes, i.e., c-fos, Gir and glucose transporter (Glut1), which could reflect the level of cerebral activity. We observed that DHA contents were dramatically decreased in the olfactory bulb, the piriform cortex and the neocortex of n-3-depleted rats. Furthermore, the n-3 deficiency resulted in a mild olfactory learning impairment as these rats required more days to master the olfactory task compared to control rats. Real-time RT-PCR experiments revealed that the training induced the expression of c-fos mRNA in all the three regions of the brain whereas Gir and Glut1 mRNA were induced only in olfactory bulb and neocortex. However, such an increase was less marked in the n-3-deficient rats. Taken together, these results allow us to assume that the behavioural impairment in n-3-deficient rats is linked to the depletion of n-3 fatty acids in brain regions processing olfactory cues. Data are discussed in view of the possible role of some of these genes in learning-induced neuronal olfactory plasticity.

Distinct amyloid precursor protein processing machineries of the olfactory system.

PubMed

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.

Nitrogen dioxide pollution exposure is associated with olfactory dysfunction in older US adults

PubMed Central

Adams, Dara R.; Ajmani, Gaurav S.; Pun, Vivian C.; Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.; Suh, Helen H.; Pinto, Jayant M.

2017-01-01

Background Olfactory dysfunction has profound effects on quality of life, physical and social function, and mortality itself. Nitrogen dioxide (NO2) is a pervasive air pollutant that is associated with respiratory diseases. Given the olfactory nerve’s anatomic exposure to airborne pollutants, we investigated the relationship between NO2 exposure and olfactory dysfunction. Methods The ability to identify odors was evaluated using a validated test in respondents from the National Social Life, Health, and Aging Project (NSHAP), a representative probability sample of home-dwelling, older US adults ages 57–85. Exposure to NO2 pollution was assessed using measurements obtained from the US EPA AIRS ambient monitoring site closest to each respondent’s home. We tested the association between NO2 exposure and olfactory dysfunction using multivariate logistic regression. Results Among older adults in the US, 22.6% had impaired olfactory function, defined as ≤ 3 correct (out of 5) on the odor identification test. Median NO2 exposure during the 365 days prior to the interview date was 14.7 ppb (interquartile range [IQR] 10.8–19.7 ppb). An IQR increase in NO2 exposure was associated with increased odds of olfactory dysfunction (OR 1.35, 95% CI: 1.07–1.72), adjusting for age, gender, race/ethnicity, education, cognition, comorbidity, smoking, and season of the home interview (n=1,823). Conclusion We show for the first time that NO2 exposure is associated with olfactory dysfunction in older US adults. These results suggest an important role for NO2 exposure on olfactory dysfunction, and, potentially, nasal disease more broadly. PMID:27620703

OCTANOL/WATER PARTITION COEFFICIENTS AND WATER SOLUBILITIES OF PHTHALATE ESTERS

EPA Science Inventory

Measurements of the octanol/water partition coefficients (K-ow) and water solubilities of di-n-octyl phthalate (DnOP) and di-n-decyl phthalate (DnDP) by the slow-stirring method are reported. The water solubility was also measured for di-n-hexyl phthalate (DnHP). The log K-ow val...

Halogenated methyl-phenyl ethers (anisoles) in the environment: determination of vapor pressures, aqueous solubilities, Henry's law constants, and gas/water- (Kgw), n-octanol/water- (Kow) and gas/n-octanol (Kgo) partition coefficients.

PubMed

Pfeifer, O; Lohmann, U; Ballschmiter, K

2001-11-01

Halogenated methyl-phenyl ethers (methoxybenzenes, anisoles) are ubiquitous organics in the environment although they are not produced in industrial quantities. Modelling the fate of organic pollutants such as halogenated anisoles requires a knowledge of the fundamental physico-chemical properties of these compounds. The isomer-specific separation and detection of 60 of the 134 possible congeners allowing an environmental fingerprinting are reported in this study. The vapor pressure p0(L) of more than 60 and further physico-chemical properties of 26 available congeners are given. Vapor pressures p0(L), water solubilities S(L)W, and n-octanol/water partition coefficients Kow were determined by capillary HR-GC (High Resolution Gas Chromatography) on a non-polar phase and by RP-HPLC (Reversed Phase High Performance Liquid Chromatography) on a C18 phase with chlorobenzenes as reference standards. From these experimental data the Henry's law constants H, and the gas/water Kgw and gas/n-octanol Kgo partition coefficients were calculated. We found that vapor pressures, water solubilities, and n-octanol/water partition coefficients of the halogenated anisoles are close to those of the chlorobenzenes. A similar environmental fate of both groups can, therefore, be predicted.

Apolipoprotein E4 causes early olfactory network abnormalities and short-term olfactory memory impairments.

PubMed

Peng, Katherine Y; Mathews, Paul M; Levy, Efrat; Wilson, Donald A

2017-02-20

While apolipoprotein (Apo) E4 is linked to increased incidence of Alzheimer's disease (AD), there is growing evidence that it plays a role in functional brain irregularities that are independent of AD pathology. However, ApoE4-driven functional differences within olfactory processing regions have yet to be examined. Utilizing knock-in mice humanized to ApoE4 versus the more common ApoE3, we examined a simple olfactory perceptual memory that relies on the transfer of information from the olfactory bulb (OB) to the piriform cortex (PCX), the primary cortical region involved in higher order olfaction. In addition, we have recorded in vivo resting and odor-evoked local field potentials (LPF) from both brain regions and measured corresponding odor response magnitudes in anesthetized young (6-month-old) and middle-aged (12-month-old) ApoE mice. Young ApoE4 compared to ApoE3 mice exhibited a behavioral olfactory deficit coinciding with hyperactive odor-evoked response magnitudes within the OB that were not observed in older ApoE4 mice. Meanwhile, middle-aged ApoE4 compared to ApoE3 mice exhibited heightened response magnitudes in the PCX without a corresponding olfactory deficit, suggesting a shift with aging in ApoE4-driven effects from OB to PCX. Interestingly, the increased ApoE4-specific response in the PCX at middle-age was primarily due to a dampening of baseline spontaneous activity rather than an increase in evoked response power. Our findings indicate that early ApoE4-driven olfactory memory impairments and OB network abnormalities may be a precursor to later network dysfunction in the PCX, a region that not only is targeted early in AD, but may be selectively vulnerable to ApoE4 genotype. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Cortical feedback control of olfactory bulb circuits.

PubMed

Boyd, Alison M; Sturgill, James F; Poo, Cindy; Isaacson, Jeffry S

2012-12-20

Olfactory cortex pyramidal cells integrate sensory input from olfactory bulb mitral and tufted (M/T) cells and project axons back to the bulb. However, the impact of cortical feedback projections on olfactory bulb circuits is unclear. Here, we selectively express channelrhodopsin-2 in olfactory cortex pyramidal cells and show that cortical feedback projections excite diverse populations of bulb interneurons. Activation of cortical fibers directly excites GABAergic granule cells, which in turn inhibit M/T cells. However, we show that cortical inputs preferentially target short axon cells that drive feedforward inhibition of granule cells. In vivo, activation of olfactory cortex that only weakly affects spontaneous M/T cell firing strongly gates odor-evoked M/T cell responses: cortical activity suppresses odor-evoked excitation and enhances odor-evoked inhibition. Together, these results indicate that although cortical projections have diverse actions on olfactory bulb microcircuits, the net effect of cortical feedback on M/T cells is an amplification of odor-evoked inhibition. Copyright © 2012 Elsevier Inc. All rights reserved.

Selective attention to affective value alters how the brain processes olfactory stimuli.

PubMed

Rolls, Edmund T; Grabenhorst, Fabian; Margot, Christian; da Silva, Maria A A P; Velazco, Maria Ines

2008-10-01

How does selective attention to affect influence sensory processing? In a functional magnetic resonance imaging investigation, when subjects were instructed to remember and rate the pleasantness of a jasmine odor, activations were greater in the medial orbito-frontal and pregenual cingulate cortex than when subjects were instructed to remember and rate the intensity of the odor. When the subjects were instructed to remember and rate the intensity, activations were greater in the inferior frontal gyrus. These top-down effects occurred not only during odor delivery but started in a preparation period after the instruction before odor delivery, and continued after termination of the odor in a short-term memory period. Thus, depending on the context in which odors are presented and whether affect is relevant, the brain prepares itself, responds to, and remembers an odor differently. These findings show that when attention is paid to affective value, the brain systems engaged to prepare for, represent, and remember a sensory stimulus are different from those engaged when attention is directed to the physical properties of a stimulus such as its intensity. This differential biasing of brain regions engaged in processing a sensory stimulus depending on whether the cognitive demand is for affect-related versus more sensory-related processing may be an important aspect of cognition and attention. This has many implications for understanding the effects not only of olfactory but also of other sensory stimuli.

Protometric thermometric titrations of sparingly soluble compounds in water in the presence of n-octanol.

PubMed

Burgot, G; Burgot, J-L

2002-10-15

Thermometric titrimetry permits titration of acido-basic compounds in water in the presence of n-octanol. n-Octanol permits the solubilization of protolytes and moreover may also displace the equilibria of the titration reactions. Hydrochlorides of highly insoluble derivatives such as phenothiazine derivatives can be titrated with satisfactory accuracy and precision by sodium hydroxide despite their high pK(a) values. Likewise barbiturate salts can be titrated by hydrochloric acid. In the case of some salts, the methodology may permit the sequential titration of the ion and counter ion. Copyright 2002 Elsevier Science B.V.

Developmental Markers Expressed in Neocortical Layers Are Differentially Exhibited in Olfactory Cortex

PubMed Central

Brunjes, Peter C.; Osterberg, Stephen K.

2015-01-01

Neurons in the cerebral cortex stratify on the basis of their time of origin, axonal terminations and the molecular identities assigned during early development. Olfactory cortices share many feature with the neocortex, including clear lamination and similar cell types. The present study demonstrates that the markers differentially expressed in the projection neurons of the cerebral cortex are also found in olfactory areas. Three of the four regions examined (pars principalis of the anterior olfactory nucleus: AONpP, anterior and posterior piriform cortices: APC, PPC, and the olfactory tubercle) expressed transcription factors found in deep or superficial neurons in the developing neocortex, though large differences were found between areas. For example, while the AONpP, APC and PPC all broadly expressed the deep cortical marker CTIP2, NOR1 (NR4a3) levels were higher in AONpP and DAARP-32 was more prevalent in the APC and PPC. Similar findings were encountered for superficial cortical markers: all three regions broadly expressed CUX1, but CART was only observed in the APC and PPC. Furthermore, regional variations were observed even within single structures (e.g., NOR1 was found primarily in in the dorsal region of AONpP and CART expression was observed in a discrete band in the middle of layer 2 of both the APC and PPC). Experiments using the mitotic marker EDU verified that the olfactory cortices and neocortex share similar patterns of neuronal production: olfactory cells that express markers found in the deep neocortex are produced earlier than those that express superficial makers. Projection neurons were filled by retrograde tracers injected into the olfactory bulb to see if olfactory neurons with deep and superficial markers had different axonal targets. Unlike the cerebral cortex, no specificity was observed: neurons with each of the transcription factors examined were found to be labelled. Together the results indicate that olfactory cortices are complex

Cigarette Smoke Delays Regeneration of the Olfactory Epithelium in Mice.

PubMed

Ueha, Rumi; Ueha, Satoshi; Sakamoto, Takashi; Kanaya, Kaori; Suzukawa, Keigo; Nishijima, Hironobu; Kikuta, Shu; Kondo, Kenji; Matsushima, Kouji; Yamasoba, Tatsuya

2016-08-01

The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.

Office procedures for quantitative assessment of olfactory function.

PubMed

Doty, Richard L

2007-01-01

Despite the importance of the sense of smell for establishing the flavor of foods and beverages, as well as protecting against environmental dangers, this primary sensory system is commonly ignored by the rhinologist. In this article basic issues related to practical measurement of olfactory function in the clinic are described and examples of the application of the two most common paradigms for such measurement--odor identification and detection--are presented. A listing is made of the 27 olfactory tests currently used clinically, along with their strengths and weaknesses. A brief review of common nasosinus-related disorders for which quantitative olfactory testing has been performed is provided. Although many psychophysical tests are available for quantifying olfactory loss, it is apparent that a number are limited in terms of practicality, sensitivity, and reliability. In general, sensitivity and reliability are positively correlated with test length. Given the strengths of the more reliable forced-choice pyschophysical tests and the limitations of electrophysiological tests, the common distinction between "subjective" and "objective" tests is misleading and should not be used. Complete recovery of olfactory function, as measured quantitatively, rarely follows surgical or medical interventions in patients with rhinosinusitis. Given the availability of practical clinical olfactory tests, the modern rhinologist can easily quantify cranial nerve (CN) I function. The application of such tests has led to a new understanding of the effects of nasal disease on olfactory function. Except in cases of total or near-total nasal obstruction, olfactory and airway patency measures usually are unrelated, in accord with the concept that rhinosinusitis primarily influences olfactory function by apoptotic pathological changes within the olfactory neuroepithelium.

Emotional stimulation alters olfactory sensitivity and odor judgment.

PubMed

Pollatos, Olga; Kopietz, Rainer; Linn, Jennifer; Albrecht, Jessica; Sakar, Vehbi; Anzinger, Andrea; Schandry, Rainer; Wiesmann, Martin

2007-07-01

Emotions have a strong influence on the perception of visual and auditory stimuli. Only little is known about the relation between emotional stimulation and olfactory functions. The present study investigated the relationship between the presentation of affective pictures, olfactory functions, and sex. Olfactory performance was assessed in 32 subjects (16 male). Olfactory sensitivity was significantly reduced following unpleasant picture presentation for all subjects and following pleasant picture presentation for male subjects only. Pleasantness and intensity ratings of a neutral suprathreshold odor were related to the valence of the pictures: After unpleasant picture presentation, the odor was rated as less pleasant and more intense, whereas viewing positive pictures induced a significant increase in reported odor pleasantness. We conclude that inducing a negative emotional state reduces olfactory sensitivity. A relation to functional deviations within the primary olfactory cortices is discussed.

Simultaneous Loss of NCKX4 and CNG Channel Desensitization Impairs Olfactory Sensitivity.

PubMed

Ferguson, Christopher H; Zhao, Haiqing

2017-01-04

In vertebrate olfactory sensory neurons (OSNs), Ca 2+ plays key roles in both mediating and regulating the olfactory response. Ca 2+ enters OSN cilia during the response through the olfactory cyclic nucleotide-gated (CNG) channel and stimulates a depolarizing chloride current by opening the olfactory Ca 2+ -activated chloride channel to amplify the response. Ca 2+ also exerts negative regulation on the olfactory transduction cascade, through mechanisms that include reducing the CNG current by desensitizing the CNG channel via Ca 2+ /calmodulin (CaM), to reduce the response. Ca 2+ is removed from the cilia primarily by the K + -dependent Na + /Ca 2+ exchanger 4 (NCKX4), and the removal of Ca 2+ leads to closure of the chloride channel and response termination. In this study, we investigate how two mechanisms conventionally considered negative regulatory mechanisms of olfactory transduction, Ca 2+ removal by NCKX4, and desensitization of the CNG channel by Ca 2+ /CaM, interact to regulate the olfactory response. We performed electro-olfactogram (EOG) recordings on the double-mutant mice, NCKX4 -/- ;CNGB1 ΔCaM , which are simultaneously lacking NCKX4 (NCKX4 -/- ) and Ca 2+ /CaM-mediated CNG channel desensitization (CNGB1 ΔCaM ). Despite exhibiting alterations in various response attributes, including termination kinetics and adaption properties, OSNs in either NCKX4 -/- mice or CNGB1 ΔCaM mice show normal resting sensitivity, as determined by their unchanged EOG response amplitude. We found that OSNs in NCKX4 -/- ;CNGB1 ΔCaM mice displayed markedly reduced EOG amplitude accompanied by alterations in other response attributes. This study suggests that what are conventionally considered negative regulatory mechanisms of olfactory transduction also play a role in setting the resting sensitivity in OSNs. Sensory receptor cells maintain high sensitivity at rest. Although the mechanisms responsible for setting the resting sensitivity of sensory receptor cells are not

Effects of isotretinoin on the olfactory function in patients with acne*

PubMed Central

Kartal, Demet; Yaşar, Mehmet; Kartal, Levent; Özcan, Ibrahim; Borlu, Murat

2017-01-01

Background Isotretinoin is a synthetic analog of vitamin A. Recent studies support a role for retinoic acid in the recovery of olfactory function following injury in mice. Objective This study aimed at determining the effect of isotretinoin on olfactory function in patients who have acne and are otherwise healthy. Methods Forty-five patients (aged 25-40 years) with acne were included in the study. All patients underwent a rhinological examination. Olfactory function was assessed by the Sniffin' Sticks Test. The test was assessed at baseline and in the third month of isotretinoin treatment. Results Isotretinoin improved the performance of patients in the olfactory test. The SST score increased from 8.7±1.09 to 9.5±1.19 (p<0.001), prevalence of hyposmia decreased from 40% to 24% and normosmia increased from 60% to 75% (p=0.059). The percentage of patients whose olfactory function was categorized as "good" increased from 6% to 21.3%. This increase was statistically significant (p<0.05). Study limitations Absence of a control group is one of the limitations of this study. Also, we did not evaluate patients with smell test after stopping isotretinoin treatment. Conclusion We examined the effect of systemic isotretinoin on olfactory function. It can be concluded from the present investigation that isotretinoin therapy improves the sense of smell. PMID:28538877

Olfactory Dysfunction Is Associated with the Intake of Macronutrients in Korean Adults

PubMed Central

Kong, Il Gyu; Kim, So Young; Kim, Min-Su; Park, Bumjung; Kim, Jin-Hwan

2016-01-01

Background Olfactory function can impact food selection. However, few large population-based studies have investigated this effect across different age groups. The objective of this study was to assess the association between subjective olfactory dysfunction (anosmia or hyposmia) and macronutrient intake. Methods A total of 24,990 participants aged 20 to 98 years were evaluated based on data collected through the Korea National Health and Nutrition Examination Survey from 2008 through 2012. Olfactory dysfunction was surveyed using a self-reported questionnaire, and the nutritional status was assessed through a validated 24-hour recall method. Simple and multiple linear regression analyses with complex sampling were performed to evaluate the relationships between olfactory dysfunction and protein intake (daily protein intake/recommended protein intake [%]), carbohydrate intake (daily carbohydrate intake/total calories [%]), and fat intake (daily fat intake/total calories [%]) after adjusting for age, sex, body mass index, income, smoking history, alcohol consumption, and stress level. Results Olfactory dysfunction was reported by 5.4% of Korean adults and was found to be associated with decreased fat consumption (estimated value [EV] of fat intake [%] = -0.57, 95% confidence interval [CI] = -1.13 to -0.13, P = 0.045). A subgroup analysis according to age and sex revealed that among young females, olfactory dysfunction was associated with reduced fat consumption (EV = -2.30, 95% CI = -4.16 to -0.43, P = 0.016) and increased carbohydrate intake (EV = 2.80, 95% CI = 0.55 to 5.05, P = 0.015), and that among middle-aged females, olfactory dysfunction was also associated with reduced fat intake (EV = -1.26, 95% CI = -2.37 to -0.16, P = 0.025). In contrast, among young males, olfactory dysfunction was associated with reduced protein intake (EV = -26.41 95% CI = -45.14 to -7.69, P = 0.006). Conclusion Olfactory dysfunction was associated with reduced fat intake. Moreover

Oxaliplatin-induced neurotoxicity is mediated through gap junction channels and hemichannels and can be prevented by octanol.

PubMed

Kagiava, Alexia; Theophilidis, George; Sargiannidou, Irene; Kyriacou, Kyriacos; Kleopa, Kleopas A

2015-10-01

Oxaliplatin-induced neurotoxicity (OIN) is a common complication of chemotherapy without effective treatment. In order to clarify the mechanisms of both acute and chronic OIN, we used an ex-vivo mouse sciatic nerve model. Exposure to 25 μM oxaliplatin caused a marked prolongation in the duration of the nerve evoked compound action potential (CAP) by nearly 1200% within 300 min while amplitude remained constant for over 20 h. This oxaliplatin effect was almost completely reversed by the gap junction (GJ) inhibitor octanol in a concentration-dependent manner. Further GJ blockers showed similar effects although with a narrower therapeutic window. To clarify the target molecule we studied sciatic nerves from connexin32 (Cx32) and Cx29 knockout (KO) mice. The oxaliplatin effect and neuroprotection by octanol partially persisted in Cx29 better than in Cx32 KO nerves, suggesting that oxaliplatin affects both, but Cx32 GJ channels more than Cx29 hemichannels. Oxaliplatin also accelerated neurobiotin uptake in HeLa cells expressing the human ortholog of Cx29, Cx31.3, as well as dye transfer between cells expressing the human Cx32, and this effect was blocked by octanol. Oxaliplatin caused no morphological changes initially (up to 3 h of exposure), but prolonged nerve exposure caused juxtaparonodal axonal edema, which was prevented by octanol. Our study indicates that oxaliplatin causes forced opening of Cx32 channels and Cx29 hemichannels in peripheral myelinated fibers leading to disruption of axonal K(+) homeostasis. The GJ blocker octanol prevents OIN at very low concentrations and should be further studied as a neuroprotectant. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of olfactory training on the odor threshold in patients with traumatic anosmia.

PubMed

Jiang, Rong-San; Twu, Chih-Wen; Liang, Kai-Li

2017-09-01

Olfactory training is a novel intervention that has been used to treat olfactory dysfunction. This study attempted to investigate the effect of olfactory training in patients with traumatic anosmia. Patients with a clear history of anosmia after experiencing a head injury and whose phenyl ethyl alcohol (PEA) odor detection thresholds were -1 after steroid and zinc treatment were included. The patients were randomly divided into two groups, with patients in one group given a bottle of PEA and those in another group given a bottle of mineral oil for 3-month olfactory training. All the patients were followed up with a PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Magnetic resonance imaging was performed to measure the volume of the olfactory bulbs. Any patient whose PEA threshold result was below -1.01 or whose UPSIT-TC score increased four or more points was considered to have shown improvement in their olfactory function. Forty-two patients received PEA olfactory training, whereas 39 received olfactory training with mineral oil. The improvement of PEA thresholds function was observed in 10 patients within the PEA group and in 2 patients in the mineral oil group. The frequency of improvement of threshold within the PEA group was significantly higher than that of the mineral oil group. Neither olfactory bulb volume nor UPSIT-TC score was significantly different between the two groups. Our results showed that olfactory training with PEA can improve PEA odor threshold levels in patients with traumatic anosmia.

Effect of Atomic Charges on Octanol-Water Partition Coefficient Using Alchemical Free Energy Calculation.

PubMed

Ogata, Koji; Hatakeyama, Makoto; Nakamura, Shinichiro

2018-02-15

The octanol-water partition coefficient (log P ow ) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the log P ow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. However, they must be recalculated for each solvent. Therefore, three different sets of atomic charges were tested using quantum chemical calculations, taking into account vacuum, octanol, and water environments. The calculated atomic charges in the different environments do not necessarily influence the correlation between calculated and experimentally measured ∆ G water values. The largest correlation coefficient values of the solvation free energy in water and octanol were 0.93 and 0.90, respectively. On the other hand, the correlation coefficient of log P ow values calculated from free energies, the largest of which was 0.92, was sensitive to the combination of the solvation free energies calculated from the calculated atomic charges. These results reveal that the solvent assumed in the atomic charge calculation is an important factor determining the accuracy of predicted log P ow values.

Effectiveness of water-air and octanol-air partition coefficients to predict lipophilic flavor release behavior from O/W emulsions.

PubMed

Tamaru, Shunji; Igura, Noriyuki; Shimoda, Mitsuya

2018-01-15

Flavor release from food matrices depends on the partition of volatile flavor compounds between the food matrix and the vapor phase. Thus, we herein investigated the relationship between released flavor concentrations and three different partition coefficients, namely octanol-water, octanol-air, and water-air, which represented the oil, water, and air phases present in emulsions. Limonene, 2-methylpyrazine, nonanal, benzaldehyde, ethyl benzoate, α-terpineol, benzyl alcohol, and octanoic acid were employed. The released concentrations of these flavor compounds from oil-in-water (O/W) emulsions were measured under equilibrium using static headspace gas chromatography. The results indicated that water-air and octanol-air partition coefficients correlated with the logarithms of the released concentrations in the headspace for highly lipophilic flavor compounds. Moreover, the same tendency was observed over various oil volume ratios in the emulsions. Our findings therefore suggest that octanol-air and water-air partition coefficients can be used to predict the released concentration of lipophilic flavor compounds from O/W emulsions. Copyright © 2017 Elsevier Ltd. All rights reserved.

An olfactory demography of a diverse metropolitan population.

PubMed

Keller, Andreas; Hempstead, Margaret; Gomez, Iran A; Gilbert, Avery N; Vosshall, Leslie B

2012-10-10

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. 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. 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 prior experiences with these odours between demographic groups.

Clinical features of olfactory disorders in patients seeking medical consultation

PubMed Central

Chen, Guowei; Wei, Yongxiang; Miao, Xutao; Li, Kunyan; Ren, Yuanyuan; Liu, Jia

2013-01-01

Background Olfactory disorders are common complaints in ENT clinics. We investigated causes and relevant features of olfactory disorders and the need for gustatory testing in patients with olfactory dysfunction. Material/Methods A total of 140 patients seeking medical consultations were enrolled. All patients were asked about their olfactory disorders in a structured interview of medical history and underwent thorough otolaryngologic examinations and imaging of the head. Results Causes of olfactory disorders were classified as: upper respiratory tract infection (URTI), sinonasal diseases (NSD), head trauma, idiopathic, endoscopic sinus surgery, congenital anosmia, and other causes. Each of the various causes of olfactory dysfunction had its own distinct clinical features. Nineteen of 54 patients whose gustation was assessed had gustatory disorders. Conclusions The leading causes of olfactory dysfunction were URTI, NSD, head trauma, and idiopathic causes. Gustatory disorders were fairly common in patients with olfactory dysfunction. High priority should be given to complaints of olfactory disorders. PMID:23748259

Olfactory receptor antagonism between odorants

PubMed Central

Oka, Yuki; Omura, Masayo; Kataoka, Hiroshi; Touhara, Kazushige

2004-01-01

The detection of thousands of volatile odorants is mediated by several hundreds of different G protein-coupled olfactory receptors (ORs). The main strategy in encoding odorant identities is a combinatorial receptor code scheme in that different odorants are recognized by different sets of ORs. Despite increasing information on agonist–OR combinations, little is known about the antagonism of ORs in the mammalian olfactory system. Here we show that odorants inhibit odorant responses of OR(s), evidence of antagonism between odorants at the receptor level. The antagonism was demonstrated in a heterologous OR-expression system and in single olfactory neurons that expressed a given OR, and was also visualized at the level of the olfactory epithelium. Dual functions of odorants as an agonist and an antagonist to ORs indicate a new aspect in the receptor code determination for odorant mixtures that often give rise to novel perceptual qualities that are not present in each component. The current study also provides insight into strategies to modulate perceived odorant quality. PMID:14685265

Drosophila Learn Opposing Components of a Compound Food Stimulus

PubMed Central

Das, Gaurav; Klappenbach, Martín; Vrontou, Eleftheria; Perisse, Emmanuel; Clark, Christopher M.; Burke, Christopher J.; Waddell, Scott

2014-01-01

Summary Dopaminergic neurons provide value signals in mammals and insects [1–3]. During Drosophila olfactory learning, distinct subsets of dopaminergic neurons appear to assign either positive or negative value to odor representations in mushroom body neurons [4–9]. However, it is not known how flies evaluate substances that have mixed valence. Here we show that flies form short-lived aversive olfactory memories when trained with odors and sugars that are contaminated with the common insect repellent DEET. This DEET-aversive learning required the MB-MP1 dopaminergic neurons that are also required for shock learning [7]. Moreover, differential conditioning with DEET versus shock suggests that formation of these distinct aversive olfactory memories relies on a common negatively reinforcing dopaminergic mechanism. Surprisingly, as time passed after training, the behavior of DEET-sugar-trained flies reversed from conditioned odor avoidance into odor approach. In addition, flies that were compromised for reward learning exhibited a more robust and longer-lived aversive-DEET memory. These data demonstrate that flies independently process the DEET and sugar components to form parallel aversive and appetitive olfactory memories, with distinct kinetics, that compete to guide learned behavior. PMID:25042590

β1-Adrenoceptor in the Central Amygdala Is Required for Unconditioned Stimulus-Induced Drug Memory Reconsolidation

PubMed Central

Zhu, Huiwen; Zhou, Yiming; Liu, Zhiyuan; Chen, Xi; Li, Yanqing; Liu, Xing; Ma, Lan

2018-01-01

Abstract Background Drug memories become labile and reconsolidated after retrieval by presentation of environmental cues (conditioned stimulus) or drugs (unconditioned stimulus). Whether conditioned stimulus and unconditioned stimulus retrieval trigger different memory reconsolidation processes is not clear. Methods Protein synthesis inhibitor or β-adrenergic receptor (β-AR) antagonist was systemically administrated or intra-central amygdala infused immediately after cocaine reexposure in cocaine-conditioned place preference or self-administration mice models. β-ARs were selectively knocked out in the central amygdala to further confirm the role of β-adrenergic receptor in cocaine reexposure-induced memory reconsolidation of cocaine-conditioned place preference. Results Cocaine reexposure triggered de novo protein synthesis dependent memory reconsolidation of cocaine-conditioned place preference. Cocaine-priming-induced reinstatement was also impaired with post cocaine retrieval manipulation, in contrast to the relapse behavior with post context retrieval manipulation. Cocaine retrieval, but not context retrieval, induced central amygdala activation. Protein synthesis inhibitor or β1-adrenergic receptor antagonist infused in the central amygdala after cocaine retrieval, but not context retrieval, inhibited memory reconsolidation and reinstatement. β1-adrenergic receptor knockout in the central amygdala suppressed cocaine retrieval-triggered memory reconsolidation and reinstatement of cocaine conditioned place preference. β1-adrenergic receptor antagonism after cocaine retrieval also impaired reconsolidation and reinstatement of cocaine self-administration. Conclusions Cocaine reward memory triggered by unconditioned stimulus retrieval is distinct from conditioned stimulus retrieval. Unconditioned stimulus retrieval induced reconsolidation of cocaine reward memory depends on β1-adrenergic signaling in the central amygdala. Post unconditioned stimulus

High hunger state increases olfactory sensitivity to neutral but not food odors.

PubMed

Stafford, Lorenzo D; Welbeck, Kimberley

2011-01-01

Understanding how hunger state relates to olfactory sensitivity has become more urgent due to their possible role in obesity. In 2 studies (within-subjects: n = 24, between-subjects: n = 40), participants were provided with lunch before (satiated state) or after (nonsatiated state) testing and completed a standardized olfactory threshold test to a neutral odor (Experiments 1 and 2) and discrimination test to a food odor (Experiment 2). Experiment 1 revealed that olfactory sensitivity was greater in the nonsatiated versus satiated state, with additionally increased sensitivity for the low body mass index (BMI) compared with high BMI group. Experiment 2 replicated this effect for neutral odors, but in the case of food odors, those in a satiated state had greater acuity. Additionally, whereas the high BMI group had higher acuity to food odors in the satiated versus nonsatiated state, no such differences were found for the low BMI group. The research here is the first to demonstrate how olfactory acuity changes as a function of hunger state and relatedness of odor to food and that BMI can predict differences in olfactory sensitivity.

Correlation between octanol/water and liposome/water distribution coefficients and drug absorption of a set of pharmacologically active compounds.

PubMed

Esteves, Freddy; Moutinho, Carla; Matos, Carla

2013-06-01

Absorption and consequent therapeutic action are key issues in the development of new drugs by the pharmaceutical industry. In this sense, different models can be used to simulate biological membranes to predict the absorption of a drug. This work compared the octanol/water and the liposome/water models. The parameters used to relate the two models were the distribution coefficients between liposomes and water and octanol and water and the fraction of drug orally absorbed. For this study, 66 drugs were collected from literature sources and divided into four groups according to charge and ionization degree: neutral; positively charged; negatively charged; and partially ionized/zwitterionic. The results show a satisfactory linear correlation between the octanol and liposome systems for the neutral (R²= 0.9324) and partially ionized compounds (R²= 0.9367), contrary to the positive (R²= 0.4684) and negatively charged compounds (R²= 0.1487). In the case of neutral drugs, results were similar in both models because of the high fraction orally absorbed. However, for the charged drugs (positively, negatively, and partially ionized/zwitterionic), the liposomal model has a more-appropriate correlation with absorption than the octanol model. These results show that the neutral compounds only interact with membranes through hydrophobic bonds, whereas charged drugs favor electrostatic interactions established with the liposomes. With this work, we concluded that liposomes may be a more-appropriate biomembrane model than octanol for charged compounds.

Stimulus Variables and Interpersonal Attraction: The Stimulus Context.

ERIC Educational Resources Information Center

Griffitt, William

In interpersonal attraction, studies and judgment research evaluation of a stimulus is often a function of the context within which the stimulus appears. The first experiment was designed to examine "contrast effects" (shifts in the rated value of a stimulus away from the contextual values) when all attitudinal information was received from two…

Mixture and odorant processing in the olfactory systems of insects: a comparative perspective.

PubMed

Clifford, Marie R; Riffell, Jeffrey A

2013-11-01

Natural olfactory stimuli are often complex mixtures of volatiles, of which the identities and ratios of constituents are important for odor-mediated behaviors. Despite this importance, the mechanism by which the olfactory system processes this complex information remains an area of active study. In this review, we describe recent progress in how odorants and mixtures are processed in the brain of insects. We use a comparative approach toward contrasting olfactory coding and the behavioral efficacy of mixtures in different insect species, and organize these topics around four sections: (1) Examples of the behavioral efficacy of odor mixtures and the olfactory environment; (2) mixture processing in the periphery; (3) mixture coding in the antennal lobe; and (4) evolutionary implications and adaptations for olfactory processing. We also include pertinent background information about the processing of individual odorants and comparative differences in wiring and anatomy, as these topics have been richly investigated and inform the processing of mixtures in the insect olfactory system. Finally, we describe exciting studies that have begun to elucidate the role of the processing of complex olfactory information in evolution and speciation.

Influence of amino acid residues near the active site of cytochrome P450 from Bacillus megaterium on the selectivity of n-octane oxidation to octanol regioisomers

NASA Astrophysics Data System (ADS)

Miyaji, Akimitsu; Baba, Toshihide

2017-09-01

A mutant of cytochrome P450 from Bacillus megaterium (CYP450BM-3) was prepared by replacing two alanine residues around active site of the enzyme, alanine 328 and alanine 82, with leucine and tryptophan, respectively. The CYP450BM-3 mutant produced 2-octanol selectively from n-octane under atmospheric temperature and pressure; its selectivity was 74%. Furthermore, the mutant produced 1-octanol, which is not produced by wild-type enzyme.

Carving Executive Control at Its Joints: Working Memory Capacity Predicts Stimulus-Stimulus, but Not Stimulus-Response, Conflict

ERIC Educational Resources Information Center

Meier, Matt E.; Kane, Michael J.

2015-01-01

Three experiments examined the relation between working memory capacity (WMC) and 2 different forms of cognitive conflict: stimulus-stimulus (S-S) and stimulus-response (S-R) interference. Our goal was to test whether WMC's relation to conflict-task performance is mediated by stimulus-identification processes (captured by S-S conflict),…

Quantum Dot Distribution in the Olfactory Epithelium After Nasal Delivery

NASA Astrophysics Data System (ADS)

Garzotto, D.; De Marchis, S.

2010-10-01

Nanoparticles are used in a wide range of human applications from industrial to bio-medical fields. However, the unique characteristics of nanoparticles, such as the small size, large surface area per mass and high reactivity raises great concern on the adverse effects of these particles on ecological systems and human health. There are several pioneer studies reporting translocation of inhaled particulates to the brain through a potential neuronal uptake mediated by the olfactory nerve (1, 2, 3). However, no direct evidences have been presented up to now on the pathway followed by the nanoparticles from the nose to the brain. In addition to a neuronal pathway, nanoparticles could gain access to the central nervous system through extracellular pathways (perineuronal, perivascular and cerebrospinal fluid paths). In the present study we investigate the localization of intranasally delivered fluorescent nanoparticles in the olfactory epithelium. To this purpose we used quantum dots (QDs), a model of innovative fluorescent semiconductor nanocrystals commonly used in cell and animal biology (4). Intranasal treatments with QDs were performed acutely on adult CD1 mice. The olfactory epithelium was collected and analysed by confocal microscopy at different survival time after treatment. Data obtained indicate that the neuronal components of the olfactory epithelium are not preferentially involved in QDs uptake, thus suggesting nanoparticles can cross the olfactory epithelium through extracellular pathways.

Cladistic Analysis of Olfactory and Vomeronasal Systems

PubMed Central

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

Cladistic analysis of olfactory and vomeronasal systems.

PubMed

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

2011-01-01

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.

Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

PubMed Central

Chery, Romain; L'Heureux, Barbara; Bendahmane, Mounir; Renaud, Rémi; Martin, Claire; Pain, Frédéric; Gurden, Hirac

2011-01-01

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4. The olfactory system is of central importance for the survival of the vast majority of living species because it

Dock and Pak regulate olfactory axon pathfinding in Drosophila.

PubMed

Ang, Lay-Hong; Kim, Jenny; Stepensky, Vitaly; Hing, Huey

2003-04-01

The convergence of olfactory axons expressing particular odorant receptor (Or) genes on spatially invariant glomeruli in the brain is one of the most dramatic examples of precise axon targeting in developmental neurobiology. The cellular and molecular mechanisms by which olfactory axons pathfind to their targets are poorly understood. We report here that the SH2/SH3 adapter Dock and the serine/threonine kinase Pak are necessary for the precise guidance of olfactory axons. Using antibody localization, mosaic analyses and cell-type specific rescue, we observed that Dock and Pak are expressed in olfactory axons and function autonomously in olfactory neurons to regulate the precise wiring of the olfactory map. Detailed analyses of the mutant phenotypes in whole mutants and in small multicellular clones indicate that Dock and Pak do not control olfactory neuron (ON) differentiation, but specifically regulate multiple aspects of axon trajectories to guide them to their cognate glomeruli. Structure/function studies show that Dock and Pak form a signaling pathway that mediates the response of olfactory axons to guidance cues in the developing antennal lobe (AL). Our findings therefore identify a central signaling module that is used by ONs to project to their cognate glomeruli.

Early Stage olfactory neuroblastoma and the impact of resecting dura and olfactory bulb.

PubMed

Mays, Ashley C; Bell, Diana; Ferrarotto, Renata; Phan, Jack; Roberts, Dianna; Fuller, Clifton D; Frank, Steven J; Raza, Shaan M; Kupferman, Michael E; DeMonte, Franco; Hanna, Ehab Y; Su, Shirley Y

2018-06-01

Compare outcomes of patients with olfactory neuroblastoma (ONB) without skull base involvement treated with and without resection of the dura and olfactory bulb. Retrospective review of ONB patients treated from 1992 to 2013 at the MD Anderson Cancer Center (The University of Texas, Houston, Texas, U.S.A.). Primary outcomes were overall and disease-free survival. Thirty-five patients were identified. Most patients had Kadish A/B. tumors (97%), Hyams grade 2 (70%), with unilateral involvement (91%), and arising from the nasal cavity (68%). Tumor involved the mucosa abutting the skull base in 42% of patients. Twenty-five patients (71%) received surgery and radiation, whereas the remainder had surgery alone. Five patients (14%) had bony skull base resection, and eight patients (23%) had resection of bony skull base, dura, and olfactory bulb. Surgical margins were grossly positive in one patient (3%) and microscopically positive in four patients (12%). The 5- and 10-year overall survival were 93% and 81%, respectively. The 5- and 10-year disease-free survival (DFS) were 89% and 78%, respectively. Bony cribriform plate resection was associated with better DFS (P = 0.05), but dura and olfactory bulb resection was not (P = 0.11). There was a trend toward improved DFS in patients with negative resection margins (P = 0.19). Surgical modality (open vs. endoscopic) and postoperative radiotherapy did not impact DFS. Most Kadish A/B ONB tumors have low Hyams grade, unilateral involvement, and favorable survival outcomes. Resection of the dura and olfactory bulb is not oncologically advantageous in patients without skull base involvement who are surgically treated with negative resection margins and cribriform resection. 4. Laryngoscope, 128:1274-1280, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

A circadian clock in the olfactory bulb anticipates feeding during food anticipatory activity.

PubMed

Nolasco, Nahum; Juárez, Claudia; Morgado, Elvira; Meza, Enrique; Caba, Mario

2012-01-01

Rabbit pups ingest food, in this case milk, once a day with circadian periodicity and are a natural model of food anticipatory activity. During nursing, several sensory systems receive information about properties of the food, one of them being the olfactory system, which has received little attention in relation to synchronization by food. In addition, the olfactory bulb has a circadian pacemaker that exhibits rhythms independently of the suprachiasmatic nucleus, but the biological functions of these rhythms are largely unknown. In the present contribution, we hypothesized that circadian suckling of milk synchronizes rhythms in the olfactory bulb. To this aim we explored by immunohistochemistry, rhythms of FOS and PER1 proteins, as indicators of activation and reporter of oscillations, respectively, through a complete 24-h cycle in periglomerular, mitral and granular cell layers of both the main and the accessory olfactory bulb. Subjects were 7-day-old rabbit pups scheduled to nurse during the night (02:00 h) or day (10:00 h), and also fasted subjects, to explore the possible persistence of oscillations. In the three layers of the main olfactory bulb, FOS was high at time of nursing, then further increased 1.5 h afterward, and then decreased to increase again in advance of the next nursing bout. This pattern persisted, without the postprandial increase, in fasted subjects with a shift in subjects nursed at 02:00. PER1 was increased 2-8 h after nursing and this increase persisted in most cell layers, with a shift, in fasted subjects. In the accessory olfactory bulb we only observed a consistent pattern of FOS expression in the mitral cell layer of nursed subjects, similar to that of the main olfactory bulb. We conclude that the main olfactory bulb is synchronized during milk ingestion, but during fasting its oscillations perhaps are modulated by the suprachiasmatic nucleus, as proposed for rodents.

Comparison of prediction methods for octanol-air partition coefficients of diverse organic compounds.

PubMed

Fu, Zhiqiang; Chen, Jingwen; Li, Xuehua; Wang, Ya'nan; Yu, Haiying

2016-04-01

The octanol-air partition coefficient (KOA) is needed for assessing multimedia transport and bioaccumulability of organic chemicals in the environment. As experimental determination of KOA for various chemicals is costly and laborious, development of KOA estimation methods is necessary. We investigated three methods for KOA prediction, conventional quantitative structure-activity relationship (QSAR) models based on molecular structural descriptors, group contribution models based on atom-centered fragments, and a novel model that predicts KOA via solvation free energy from air to octanol phase (ΔGO(0)), with a collection of 939 experimental KOA values for 379 compounds at different temperatures (263.15-323.15 K) as validation or training sets. The developed models were evaluated with the OECD guidelines on QSAR models validation and applicability domain (AD) description. Results showed that although the ΔGO(0) model is theoretically sound and has a broad AD, the prediction accuracy of the model is the poorest. The QSAR models perform better than the group contribution models, and have similar predictability and accuracy with the conventional method that estimates KOA from the octanol-water partition coefficient and Henry's law constant. One QSAR model, which can predict KOA at different temperatures, was recommended for application as to assess the long-range transport potential of chemicals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

Hunger state affects both olfactory abilities and gustatory sensitivity.

PubMed

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 < 0.001). The comparison of gustatory sensitivity indicated significantly higher sensitivity to sweet, sour and salty in hunger (p < 0.001), but significantly higher sensitivity to bitter tastant in satiety (p < 0.001). With this prospective study, we were able to show that both olfactory abilities and gustatory sensitivity were affected by hunger state.

Determination of octanol-air partition coefficients and supercooled liquid vapor pressures of PAHs as a function of temperature: Application to gas-particle partitioning in an urban atmosphere

NASA Astrophysics Data System (ADS)

Odabasi, Mustafa; Cetin, Eylem; Sofuoglu, Aysun

Octanol-air partition coefficients ( KOA) for 14 polycyclic aromatic hydrocarbons (PAHs) were determined as a function of temperature using the gas chromatographic retention time method. log KOA values at 25° ranged over six orders of magnitude, between 6.34 (acenaphthylene) and 12.59 (dibenz[ a,h]anthracene). The determined KOA values were within factor of 0.7 (dibenz[ a,h]anthracene) to 15.1 (benz[ a]anthracene) of values calculated as the ratio of octanol-water partition coefficient to dimensionless Henry's law constant. Supercooled liquid vapor pressures ( PL) of 13 PAHs were also determined using the gas chromatographic retention time technique. Activity coefficients in octanol calculated using KOA and PL ranged between 3.2 and 6.2 indicating near-ideal solution behavior. Atmospheric concentrations measured in this study in Izmir, Turkey were used to investigate the partitioning of PAHs between particle and gas-phases. Experimental gas-particle partition coefficients ( Kp) were compared to the predictions of KOA absorption and KSA (soot-air partition coefficient) models. Octanol-based absorptive partitioning model predicted lower partition coefficients especially for relatively volatile PAHs. Ratios of measured/modeled partition coefficients ranged between 1.1 and 15.5 (4.5±6.0, average±SD) for KOA model. KSA model predictions were relatively better and measured to modeled ratios ranged between 0.6 and 5.6 (2.3±2.7, average±SD).

Testicular receptor 2, Nr2c1, is associated with stem cells in the developing olfactory epithelium and other cranial sensory and skeletal structures.

PubMed

Baker, Jennifer L; Wood, Bernard; Karpinski, Beverly A; LaMantia, Anthony-S; Maynard, Thomas M

2016-01-01

Comparative genomic analysis of the nuclear receptor family suggests that the testicular receptor 2, Nr2c1, undergoes positive selection in the human-chimpanzee clade based upon a significant increase in nonsynonymous compared to synonymous substitutions. Previous in situ analyses of Nr2c1 lacked the temporal range and spatial resolution necessary to characterize cellular expression of this gene from early to mid gestation, when many nuclear receptors are key regulators of tissue specific stem or progenitor cells. Thus, we asked whether Nr2c1 protein is associated with stem cell populations in the mid-gestation mouse embryo. Nr2c1 is robustly expressed in the developing olfactory epithelium. Its expression in the olfactory epithelium shifts from multiple progenitor classes at early stages to primarily transit amplifying cells later in olfactory epithelium development. In the early developing central nervous system, Nr2c1 is limited to the anterior telencephalon/olfactory bulb anlagen, coincident with Nestin-positive neuroepithelial stem cells. Nr2c1 is also seen in additional cranial sensory specializations including cells surrounding the mystacial vibrissae, the retinal pigment epithelium and Scarpa's ganglion. Nr2c1 was also detected in a subset of mesenchymal cells in developing teeth and cranial bones. The timing and distribution of embryonic expression suggests that Nr2c1 is primarily associated with the early genesis of mammalian cranial sensory neurons and craniofacial skeletal structures. Thus, Nr2c1 may be a candidate for mediating parallel adaptive changes in cranial neural sensory specializations such as the olfactory epithelium, retina and mystacial vibrissae and in non-neural craniofacial features including teeth. Copyright © 2015 Elsevier B.V. All rights reserved.

An olfactory demography of a diverse metropolitan population

PubMed Central

2012-01-01

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 prior experiences with these

The role of social relationships in the link between olfactory dysfunction and mortality.

PubMed

Leschak, Carrianne J; Eisenberger, Naomi I

2018-01-01

Recent work suggests that olfactory dysfunction is a strong predictor of five-year mortality in older adults. Based on past work showing: 1) that olfactory dysfunction impairs social functioning and 2) that social ties are linked with mortality, the current work explored whether impairments in social life mediated the relationship between olfactory dysfunction and mortality. Additionally, based on work showing gender differences in the social consequences of olfactory dysfunction, gender was assessed as a potential moderator of this association. Social network size mediated the olfactory-mortality link for females. To probe what feature of social networks was driving this effect, we investigated two subcomponents of social life: emotional closeness (e.g., perceived social support, loneliness) and physical closeness (e.g., physical contact, in-person socializing with others). Physical closeness significantly mediated the olfactory-mortality link for females, even after controlling for social network size. Emotional closeness did not mediate this link. Possible mechanisms underlying this relationship are discussed.

Odour discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

PubMed

Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2018-06-15

Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odour. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat, Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odour (PO) and aversive odour (AO) memory in C. sphinx We used preferred (0.8% w/w cinnamon powder) and aversive (0.4% w/v citral) odour substances, with freshly prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of EGR-1 and c-Fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but was different for AO. The response to AO elevated the level of c-Fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism involving protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that C-fos expression is possibly controlled by odour-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

Discriminative stimulus effects of inhaled1,1,1-trichloroethane in mice: comparison to other hydrocarbon vapors and volatile anesthetics

PubMed Central

Shelton, Keith L.

2009-01-01

Rationale Because the toxicity of many inhalants precludes evaluation in humans, drug discrimination, an animal model of subjective effects, can be used to gain insights on their poorly understood abuse-related effects. Objectives The purpose of the present study was to train a prototypic inhalant that has known abuse liability, 1,1,1-trichloroethane (TCE), as a discriminative stimulus in mice and compare it to other classes of inhalants. Methods Eight B6SJLF1/J mice were trained to discriminate 10 min of exposure to 12000 ppm inhaled TCE vapor from air and seven mice were trained to discriminate 4000 ppm TCE from air. Tests were then conducted to characterize the discriminative stimulus of TCE and to compare it to representative aromatic and chlorinated hydrocarbon vapors, volatile halogenated anesthetics as well as an odorant compound. Results Only the 12000 ppm TCE versus air discrimination group exhibited sufficient discrimination accuracy for substitution testing. TCE vapor concentration- and exposure time-dependently substituted for the 12000 ppm TCE vapor training stimulus. Full substitution was produced by trichloroethylene, toluene, enflurane and sevoflurane. Varying degrees of partial substitution were produced by the other volatile test compounds. The odorant, 2-butanol, did not produce any substitution for TCE. Conclusions The discriminative stimulus effects of TCE are shared fully or partially by chlorinated and aromatic hydrocarbons as well as by halogenated volatile anesthetics. However, these compounds can be differentiated from TCE both quantitatively and qualitatively. It appears that the degree of similarity is not solely a function of chemical classification but may also be dependent upon the neurochemical effects of the individual compounds. PMID:18972104

Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

PubMed Central

Turetsky, Bruce I.; Hahn, Chang-Gyu; Borgmann-Winter, Karin; Moberg, Paul J.

2009-01-01

Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that underlie disease-related cognitive and emotional disturbances. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indicator of schizophrenia pathology and may even serve as an “early warning” sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Convergent data indicate that structural and functional abnormalities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypothesis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers. PMID:19793796

Immobilized Candida antarctica lipase B on ZnO nanowires/macroporous silica composites for catalyzing chiral resolution of (R,S)-2-octanol.

PubMed

Shang, Chuan-Yang; Li, Wei-Xun; Zhang, Rui-Feng

2014-01-01

ZnO nanowires were successfully introduced into a macroporous SiO2 by in situ hydrothermal growth in 3D pores. The obtained composites were characterized by SEM and XRD, and used as supports to immobilize Candida antarctica lipase B (CALB) through adsorption. The high specific surface area (233 m(2)/g) and strong electrostatic interaction resulted that the average loading amount of the composite supports (196.8 mg/g) was 3-4 times of that of macroporous SiO2 and approximate to that of a silica-based mesoporous material. Both adsorption capacity and the activity of the CALB immobilized on the composite supports almost kept unchanged as the samples were soaked in buffer solution for 48 h. The chiral resolution of 2-octanol was catalyzed by immobilized CALB. A maximum molar conversion of 49.1% was achieved with 99% enantiomeric excess of (R)-2-octanol acetate under the optimal condition: a reaction using 1.0 mol/L (R,S)-2-octanol, 2.0 mol/L vinyl acetate and 4.0 wt.% water content at 60°C for 8h. After fifteen recycles the immobilized lipase could retain 96.9% of relative activity and 93.8% of relative enantioselectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of Olfactory Function in MAPT-Associated Neurodegenerative Disease Reveals Odor-Identification Irreproducibility as a Non-Disease-Specific, General Characteristic of Olfactory Dysfunction.

PubMed

Markopoulou, Katerina; Chase, Bruce A; Robowski, Piotr; Strongosky, Audrey; Narożańska, Ewa; Sitek, Emilia J; Berdynski, Mariusz; Barcikowska, Maria; Baker, Matt C; Rademakers, Rosa; Sławek, Jarosław; Klein, Christine; Hückelheim, Katja; Kasten, Meike; Wszolek, Zbigniew K

2016-01-01

Olfactory dysfunction is associated with normal aging, multiple neurodegenerative disorders, including Parkinson's disease, Lewy body disease and Alzheimer's disease, and other diseases such as diabetes, sleep apnea and the autoimmune disease myasthenia gravis. The wide spectrum of neurodegenerative disorders associated with olfactory dysfunction suggests different, potentially overlapping, underlying pathophysiologies. Studying olfactory dysfunction in presymptomatic carriers of mutations known to cause familial parkinsonism provides unique opportunities to understand the role of genetic factors, delineate the salient characteristics of the onset of olfactory dysfunction, and understand when it starts relative to motor and cognitive symptoms. We evaluated olfactory dysfunction in 28 carriers of two MAPT mutations (p.N279K, p.P301L), which cause frontotemporal dementia with parkinsonism, using the University of Pennsylvania Smell Identification Test. Olfactory dysfunction in carriers does not appear to be allele specific, but is strongly age-dependent and precedes symptomatic onset. Severe olfactory dysfunction, however, is not a fully penetrant trait at the time of symptom onset. Principal component analysis revealed that olfactory dysfunction is not odor-class specific, even though individual odor responses cluster kindred members according to genetic and disease status. Strikingly, carriers with incipient olfactory dysfunction show poor inter-test consistency among the sets of odors identified incorrectly in successive replicate tests, even before severe olfactory dysfunction appears. Furthermore, when 78 individuals without neurodegenerative disease and 14 individuals with sporadic Parkinson's disease were evaluated twice at a one-year interval using the Brief Smell Identification Test, the majority also showed inconsistency in the sets of odors they identified incorrectly, independent of age and cognitive status. While these findings may reflect the

Structural and dipolar properties of the voltage-dependent pore former alamethicin in octanol/dioxane.

PubMed Central

Schwarz, G; Savko, P

1982-01-01

Dielectric constant and loss of the membrane-active peptide alamethicin in octanol/dioxane mixtures have been measured at frequencies between 5 kHz and 50 MHz. On the basis of a rotational mechanism of dipolar orientation, the observed dispersion provides information regarding size, shape, and dipole moment of the structural entities which the solute may assume in media of diverse lipophilicity. Particularly detailed results are obtained in a pure octanol solvent where an apparent molecular weight of alamethicin could be determined. It turns out that in this quite lipophilic medium most of the peptide material exists as a monomer particle that has approximate length and diameter of 35 and 13 A, respectively. It carries a dipole moment of approximately 75 Debye units (directed nearly parallel to the long axis). At our concentrations of a few milligrams per milliliters, appreciable formation of dimers by head-to-tail linkage is indicated. When the octanol content is reduced by adding greater amounts of dioxane, larger particles are encountered. This is accompanied by a decrease of the effective polarity. The inherent increase of hydrophilicity in the dioxane-enriched solvent apparently favors another monomer conformation that has a low dipole moment and easily aggregates to some kind of micelle. PMID:7115881

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

PubMed

Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Fluctuating olfactory sensitivity and distorted odor perception in allergic rhinitis.

PubMed

Apter, A J; Gent, J F; Frank, M E

1999-09-01

To characterize the relationship between allergic rhinitis, the severity and duration of nasal disease, olfactory function, and self-reported olfactory symptoms, including fluctuations or distortions in odor perception. Assessment of olfactory function and symptoms of 90 patients with allergic rhinitis. A clinic of a university teaching hospital and research facility. Sixty patients who presented to the Taste and Smell Clinic who had positive allergy test results and 30 patients who presented to the Allergy-Immunology Clinic. The Taste and Smell Clinic patients were grouped by nasal-sinus disease status (30 without chronic rhinosinusitis or nasal polyps, 14 with chronic rhinosinusitis but without polyps, and 16 with nasal polyps). Subjective olfactory symptom questionnaire and objective olfactory function tests. The Allergy-Immunology Clinic patients were diagnosed as being normosmic and the Taste and Smell Clinic patients as being hyposmic or anosmic with olfactory loss that increased significantly with nasal-sinus disease severity. Comparisons with normative data confirm that olfactory scores observed in all groups were significantly lower than expected because of the aging process alone. The self-reported duration of olfactory loss increased significantly with nasal-sinus disease severity. The Taste and Smell Clinic patients without chronic rhinosinusitis or nasal polyps reported the greatest incidence of olfactory distortions and olfactory loss associated with upper respiratory tract infections. There appears to be a continuum of duration and severity of olfactory loss in allergic rhinitis that parallels increasing severity of nasal-sinus disease. As a result of the increased frequency of respiratory infection associated with allergic rhinitis, these patients are at risk for damage to the olfactory epithelium.

Methods to measure olfactory behavior in mice

PubMed Central

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

2015-01-01

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’s olfactory function, including olfactory habituation, discrimination, odor preference, odor detection sensitivity, and olfactory memory, to both social and nonsocial odors. PMID:25645244

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-01-01

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962

Olfactory discrimination predicts cognitive decline among community-dwelling older adults.

PubMed

Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N

2012-05-22

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.

Ion-specific weak adsorption of salts and water/octanol transfer free energy of a model amphiphilic hexapeptide.

PubMed

Déjugnat, Christophe; Dufrêche, Jean-François; Zemb, Thomas

2011-04-21

An amphiphilic hexapeptide has been used as a model to quantify how specific ion effects induced by addition of four salts tune the hydrophilic/hydrophobic balance and induce temperature-dependant coacervate formation from aqueous solution. The hexapeptide chosen is present as a dimer with low transfer energy from water to octanol. Taking sodium chloride as the reference state in the Hofmeister scale, we identify water activity effects and therefore measure the free energy of transfer from water to octanol and separately the free energy associated to the adsorption of chaotropic ions or the desorption of kosmotropic ions for the same amphiphilic peptide. These effects have the same order of magnitude: therefore, both energies of solvation as well as transfer into octanol strongly depend on the nature of the electrolytes used to formulate any buffer. Model peptides could be used on separation processes based on criteria linked to "Hofmeister" but different from volume and valency.

Accurate prediction of personalized olfactory perception from large-scale chemoinformatic features.

PubMed

Li, Hongyang; Panwar, Bharat; Omenn, Gilbert S; Guan, Yuanfang

2018-02-01

The olfactory stimulus-percept problem has been studied for more than a century, yet it is still hard to precisely predict the odor given the large-scale chemoinformatic features of an odorant molecule. A major challenge is that the perceived qualities vary greatly among individuals due to different genetic and cultural backgrounds. Moreover, the combinatorial interactions between multiple odorant receptors and diverse molecules significantly complicate the olfaction prediction. Many attempts have been made to establish structure-odor relationships for intensity and pleasantness, but no models are available to predict the personalized multi-odor attributes of molecules. In this study, we describe our winning algorithm for predicting individual and population perceptual responses to various odorants in the DREAM Olfaction Prediction Challenge. We find that random forest model consisting of multiple decision trees is well suited to this prediction problem, given the large feature spaces and high variability of perceptual ratings among individuals. Integrating both population and individual perceptions into our model effectively reduces the influence of noise and outliers. By analyzing the importance of each chemical feature, we find that a small set of low- and nondegenerative features is sufficient for accurate prediction. Our random forest model successfully predicts personalized odor attributes of structurally diverse molecules. This model together with the top discriminative features has the potential to extend our understanding of olfactory perception mechanisms and provide an alternative for rational odorant design.

Hypothalamus-Olfactory System Crosstalk: Orexin A Immunostaining in Mice

PubMed Central

Gascuel, Jean; Lemoine, Aleth; Rigault, Caroline; Datiche, Frédérique; Benani, Alexandre; Penicaud, Luc; Lopez-Mascaraque, Laura

2012-01-01

It is well known that olfaction influences food intake, and conversely, that an individual’s nutritional status modulates olfactory sensitivity. However, what is still poorly understood is the neuronal correlate of this relationship, as well as the connections between the olfactory bulb and the hypothalamus. The goal of this report is to analyze the relationship between the olfactory bulb and hypothalamus, focusing on orexin A immunostaining, a hypothalamic neuropeptide that is thought to play a role in states of sleep/wakefulness. Interestingly, orexin A has also been described as a food intake stimulator. Such an effect may be due in part to the stimulation of the olfactory bulbar pathway. In rats, orexin positive cells are concentrated strictly in the lateral hypothalamus, while their projections invade nearly the entire brain including the olfactory system. Therefore, orexin appears to be a good candidate to play a pivotal role in connecting olfactory and hypothalamic pathways. So far, orexin has been described in rats, however, there is still a lack of information concerning its expression in the brains of adult and developing mice. In this context, we revisited the orexin A pattern in adult and developing mice using immunohistological methods and confocal microscopy. Besides minor differences, orexin A immunostaining in mice shares many features with those observed in rats. In the olfactory bulb, even though there are few orexin projections, they reach all the different layers of the olfactory bulb. In contrast to the presence of orexin projections in the main olfactory bulb, almost none have been found in the accessory olfactory bulb. The developmental expression of orexin A supports the hypothesis that orexin expression only appears post-natally. PMID:23162437

Preservation of olfaction in surgery of olfactory groove meningiomas.

PubMed

Jang, Woo-Youl; Jung, Shin; Jung, Tae-Young; Moon, Kyung-Sub; Kim, In-Young

2013-08-01

Olfaction is commonly considered as secondary among the sensory functions, perhaps reflecting a lack of interest in sparing olfaction after surgery for the olfactory groove meningiomas (OGM). However, considering the repercussions of olfaction for the quality of life, the assessment of post-operative olfaction should be necessary. We retrospectively reviewed the olfactory outcome in patients with OGM and investigated the factors associated with sparing the post-operative olfaction. Between 1993 and 2012, 40 patients with OGM underwent surgical resection and estimated the olfactory function using the Korean version of "Sniffin'Sticks" test (KVSS). Variable factors, such as tumor size, degree of preoperative edema, tumor consistency, preoperative olfactory function, surgical approaches, patient's age, and gender were analyzed with attention to the post-operative olfactory function. Anatomical and functional preservation of olfactory structures were achieved in 26 patients (65%) and 22 patients (55%), respectively. Among the variable factors, size of tumor was significant related to the preservation of post-operative olfaction. (78.6% in size<4 cm and 42.3% in size>4 cm, p=0.035). Sparing the olfaction was significantly better in patients without preoperative olfactory dysfunction (84.6%) compared with ones with preoperative olfactory dysfunction (40.7%, p=0.016). The frontolateral approach achieved much more excellent post-operative olfactory function (71.4%) than the bifrontal approach (36.8%, p=0.032). If the tumor was smaller than 4 cm and the patients did not present olfactory dysfunction preoperatively, the possibility of sparing the post-operative olfaction was high. Among the variable surgical approaches, frontolateral route may be preferable sparing the post-operative olfaction. Copyright © 2012 Elsevier B.V. All rights reserved.

Early olfactory environment influences social behaviour in adult Octodon degus.

PubMed

Márquez, Natalia; Martínez-Harms, Jaime; Vásquez, Rodrigo A; Mpodozis, Jorge

2015-01-01

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.

Effect of strong fragrance on olfactory detection threshold.

PubMed

Fasunla, Ayotunde James; Douglas, David Dayo; Adeosun, Aderemi Adeleke; Steinbach, Silke; Nwaorgu, Onyekwere George Benjamin

2014-09-01

To assess the olfactory threshold of healthy volunteers at the University College Hospital, Ibadan and to investigate the effect of perfume on their olfactory detection thresholds. A quasi-experimental study on olfactory detection thresholds of healthy volunteers from September 2013 to November 2013. Tertiary health institution. A structured questionniare was administered to the participants in order to obtain information on sociodemographics, occupation, ability to perceive smell, use of perfume, effects of perfume on appetite and self-confidence, history of allergy, and previous nasal surgery. Participants subjectively rated their olfactory performance. Subsequently, they had olfactory detection threshold testing done at baseline and after exposure to perfume with varied concentrations of n-butanol in a forced triple response and staircase fashion. Healthy volunteers, 37 males and 63 females, were evaluated. Their ages ranged from 19 to 59 years with a mean of 31 years ± 8. Subjectively, 94% of the participants had excellent olfactory function. In the pre-exposure forced triple response, 88% were able to detect the odor at ≤.25 mmol/l concentration while in the post-exposure forced triple response, only 66% were able to detect the odor at ≤.25 mmol/l concentration. There is also a statistical significant difference in the olfactory detection threshold score between the pre-exposure and post-exposure period in the participants (P < .05). Use of strong fragrances affects the olfactory detection threshold. Therefore patients and clinicians should be aware of this and its effects on the outcome of test of olfaction. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Spontaneous assembly of HSP90 inhibitors at water/octanol interface: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Zolghadr, Amin Reza; Boroomand, Samaneh

2017-02-01

Drug absorption at an acceptable dose depends on the pair of solubility and permeability. There are many potent therapeutics that are not active in vivo, presumably due to the lack of capability to cross the cell membrane. Molecular dynamics simulation of radicicol, diol-radicicol, cyclopropane-radicicol and 17-DMAG were performed at water/octanol interface to suggest interfacial activity as a physico-chemical characteristic of these heat shock protein 90 (HSP90) inhibitors. We have observed that orally active HSP90 inhibitors form aggregates at the water/octanol and DPPC-lipid/water interfaces by starting from an initial configuration with HSP90 inhibitors embedded in the water matrix.

Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

2013-01-15

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidativemore » stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. �

Risk factors for hazardous events in olfactory-impaired patients.

PubMed

Pence, Taylor S; Reiter, Evan R; DiNardo, Laurence J; Costanzo, Richard M

2014-10-01

Normal olfaction provides essential cues to allow early detection and avoidance of potentially hazardous situations. Thus, patients with impaired olfaction may be at increased risk of experiencing certain hazardous events such as cooking or house fires, delayed detection of gas leaks, and exposure to or ingestion of toxic substances. To identify risk factors and potential trends over time in olfactory-related hazardous events in patients with impaired olfactory function. Retrospective cohort study of 1047 patients presenting to a university smell and taste clinic between 1983 and 2013. A total of 704 patients had both clinical olfactory testing and a hazard interview and were studied. On the basis of olfactory function testing results, patients were categorized as normosmic (n = 161), mildly hyposmic (n = 99), moderately hyposmic (n = 93), severely hyposmic (n = 142), and anosmic (n = 209). Patient evaluation including interview, examination, and olfactory testing. Incidence of specific olfaction-related hazardous events (ie, burning pots and/or pans, starting a fire while cooking, inability to detect gas leaks, inability to detect smoke, and ingestion of toxic substances or spoiled foods) by degree of olfactory impairment. The incidence of having experienced any hazardous event progressively increased with degree of impairment: normosmic (18.0%), mildly hyposmic (22.2%), moderately hyposmic (31.2%), severely hyposmic (32.4%), and anosmic (39.2%). Over 3 decades there was no significant change in the overall incidence of hazardous events. Analysis of demographic data (age, sex, race, smoking status, and etiology) revealed significant differences in the incidence of hazardous events based on age (among 397 patients <65 years, 148 [37.3%] with hazardous event, vs 31 of 146 patients ≥65 years [21.3%]; P < .001), sex (among 278 women, 106 [38.1%] with hazardous event, vs 73 of 265 men [27.6%]; P = .009), and race (among 98 African

[Deficits in medical counseling in olfactory dysfunction].

PubMed

Haxel, B R; Nisius, A; Fruth, K; Mann, W J; Muttray, A

2012-05-01

Olfactory dysfunctions are common with a prevalence of up to 20% in the population. An impaired sense of smell can lead to specific dangers, therefore, counseling and warning of hazardous situations to raise patient awareness is an important medical function. In this study 105 patients presenting to the University of Mainz Medical Centre with dysosmia were evaluated using a questionnaire. For quantification of the olfactory dysfunction a standardized olfactory test (Sniffin' Sticks) was used. Of the patients 46% were hyposmic and 40% were functionally anosmic. The median duration of the olfactory impairment was 10 months and the main causes of dysosmia were upper respiratory tract infections and idiopathic disorders. More than 90% of the patients consulted an otorhinolaryngologist and 60% a general practitioner before presenting to the University of Mainz Medical Center. More than two thirds of the patients conducted a professional activity, 95% of patients reported that they had not received any medical counseling and 6% of the subjects were forced to discontinue their profession because of olfactory dysfunction. In patients with olfactory dysfunctions appropriate diagnostics, including olfactometry should be performed. Furthermore, correct medical counseling concerning necessary additional arrangements (e.g. installation of smoke or gas detectors, precautions while cooking or for hygiene) has to be performed. For patients in a profession an analysis of the hazards at work is crucial.

Determination and prediction of octanol-air partition coefficients of hydroxylated and methoxylated polybrominated diphenyl ethers.

PubMed

Zhao, Hongxia; Xie, Qing; Tan, Feng; Chen, Jingwen; Quan, Xie; Qu, Baocheng; Zhang, Xin; Li, Xiaona

2010-07-01

The octanol-air partition coefficient (K(OA)) of 19 hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and 10 methoxylated polybrominated diphenyl ethers (MeO-PBDEs) were measured as a function of temperature using a gas chromatographic retention time technique. At room temperature (298.15K), log K(OA) ranged from 8.30 for monobrominated OH/MeO-PBDEs to 13.29 for hexabrominated OH/MeO-PBDEs. The internal energies of phase change from octanol to air (Delta(OA)U) for 29 OH/MeO-PBDE congeners ranged from 72 to 126 kJ mol(-1). Using partial least-squares (PLS) analysis, a statistically quantitative structure-property relationship (QSPR) model for logK(OA) of OH/MeO-PBDE congeners was developed based on the 16 fundamental quantum chemical descriptors computed by PM3 Hamiltonian, for which the Q(cum)(2) was about 0.937. The molecular weight (Mw) and energy of the lowest unoccupied molecular orbital (E(LUMO)) were found to be main factors governing the log K(OA). 2010 Elsevier Ltd. All rights reserved.

Orthogonal stimulus-response compatibility effects emerge even when the stimulus position is task irrelevant.

PubMed

Nishimura, Akio; Yokosawa, Kazuhiko

2006-06-01

The above-right/below-left mapping advantage with vertical stimuli and horizontal responses is known as the orthogonal stimulus-response compatibility (SRC) effect. We investigated whether the orthogonal SRC effect emerges with irrelevant stimulus dimensions. In Experiment 1, participants responded with a right or left key press to the colour of the stimulus presented above or below the fixation. We observed an above-right/below-left advantage (orthogonal Simon effect). In Experiment 2, we manipulated the polarity in the response dimension by varying the horizontal location of the response set. The orthogonal Simon effect decreased and even reversed as the left response code became more positive. This result provides evidence for the automatic activation of the positive and negative response codes by the corresponding positive and negative stimulus codes. These findings extended the orthogonal SRC effect based on coding asymmetry to an irrelevant stimulus dimension.

Role of olfactory bulb serotonin in olfactory learning in the greater short-nosed fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae).

PubMed

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.

N2pc is modulated by stimulus-stimulus, but not by stimulus-response incompatibilities.

PubMed

Cespón, J; Galdo-Álvarez, S; Díaz, F

2013-04-01

Studies of the N2pc in Simon-type tasks have revealed inconsistent results. That is, N2pc was only modulated when a stimulus-stimulus (S-S) overlap covaries with the stimulus-response (S-R) overlap. The present study aimed to establish whether N2pc is modulated by the S-R or by the S-S overlap. Therefore, we designed a Simon task requiring response to a colour stimulus (an arrow) with two irrelevant dimensions (position and direction). The following conditions were thus generated: compatible direction-compatible position (CDCP); incompatible direction-compatible position (IDCP); compatible direction-incompatible position (CDIP); and incompatible direction-incompatible position (IDIP). In IDCP and CDIP, both irrelevant dimensions conveyed contradictory spatial information (S-S incompatibility), while compatibility between both irrelevant dimensions occurred in CDCP and IDIP (the direction indicated was compatible with stimulus position). The N2pc amplitude was smaller in IDCP and CDIP than in CDCP and IDIP, what suggests that N2pc was modulated by S-S incompatibility and not by S-R incompatibilities. Copyright © 2013 Elsevier B.V. All rights reserved.

Odorants selectively activate distinct G protein subtypes in olfactory cilia.

PubMed

Schandar, M; Laugwitz, K L; Boekhoff, I; Kroner, C; Gudermann, T; Schultz, G; Breer, H

1998-07-03

Chemoelectrical signal transduction in olfactory neurons appears to involve intracellular reaction cascades mediated by heterotrimeric GTP-binding proteins. In this study attempts were made to identify the G protein subtype(s) in olfactory cilia that are activated by the primary (odorant) signal. Antibodies directed against the alpha subunits of distinct G protein subtypes interfered specifically with second messenger reponses elicited by defined subsets of odorants; odor-induced cAMP-formation was attenuated by Galphas antibodies, whereas Galphao antibodies blocked odor-induced inositol 1,4, 5-trisphosphate (IP3) formation. Activation-dependent photolabeling of Galpha subunits with [alpha-32P]GTP azidoanilide followed by immunoprecipitation using subtype-specific antibodies enabled identification of particular individual G protein subtypes that were activated upon stimulation of isolated olfactory cilia by chemically distinct odorants. For example odorants that elicited a cAMP response resulted in labeling of a Galphas-like protein, whereas odorants that elicited an IP3 response led to the labeling of a Galphao-like protein. Since odorant-induced IP3 formation was also blocked by Gbeta antibodies, activation of olfactory phospholipase C might be mediated by betagamma subunits of a Go-like G protein. These results indicate that different subsets of odorants selectively trigger distinct reaction cascades and provide evidence for dual transduction pathways in olfactory signaling.

Luteinizing hormone-releasing hormone (LHRH) in rat olfactory systems.

PubMed

Witkin, J W; Silverman, A J

1983-08-20

The luteinizing hormone-releasing hormone (LHRH) systems of rat olfactory bulbs and nasal areas were studied in neonatal and adult rats. Animals were perfused with Zamboni's fixative and olfactory bulbs with nasal olfactory areas intact were removed, postfixed, and decalcified. LHRH was immunohistochemically demonstrated in unembedded frozen or vibratome sections. Luteinizing hormone-releasing hormone immunoreactive elements were found along the course of the nervus terminalis (NT) and within both the main and accessory olfactory bulbs (MOB and AOB, respectively). Both LHRH neurons and fibers were present in the AOB, but only fibers were detected in the MOB. The fibers of the AOB were not confined to any particular lamina while fibers in the MOB were found mainly in the external plexiform layer. LHRH fibers were found in the mucosa of the olfactory epithelium of the vomeronasal organ in both neonatal and adult rats. The NT probably serves as a source of LHRH fibers for both the AOB and the MOB and for fibers observed in the olfactory epithelium of the vomeronasal organ. Other likely sources of LHRH fibers in the olfactory bulb are discussed.

Evaluation of olfactory function in adults with primary hypothyroidism.

PubMed

Günbey, Emre; Karlı, Rıfat; Gökosmanoğlu, Feyzi; Düzgün, Berkan; Ayhan, Emre; Atmaca, Hulusi; Ünal, Recep

2015-10-01

Sufficient clinical data are not available on the effect of hypothyroidism on olfactory function in adults. In this study, we aimed to evaluate the olfactory function of adult patients diagnosed with primary hypothyroidism. Forty-five patients aged between 18 and 60 years who were diagnosed with clinical primary hypothyroidism and 45 healthy controls who had normal thyroid function tests were included in the study. Sniffin' Sticks olfactory test results of the 2 groups were compared. The relationships between thyroid function tests and olfactory parameters were evaluated. Odor threshold, identification, and discrimination scores of the hypothyroid group were significantly lower than those of the control group (p < 0.001). A significant positive correlation was detected between free triiodothyronine (FT3) levels and odor threshold, identification, and discrimination scores (p < 0.001). There was no significant relationship between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and olfactory parameters. Our study revealed diminished olfactory function in adults with hypothyroidism. FT3 levels were found to have a more significant relationship with olfactory parameters than TSH or FT4 levels. © 2015 ARS-AAOA, LLC.

Olfactory function in psychotic disorders: Insights from neuroimaging studies

PubMed Central

Good, Kimberley P; Sullivan, Randii Lynn

2015-01-01

Olfactory deficits on measures of identification, familiarity, and memory are consistently noted in patients with psychotic disorders relative to age-matched controls. Olfactory intensity ratings, however, appear to remain intact while the data on hedonics and detection threshold are inconsistent. Despite the behavioral abnormalities noted, no specific regional brain hypoactivity has been identified in psychosis patients, for any of the olfactory domains. However, an intriguing finding emerged from this review in that the amygdala and pirifom cortices were not noted to be abnormal in hedonic processing (nor was the amygdala identified abnormal in any study) in psychotic disorders. This finding is in contrast to the literature in healthy individuals, in that this brain region is strongly implicated in olfactory processing (particularly for unpleasant odorants). Secondary olfactory cortex (orbitofrontal cortices, thalamus, and insula) was abnormally activated in the studies examined, particularly for hedonic processing. Further research, using consistent methodology, is required for better understanding the neurobiology of olfactory deficits. The authors suggest taking age and sex differences into consideration and further contrasting olfactory subgroups (impaired vs intact) to better our understanding of the heterogeneity of psychotic disorders. PMID:26110122

CT assessment of woodworkers' nasal adenocarcinomas confirms the origin in the olfactory cleft.

PubMed

Georgel, T; Jankowski, R; Henrot, P; Baumann, C; Kacha, S; Grignon, B; Toussaint, B; Graff, P; Kaminsky, M C; Geoffrois, L; Vignaud, J M

2009-08-01

Endoscopic endonasal surgery let us observe that woodworkers' nasal adenocarcinomas originate in the olfactory cleft. Our aim was the identification of CT imaging features that corroborate the olfactory cleft as the site of origin for woodworkers' adenocarcinoma. We designed a retrospective study to compare CT scans of 27 unilateral olfactory cleft adenocarcinomas with 30 cases of nasosinusal polyposis (NSP) and 33 healthy sinus controls. Enlargement of the olfactory cleft, lateralization of the ethmoidal turbinate wall, and contralateral bulging of the nasal septum were measured on coronal scans passing through crista galli and posterior half of both ocular globes. Comparisons have been performed by using analysis of variance and the Bonferroni procedure. The nasal septum was significantly bulging across the midline in adenocarcinoma (4.6 +/- 3 mm; range, -0.1-13.7 mm) compared with NSP (0.7 +/- 1 mm; range, -2.1-2.3 mm) or healthy sinus controls (0.5 +/- 1 mm; range, -1.2-2 mm) (P < .001). The olfactory cleft was significantly wider in adenocarcinoma (15.1 +/- 4.5 mm; range, 8.6-25.7 mm) than in NSP (3.6 +/- 0.4 mm; range, 2.8-4.6 mm) or healthy sinus controls (3.3 +/- 0.7 mm; range, 1.4-4.6 mm). The ethmoidal labyrinth width was significantly smaller on the pathologic side in adenocarcinoma (7.2 +/- 2.7 mm; range, 3.2-14.2 mm) than in the control groups (P < .001). Whereas the angle between the conchal lamina and vertical midline was close to zero degrees in NSP (0.03 +/- 2.25 degrees ; range, -5 degrees -3 degrees ) and healthy sinus controls (0.45 +/- 2.13 degrees , range, -5 degrees -5 degrees ), it reached 39.76 +/- 13.83 degrees (P < .001) in adenocarcinoma. Radiologists should suspect nasal adenocarcinoma on sinus CT scans showing a unilateral expanding opacity of the olfactory cavity.

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

ERIC Educational Resources Information Center

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…

An Investigation on the Role of Spike Latency in an Artificial Olfactory System

PubMed Central

Martinelli, Eugenio; Polese, Davide; Dini, Francesca; Paolesse, Roberto; Filippini, Daniel; Lundström, Ingemar; Di Natale, Corrado

2011-01-01

Experimental studies have shown that the reactions to external stimuli may appear only few hundreds of milliseconds after the physical interaction of the stimulus with the proper receptor. This behavior suggests that neurons transmit the largest meaningful part of their signal in the first spikes, and than that the spike latency is a good descriptor of the information content in biological neural networks. In this paper this property has been investigated in an artificial sensorial system where a single layer of spiking neurons is trained with the data generated by an artificial olfactory platform based on a large array of chemical sensors. The capability to discriminate between distinct chemicals and mixtures of them was studied with spiking neural networks endowed with and without lateral inhibitions and considering as output feature of the network both the spikes latency and the average firing rate. Results show that the average firing rate of the output spikes sequences shows the best separation among the experienced vapors, however the latency code is able in a shorter time to correctly discriminate all the tested volatile compounds. This behavior is qualitatively similar to those recently found in natural olfaction, and noteworthy it provides practical suggestions to tail the measurement conditions of artificial olfactory systems defining for each specific case a proper measurement time. PMID:22194721

An Olfactory Indicator for Acid-Base Titrations.

ERIC Educational Resources Information Center

Flair, Mark N.; Setzer, William N.

1990-01-01

The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

Olfactory gene expression in migrating adult sockeye salmon Oncorhynchus nerka.

PubMed

Bett, N N; Hinch, S G; Kaukinen, K H; Li, S; Miller, K M

2018-04-16

Expression of 12 olfactory genes was analysed in adult sockeye salmon Oncorhynchus nerka nearing spawning grounds and O. nerka that had strayed from their natal migration route. Variation was found in six of these genes, all of which were olfc olfactory receptors and had lower expression levels in salmon nearing spawning grounds. The results may reflect decreased sensitivity to natal water olfactory cues as these fish are no longer seeking the correct migratory route. The expression of olfactory genes during the olfactory-mediated spawning migration of Pacific salmon Oncorhynchus spp. is largely unexplored and these findings demonstrate a link between migratory behaviours and olfactory plasticity that provides a basis for future molecular research on salmon homing. © 2018 The Fisheries Society of the British Isles.

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

NASA Astrophysics Data System (ADS)

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.

Assessment of olfactory threshold in patients undergoing radiotherapy for head and neck malignancies.

PubMed

Jalali, Mir Mohammad; Gerami, Hooshang; Rahimi, Abbas; Jafari, Manizheh

2014-10-01

Radiotherapy is a common treatment modality for patients with head and neck malignancies. As the nose lies within the field of radiotherapy of the head and neck, the olfactory fibers and olfactory receptors may be affected by radiation. The aim of this study was to evaluate changes in olfactory threshold in patients with head and neck malignancies who have received radiation to the head and neck. The olfactory threshold of patients with head and neck malignancies was assessed prospectively before radiation therapy and serially for up to 6 months after radiotherapy using sniff bottles. In vivo dosimetry was performed using 82 LiF (MCP) chips and a thermoluminescent dosimeter (TLD) system. Sixty-one patients were recruited before radiotherapy was commenced. Seven patients did not return for evaluation after radiation. Fifty-four patients were available for follow-up assessment (28 women, 26 men; age, 22-86 years; median, 49 years). Total radiation dose was 50.1 Gy (range, 30-66 Gy). Mean olfactory threshold scores were found to deteriorate significantly at various timepoints after radiotherapy (11.7 before radiotherapy versus 4.0 at Month 6, general linear model, P<0.0001). With in vivo dosimetry, we found that the median measured dose to the olfactory area was 334 µC. We also identified a cutoff point according to the dose to the olfactory epithelium. Olfactory threshold was significantly decreased 2-6 weeks after initiation of therapy, with cumulative local radiation >135 µC (Mann-Whitney U test, P=0.01). Deterioration in olfactory threshold scores was found at 6 months after initiation of radiation therapy. Provided that these results are reproducible, an evaluation of olfactory functioning in patients with head and neck malignancies using in vivo dosimetry may be useful for determining the optimal dose for patients treated with conformal radiotherapy techniques while avoiding the side effects of radiation.

Smelling time: a neural basis for olfactory scene analysis

PubMed Central

Ache, Barry W.; Hein, Andrew M.; Bobkov, Yuriy V.; Principe, Jose C.

2016-01-01

Behavioral evidence from phylogenetically diverse animals and humans suggests that olfaction could be much more involved in interpreting space and time than heretofore imagined by extracting temporal information inherent in the olfactory signal. If this is the case, the olfactory system must have neural mechanisms capable of encoding time at intervals relevant to the turbulent odor world in which many animals live. We review evidence that animals can use populations of rhythmically active or ‘bursting’ olfactory receptor neurons (bORNs) to extract and encode temporal information inherent in natural olfactory signals. We postulate that bORNs represent an unsuspected neural mechanism through which time can be accurately measured, and that ‘smelling time’ completes the requirements for true olfactory scene analysis. PMID:27594700

QSPR modeling of octanol/water partition coefficient for vitamins by optimal descriptors calculated with SMILES.

PubMed

Toropov, A A; Toropova, A P; Raska, I

2008-04-01

Simplified molecular input line entry system (SMILES) has been utilized in constructing quantitative structure-property relationships (QSPR) for octanol/water partition coefficient of vitamins and organic compounds of different classes by optimal descriptors. Statistical characteristics of the best model (vitamins) are the following: n=17, R(2)=0.9841, s=0.634, F=931 (training set); n=7, R(2)=0.9928, s=0.773, F=690 (test set). Using this approach for modeling octanol/water partition coefficient for a set of organic compounds gives a model that is statistically characterized by n=69, R(2)=0.9872, s=0.156, F=5184 (training set) and n=70, R(2)=0.9841, s=0.179, F=4195 (test set).

Retinoic Acid Is Present in the Postnatal Rat Olfactory Organ and Persists in Vitamin A–Depleted Neural Tissue1–3

PubMed Central

Asson-Batres, Mary Ann; Smith, W. Bradford; Clark, Gale

2009-01-01

Vitamin A (VA), all-trans-retinol (at-ROL), and its derivative, all-trans-retinoic acid (at-RA), are required for neuron development. The effects of these retinoids are dependent upon the nutritional status of the rat and tissue-specific dynamics of retinoid access and utilization. The purpose of this study was to determine the status of at-ROL and at-RA in the peripheral olfactory organ of postnatal rats fed a normal diet and rats fed a VA-deficient (VAD) diet. Extracted retinoids were analyzed by HPLC. Resolved sample peaks were identified by comparing their elution times and spectra with those of authentic standards. Mean at-RA and at-ROL concentrations of 23 pmol/g olfactory tissue and 0.13 nmol/g, respectively, were recovered from olfactory tissue. The ratio of at-RA:at-ROL in olfactory was ∼2 times that in testis and 200 times that in liver. at-ROL was depleted from the liver and olfactory organ of rats fed a VAD diet from birth to 70 d of age. Surprisingly, at-RA was still present in olfactory tissue from these rats. At 90 d of age, the VAD rats were frankly deficient and at-RA was no longer detectable in olfactory tissue. The comparatively high ratio of at-RA:at-ROL in the peripheral olfactory organ and the persistence of at-RA in at-ROL-depleted tissues strongly suggests that maintenance of local stores of at-RA is functionally relevant in this tissue. PMID:19403718

Olfactory conditioned same-sex partner preference in female rats: Role of ovarian hormones.

PubMed

Tecamachaltzi-Silvaran, M B; Barradas-Moctezuma, M; Herrera-Covarrubias, D; Carrillo, P; Corona-Morales, A A; Perez, C A; García, L I; Manzo, J; Coria-Avila, Genaro A

2017-11-01

The dopamine D2-type receptor agonist quinpirole (QNP) facilitates the development of conditioned same-sex partner preference in males during cohabitation, but not in ovariectomized (OVX) females, primed with estradiol benzoate (EB) and progesterone (P). Herein we tested the effects of QNP on OVX, EB-only primed females. Females received a systemic injection (every four days) of either saline (Saline-conditioned) or QNP (QNP-conditioned) and then cohabited for 24h with lemon-scented stimulus females (CS+), during three trials. In test 1 (female-female) preference was QNP-free, and females chose between the CS+ female and a novel female. In test 2 (male-female) they chose between the CS+ female and a sexually experienced male. In test 1 Saline-conditioned females displayed more hops & darts towards the novel female, but QNP-conditioned females displayed more sexual solicitations towards the CS+ female. In test 2 Saline-conditioned females displayed a clear preference for the male, whereas QNP-conditioned females displayed what we considered a bisexual preference. We discuss the effect of dopamine and ovarian hormones on the development of olfactory conditioned same-sex preference in females. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical factors determine olfactory system beta oscillations in waking rats.

PubMed

Lowry, Catherine A; Kay, Leslie M

2007-07-01

Recent studies have pointed to olfactory system beta oscillations of the local field potential (15-30 Hz) and their roles both in learning and as specific responses to predator odors. To describe odorant physical properties, resultant behavioral responses and changes in the central olfactory system that may induce these oscillations without associative learning, we tested rats with 26 monomolecular odorants spanning 6 log units of theoretical vapor pressure (estimate of relative vapor phase concentration) and 10 different odor mixtures. We found odorant vapor phase concentration to be inversely correlated with investigation time on the first presentation, after which investigation times were brief and not different across odorants. Analysis of local field potentials from the olfactory bulb and anterior piriform cortex shows that beta oscillations in waking rats occur specifically in response to the class of volatile organic compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the first three to four presentations and are weakly present for some odorants in anesthetized rats. Gamma oscillations show a smaller effect that is not restricted to the same range of odorants. Olfactory bulb theta oscillations were also examined as a measure of effective afferent input strength, and the power of these oscillations did not vary systematically with vapor pressure, suggesting that it is not olfactory bulb drive strength that determines the presence of beta oscillations. Theta band coherence analysis shows that coupling strength between the olfactory bulb and piriform cortex increases linearly with vapor phase concentration, which may facilitate beta oscillations above a threshold.

Levels-of-processing effects on a task of olfactory naming.

PubMed

Royet, Jean-Pierre; Koenig, Olivier; Paugam-Moisy, Helene; Puzenat, Didier; Chasse, Jean-Luc

2004-02-01

The effects of odor processing were investigated at various analytical levels, from simple sensory analysis to deep or semantic analysis, on a subsequent task of odor naming. Students (106 women, 23.6 +/- 5.5 yr. old; 65 men, 25.1 +/- 7.1 yr. old) were tested. The experimental procedure included two successive sessions, a first session to characterize a set of 30 odors with criteria that used various depths of processing and a second session to name the odors as quickly as possible. Four processing conditions rated the odors using descriptors before naming the odor. The control condition did not rate the odors before naming. The processing conditions were based on lower-level olfactory judgments (superficial processing), higher-level olfactory-gustatory-somesthetic judgments (deep processing), and higher-level nonolfactory judgments (Deep-Control processing, with subjects rating odors with auditory and visual descriptors). One experimental condition successively grouped lower- and higher-level olfactory judgments (Superficial-Deep processing). A naming index which depended on response accuracy and the subjects' response time were calculated. Odor naming was modified for 18 out of 30 odorants as a function of the level of processing required. For 94.5% of significant variations, the scores for odor naming were higher following those tasks for which it was hypothesized that the necessary olfactory processing was carried out at a deeper level. Performance in the naming task was progressively improved as follows: no rating of odors, then superficial, deep-control, deep, and superficial-deep processings. These data show that the deepest olfactory encoding was later associated with progressively higher performance in naming.

Differential effects of unilateral olfactory deprivation on noradrenergic and cholinergic systems in the main olfactory bulb of the rat.

PubMed

Gómez, C; Briñón, J G; Colado, M I; Orio, L; Vidal, M; Barbado, M V; Alonso, J R

2006-09-15

The lack of environmental olfactory stimulation produced by sensory deprivation causes significant changes in the deprived olfactory bulb. Olfactory transmission in the main olfactory bulb (MOB) is strongly modulated by centrifugal systems. The present report examines the effects of unilateral deprivation on the noradrenergic and cholinergic centrifugal systems innervating the MOB. The morphology, distribution, and density of positive axons were studied in the MOBs of control and deprived rats, using dopamine-beta-hydroxylase (DBH)-immunohistochemistry and acetylcholinesterase (AChE) histochemistry in serial sections. Catecholamine content was compared among the different groups of MOBs (control, contralateral, and ipsilateral to the deprivation) using high-performance liquid chromatography analysis. Sensory deprivation revealed that the noradrenergic system developed adaptive plastic changes after olfactory deprivation, including important modifications in its fiber density and distribution, while no differences in cholinergic innervation were observed under the same conditions. The noradrenergic system underwent an important alteration in the glomerular layer, in which some glomeruli showed a dense noradrenergic innervation that was not detected in control animals. The DBH-positive glomeruli with the highest noradrenergic fiber density were compared with AChE-stained sections and it was observed that the strongly noradrenergic-innervated glomeruli were always atypical glomeruli (characterized by their strong degree of cholinergic innervation). In addition to the morphological findings, our biochemical data revealed that olfactory deprivation caused a decrease in the content of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid in the ipsilateral MOB in comparison to the contralateral and control MOBs, together with an increase in noradrenaline levels in both the ipsilateral and contralateral MOBs. Our results show that regulation of the noradrenergic

Optimised method to estimate octanol water distribution coefficient (logD) in a high throughput format.

PubMed

Low, Ying Wei Ivan; Blasco, Francesca; Vachaspati, Prakash

2016-09-20

Lipophilicity is one of the molecular properties assessed in early drug discovery. Direct measurement of the octanol-water distribution coefficient (logD) requires an analytical method with a large dynamic range or multistep dilutions, as the analyte's concentrations span across several orders of magnitude. In addition, water/buffer and octanol phases which have very different polarity could lead to matrix effects and affect the LC-MS response, leading to erroneous logD values. Most compound libraries use DMSO stocks as it greatly reduces the sample requirement but the presence of DMSO has been shown to underestimate the lipophilicity of the analyte. The present work describes the development of an optimised shake flask logD method using deepwell 96 well plate that addresses the issues related to matrix effects, DMSO concentration and incubation conditions and is also amenable to high throughput. Our results indicate that the equilibrium can be achieved within 30min by flipping the plate on its side while even 0.5% of DMSO is not tolerated in the assay. This study uses the matched matrix concept to minimise the errors in analysing the two phases namely buffer and octanol in LC-MS. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of octanol on penicillin induced epileptiform activity in rats: an in vivo study.

PubMed

Bostanci, M Omer; Bağirici, Faruk

2006-10-01

The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.

Olfactory CNG channel desensitization by Ca2+/CaM via the B1b subunit affects response termination but not sensitivity to recurring stimulation.

PubMed

Song, Yijun; Cygnar, Katherine D; Sagdullaev, Botir; Valley, Matthew; Hirsh, Sarah; Stephan, Aaron; Reisert, Johannes; Zhao, Haiqing

2008-05-08

Ca2+/calmodulin-mediated negative feedback is a prototypical regulatory mechanism for Ca2+-permeable ion channels. In olfactory sensory neurons (OSNs), such regulation on the cyclic nucleotide-gated (CNG) channel is considered a major mechanism of OSN adaptation. To determine the role of Ca2+/calmodulin desensitization of the olfactory CNG channel, we introduced a mutation in the channel subunit CNGB1b in mice that rendered the channel resistant to fast desensitization by Ca2+/calmodulin. Contrary to expectations, mutant OSNs showed normal receptor current adaptation to repeated stimulation. Rather, they displayed slower response termination and, consequently, reduced ability to transmit olfactory information to the olfactory bulb. They also displayed reduced response decline during sustained odorant exposure. These results suggest that Ca2+/calmodulin-mediated CNG channel fast desensitization is less important in regulating the sensitivity to recurring stimulation than previously thought and instead functions primarily to terminate OSN responses.

Olfactory Cued Learning Paradigm.

PubMed

Liu, Gary; McClard, Cynthia K; Tepe, Burak; Swanson, Jessica; Pekarek, Brandon; Panneerselvam, Sugi; Arenkiel, Benjamin R

2017-05-05

Sensory stimulation leads to structural changes within the CNS (Central Nervous System), thus providing the fundamental mechanism for learning and memory. The olfactory circuit offers a unique model for studying experience-dependent plasticity, partly due to a continuous supply of integrating adult born neurons. Our lab has recently implemented an olfactory cued learning paradigm in which specific odor pairs are coupled to either a reward or punishment to study downstream circuit changes. The following protocol outlines the basic set up for our learning paradigm. Here, we describe the equipment setup, programming of software, and method of behavioral training.

The Evaluation of Olfactory Function in Patients With Schizophrenia.

PubMed

Robabeh, Soleimani; Mohammad, Jalali Mir; Reza, Ahmadi; Mahan, Badri

2015-04-23

The aim of this study was to compare olfactory threshold, smell identification, intensity and pleasantness ratings between patients with schizophrenia and healthy controls, and (2) to evaluate correlations between ratings of olfactory probes and illness characteristics. Thirty one patients with schizophrenia and 31 control subjects were assessed with the olfactory n-butanol threshold test, the Iran smell identification test (Ir-SIT), and the suprathreshold amyl acetate odor intensity and odor pleasantness rating test. All olfactory tasks were performed unirhinally. Patients with schizophrenia showed disrupted olfaction in all four measures. Longer duration of schizophrenia was associated with a larger impairment of olfactory threshold or microsmic range on the Ir-SIT (P=0.04, P=0.05, respectively). In patients with schizophrenia, female subjects' ratings of pleasantness followed the same trend as control subjects, whereas male patients' ratings showed an opposite trend. Patients exhibiting high positive score on the positive and negative syndrome scale (PANSS) performed better on the olfactory threshold test (r=0.37, P=0.04). The higher odor pleasantness ratings of patients were associated with presence of positive symptoms. The results suggest that both male and female patients with schizophrenia had difficulties on the olfactory threshold and smell identification tests, but appraisal of odor pleasantness was more disrupted in male patients.

Involvement of hormones in olfactory imprinting and homing in chum salmon.

PubMed

Ueda, Hiroshi; Nakamura, Shingo; Nakamura, Taro; Inada, Kaoru; Okubo, Takashi; Furukawa, Naohiro; Murakami, Reiichi; Tsuchida, Shigeo; Zohar, Yonathan; Konno, Kotaro; Watanabe, Masahiko

2016-02-16

The olfactory hypothesis for salmon imprinting and homing to their natal stream is well known, but the endocrine hormonal control mechanisms of olfactory memory formation in juveniles and retrieval in adults remain unclear. In brains of hatchery-reared underyearling juvenile chum salmon (Oncorhynchus keta), thyrotropin-releasing hormone gene expression increased immediately after release from a hatchery into the natal stream, and the expression of the essential NR1 subunit of the N-methyl-D-aspartate receptor increased during downstream migration. Gene expression of salmon gonadotropin-releasing hormone (sGnRH) and NR1 increased in the adult chum salmon brain during homing from the Bering Sea to the natal hatchery. Thyroid hormone treatment in juveniles enhanced NR1 gene activation, and GnRHa treatment in adults improved stream odour discrimination. Olfactory memory formation during juvenile downstream migration and retrieval during adult homing migration of chum salmon might be controlled by endocrine hormones and could be clarified using NR1 as a molecular marker.

Increase of olfactory threshold in plating factory workers exposed to chromium in Korea.

PubMed

Kitamura, Fumihiko; Yokoyama, Kazuhito; Araki, Shunichi; Nishikitani, Mariko; Choi, Jae-Wook; Yum, Youg-Tae; Park, Hee-Chan; Park, Sang-Hwoi; Sato, Hajime

2003-07-01

To disclose the effects of chromium (Cr) on olfactory function, olfactory threshold tests were conducted on 27 male plating workers (Cr workers) with signs and symptoms of olfactory irritation but without nasal septum perforation or ulcer and on 34 male control subjects in Korean plating factories. The Cr workers had been exposed to Cr fume for 0.9 to 18.2 (mean 7.9) years; their blood Cr concentrations (0.16-3.69, mean 1.29 microg/dl) were significantly higher than those of the 34 control subjects (0.04-1.95, mean 0.55 microg/dl). Scores on recognition thresholds among the Cr workers were significantly higher than those of the control subjects (p < 0.05) and related positively and significantly to the exposure periods of the 27 Cr workers (p < 0.05). Olfactory thresholds were not significantly different between the Cr workers with and without nasal signs or symptoms, except that the scores on the recognition threshold were significantly higher in those experiencing difficulty with smell (p < 0.05). It is suggested that olfactory threshold is affected by Cr without development of nasal septum perforation or ulceration.

Chemosensory interaction: acquired olfactory impairment is associated with decreased taste function.

PubMed

Landis, Basile N; Scheibe, Mandy; Weber, Cornelia; Berger, Robert; Brämerson, Annika; Bende, Mats; Nordin, Steven; Hummel, Thomas

2010-08-01

Olfaction, taste and trigeminal function are three distinct modalities. However, in daily life they are often activated concomitantly. In health and disease, it has been shown that in two of these senses, the trigeminal and olfactory senses, modification of one sense leads to changes in the other sense and vice versa. The objective of the study was to investigate whether and (if so) how, the third modality, taste, is influenced by olfactory impairment. We tested 210 subjects with normal (n = 107) or impaired (n = 103) olfactory function for their taste identification capacities. Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, Taste Strips). In an additional experiment, healthy volunteers underwent reversible olfactory cleft obstruction to investigate short-time changes of gustatory function after olfactory alteration. Mean gustatory identification (taste strip score) for the subjects with impaired olfaction was 19.4 +/- 0.6 points and 22.9 +/- 0.5 points for those with normal olfactory function (t = 4.6, p < 0.001). The frequencies of both, smell and taste impairments interacted significantly (Chi(2), F = 16.4, p < 0.001), and olfactory and gustatory function correlated (r (210) = 0.30, p < 0.001). Neither age nor olfactory impairment cause effects interfered with this olfactory-gustatory interaction. In contrast, after short-lasting induced olfactory decrease, gustatory function remained unchanged. The present study suggests that longstanding impaired olfactory function is associated with decreased gustatory function. These findings seem to extend previously described mutual chemosensory interactions also to smell and taste. It further raises the question whether chemical senses in general decrease mutually after acquired damage.

Olfactory epithelium influences the orientation of mitral cell dendrites during development.

PubMed

López-Mascaraque, Laura; García, Concepción; Blanchart, Albert; De Carlos, Juan A

2005-02-01

We have established previously that, although the olfactory epithelium is absent in the homozygous Pax-6 mutant mouse, an olfactory bulb-like structure (OBLS) does develop. Moreover, this OBLS contains cells that correspond to mitral cells, the primary projection neurons in the olfactory bulb. The current study aimed to address whether the dendrites of mitral cells in the olfactory bulb or in the OBLS mitral-like cells, exhibit a change in orientation in the presence of the olfactory epithelium. The underlying hypothesis is that the olfactory epithelium imparts a trophic signal on mitral and mitral-like cell that influences the growth of their primary dendrites, orientating them toward the surface of the olfactory bulb. Hence, we cultured hemibrains from wild-type and Pax 6 mutant mice from two different embryonic stages (embryonic days 14 and 15) either alone or in coculture with normal olfactory epithelial explants or control tissue (cerebellum). Our results indicate that the final dendritic orientation of mitral and mitral-like cells is directly influenced both by age and indeed by the presence of the olfactory epithelium. Copyright 2004 Wiley-Liss, Inc.

5HTR3A-driven GFP labels immature olfactory sensory neurons.

PubMed

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

2017-05-01

The ionotropic serotonin receptor, 5-HT 3 , 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-HT 3 is expressed in the adult epithelium. Using a transgenic mouse in which the promoter for the 5-HT 3a 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-HT 3a mRNA and GFP are expressed within globose basal cells of the olfactory and vomeronasal epithelium in adult mice. Whereas the 5-HT 3a 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-HT 3a is indicative of a proliferative or developmental state, regardless of age, and that the 5-HT 3A 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.

Postnatal odorant exposure induces peripheral olfactory plasticity at the cellular level.

PubMed

Cadiou, Hervé; Aoudé, Imad; Tazir, Bassim; Molinas, Adrien; Fenech, Claire; Meunier, Nicolas; Grosmaitre, Xavier

2014-04-02

Mammalian olfactory sensory neurons (OSNs) form the primary elements of the olfactory system. Inserted in the olfactory mucosa lining of the nasal cavity, they are exposed to the environment and their lifespan is brief. Several reports say that OSNs are regularly regenerated during the entire life and that odorant environment affects the olfactory epithelium. However, little is known about the impact of the odorant environment on OSNs at the cellular level and more precisely in the context of early postnatal olfactory exposure. Here we exposed MOR23-green fluorescent protein (GFP) and M71-GFP mice to lyral or acetophenone, ligands for MOR23 or M71, respectively. Daily postnatal exposure to lyral induces plasticity in the population of OSNs expressing MOR23. Their density decreases after odorant exposure, whereas the amount of MOR23 mRNA and protein remain stable in the whole epithelium. Meanwhile, quantitative PCR indicates that each MOR23 neuron has higher levels of olfactory receptor transcripts and also expresses more CNGA2 and phosphodiesterase 1C, fundamental olfactory transduction pathway proteins. Transcript levels return to baseline after 4 weeks recovery. Patch-clamp recordings reveal that exposed MOR23 neurons respond to lyral with higher sensitivity and broader dynamic range while the responses' kinetics were faster. These effects are specific to the odorant-receptor pair lyral-MOR23: there was no effect of acetophenone on MOR23 neurons and no effect of acetophenone and lyral on the M71 population. Together, our results clearly demonstrate that OSNs undergo specific anatomical, molecular, and functional adaptation when chronically exposed to odorants in the early stage of life.

Bone marrow chimeric mice reveal a role for CX₃CR1 in maintenance of the monocyte-derived cell population in the olfactory neuroepithelium.

PubMed

Vukovic, Jana; Blomster, Linda V; Chinnery, Holly R; Weninger, Wolfgang; Jung, Steffen; McMenamin, Paul G; Ruitenberg, Marc J

2010-10-01

Macrophages in the olfactory neuroepithelium are thought to play major roles in tissue homeostasis and repair. However, little information is available at present about possible heterogeneity of these monocyte-derived cells, their turnover rates, and the role of chemokine receptors in this process. To start addressing these issues, this study used Cx₃cr1(gfp) mice, in which the gene sequence for eGFP was knocked into the CX₃CR1 gene locus in the mutant allele. Using neuroepithelial whole-mounts from Cx₃cr1(gfp/+) mice, we show that eGFP(+) cells of monocytic origin are distributed in a loose network throughout this tissue and can be subdivided further into two immunophenotypically distinct subsets based on MHC-II glycoprotein expression. BM chimeric mice were created using Cx₃cr1(gfp/+) donors to investigate turnover of macrophages (and other monocyte-derived cells) in the olfactory neuroepithelium. Our data indicate that the monocyte-derived cell population in the olfactory neuroepithelium is actively replenished by circulating monocytes and under the experimental conditions, completely turned over within 6 months. Transplantation of Cx₃cr1(gfp/gfp) (i.e., CX₃CR1-deficient) BM partially impaired the replenishment process and resulted in an overall decline of the total monocyte-derived cell number in the olfactory epithelium. Interestingly, replenishment of the CD68(low)MHC-II(+) subset appeared minimally affected by CX₃CR1 deficiency. Taken together, the established baseline data about heterogeneity of monocyte-derived cells, their replenishment rates, and the role of CX₃CR1 provide a solid basis to further examine the importance of different monocyte subsets for neuroregeneration at this unique frontier with the external environment.

Modeling Olfactory Bulb Evolution through Primate Phylogeny

PubMed Central

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. PMID:25426851

Matching- and Nonmatching-to-Sample Concept Learning in Rats Using Olfactory Stimuli

ERIC Educational Resources Information Center

April, L. Brooke; Bruce, Katherine; Galizio, Mark

2011-01-01

Previous research has shown that rats can learn matching-to-sample relations with olfactory stimuli; however, the specific characteristics of this relational control are unclear. In Experiment 1, 6 rats were trained to either match or nonmatch to sample in a modified operant chamber using common household spices as olfactory stimuli. After…

Gender-typical olfactory regulation of sexual behavior in goldfish

PubMed Central

Kawaguchi, Yutaro; Nagaoka, Akira; Kitami, Asana; Mitsuhashi, Tomomi; Hayakawa, Youichi; Kobayashi, Makito

2014-01-01

It is known that olfaction is essential for the occurrence of sexual behavior in male goldfish. Sex pheromones from ovulatory females elicit male sexual behavior, chasing, and sperm releasing act. In female goldfish, ovarian prostaglandin F2α (PGF) elicits female sexual behavior, egg releasing act. It has been considered that olfaction does not affect sexual behavior in female goldfish. In the present study, we re-examined the involvement of olfaction in sexual behavior of female goldfish. Olfaction was blocked in male and female goldfish by two methods: nasal occlusion (NO) which blocks the reception of olfactants, and olfactory tract section (OTX) which blocks transmission of olfactory information from the olfactory bulb to the telencephalon. Sexual behavior of goldfish was induced by administration of PGF to females, an established method for inducing goldfish sexual behavior in both sexes. Sexual behavior in males was suppressed by NO and OTX as previously reported because of lack of pheromone stimulation. In females, NO suppressed sexual behavior but OTX did not affect the occurrence of sexual behavior. Females treated with both NO and OTX performed sexual behavior normally. These results indicate that olfaction is essential in female goldfish to perform sexual behavior as in males but in a different manner. The lack of olfaction in males causes lack of pheromonal stimulation, resulting in no behavior elicited. Whereas the results of female experiments suggest that lack of olfaction in females causes strong inhibition of sexual behavior mediated by the olfactory pathway. Olfactory tract section is considered to block the pathway and remove this inhibition, resulting in the resumption of the behavior. By subtract sectioning of the olfactory tract, it was found that this inhibition was mediated by the medial olfactory tracts, not the lateral olfactory tracts. Thus, it is concluded that goldfish has gender-typical olfactory regulation for sexual behavior. PMID

Electro-olfactogram and multiunit olfactory receptor responses to binary and trinary mixtures of amino acids in the channel catfish, Ictalurus punctatus

PubMed Central

1989-01-01

In vivo electrophysiological recordings from populations of olfactory receptor neurons in the channel catfish, Ictalurus punctatus, clearly showed that responses to binary and trinary mixtures of amino acids were predictable with knowledge obtained from previous cross-adaptation studies of the relative independence of the respective binding sites of the component stimuli. All component stimuli, from which equal aliquots were drawn to form the mixtures, were adjusted in concentration to provide for approximately equal response magnitudes. The magnitude of the response to a mixture whose component amino acids showed significant cross-reactivity was equivalent to the response to any single component used to form that mixture. A mixture whose component amino acids showed minimal cross-adaptation produced a significantly larger relative response than a mixture whose components exhibited considerable cross-reactivity. This larger response approached the sum of the responses to the individual component amino acids tested at the resulting concentrations in the mixture, even though olfactory receptor dose-response functions for amino acids in this species are characterized by extreme sensory compression (i.e., successive concentration increments produce progressively smaller physiological responses). Thus, the present study indicates that the response to sensory stimulation of olfactory receptor sites is more enhanced by the activation of different receptor site types than by stimulus interaction at a single site type. PMID:2703818

Long term serious olfactory loss in colds and/or flu.

PubMed

de Haro-Licer, Josep; Roura-Moreno, Jordi; Vizitiu, Anabella; González-Fernández, Adela; González-Ares, Josep Antón

2013-01-01

In the general population, we can find 2-3% of lifelong olfactory disorders (from hyposmia to anosmia). Two of the most frequent aetiologies are the common cold and flu. The aim of this study was to show the degree of long-term olfactory dysfunction caused by a cold or flu. This study was based on 240 patients, with olfactory loss caused only by flu or a cold. We excluded all patients with concomitant illness (66 patients), the rest of patients (n=174) consisted of 51 men (29.3%) and 123 women (70.7%). They all underwent olfactometry study (i and v cranial nerve) and a nasal sinus computed tomography scan, as well as magnetic resonance imaging of the brain. Results were compared with a control group (n=120). Very significant differences in levels of olfactory impairment for the olfactory nerve (P<.00001) and trigeminal nerve (P<.0001) were confirmed. People that suffer olfactory dysfunction for more than 6 months, from flu or a cold, present serious impairment of olfactory abilities. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Nested Expression Domains for Odorant Receptors in Zebrafish Olfactory Epithelium

NASA Astrophysics Data System (ADS)

Weth, Franco; Nadler, Walter; Korsching, Sigrun

1996-11-01

The mapping of high-dimensional olfactory stimuli onto the two-dimensional surface of the nasal sensory epithelium constitutes the first step in the neuronal encoding of olfactory input. We have used zebrafish as a model system to analyze the spatial distribution of odorant receptor molecules in the olfactory epithelium by quantitative in situ hybridization. To this end, we have cloned 10 very divergent zebrafish odorant receptor molecules by PCR. Individual genes are expressed in sparse olfactory receptor neurons. Analysis of the position of labeled cells in a simplified coordinate system revealed three concentric, albeit overlapping, expression domains for the four odorant receptors analyzed in detail. Such regionalized expression should result in a corresponding segregation of functional response properties. This might represent the first step of spatial encoding of olfactory input or be essential for the development of the olfactory system.

Carving Executive Control At Its Joints: Working Memory Capacity Predicts Stimulus-Stimulus, But Not Stimulus-Response, Conflict

PubMed Central

Meier, Matt E.; Kane, Michael J.

2015-01-01

Three experiments examined the relation between working memory capacity (WMC) and two different forms of cognitive conflict: stimulus-stimulus (S-S) and stimulus-response (SR) interference. Our goal was to test whether WMC’s relation to conflict-task performance is mediated by stimulus-identification processes (captured by S-S conflict), response-selection processes (captured by S-R conflict), or both. In Experiment 1, subjects completed a single task presenting both S-S and S-R conflict trials, plus trials that combined the two conflict types. We limited ostensible goal-maintenance contributions to performance by requiring the same goal for all trial types and by presenting frequent conflict trials that reinforced the goal. WMC predicted resolution of S-S conflict as expected: Higher-WMC subjects showed reduced response time interference. Although WMC also predicted S-R interference, here, higher-WMC subjects showed increased error interference. Experiment 2A replicated these results in a version of the conflict task without combined S-S/S-R trials. Experiment 2B increased the proportion of congruent (non-conflict) trials to promote reliance on goal-maintenance processes. Here, higher-WMC subjects resolved both S-S and S-R conflict more successfully than did lower-WMC subjects. The results were consistent with Kane and Engle’s (2003) two-factor theory of cognitive control, according to which WMC predicts executive-task performance through goal-maintenance and conflict-resolution processes. However, the present results add specificity to the account by suggesting that higher-WMC subjects better resolve cognitive conflict because they more efficiently select relevant stimulus features against irrelevant, distracting ones. PMID:26120774

Carving executive control at its joints: Working memory capacity predicts stimulus-stimulus, but not stimulus-response, conflict.

PubMed

Meier, Matt E; Kane, Michael J

2015-11-01

Three experiments examined the relation between working memory capacity (WMC) and 2 different forms of cognitive conflict: stimulus-stimulus (S-S) and stimulus-response (S-R) interference. Our goal was to test whether WMC's relation to conflict-task performance is mediated by stimulus-identification processes (captured by S-S conflict), response-selection processes (captured by S-R conflict), or both. In Experiment 1, subjects completed a single task presenting both S-S and S-R conflict trials, plus trials that combined the 2 conflict types. We limited ostensible goal-maintenance contributions to performance by requiring the same goal for all trial types and by presenting frequent conflict trials that reinforced the goal. WMC predicted resolution of S-S conflict as expected: Higher WMC subjects showed reduced response time interference. Although WMC also predicted S-R interference, here, higher WMC subjects showed increased error interference. Experiment 2A replicated these results in a version of the conflict task without combined S-S/S-R trials. Experiment 2B increased the proportion of congruent (nonconflict) trials to promote reliance on goal-maintenance processes. Here, higher WMC subjects resolved both S-S and S-R conflict more successfully than did lower WMC subjects. The results were consistent with Kane and Engle's (2003) 2-factor theory of cognitive control, according to which WMC predicts executive-task performance through goal-maintenance and conflict-resolution processes. However, the present results add specificity to the account by suggesting that higher WMC subjects better resolve cognitive conflict because they more efficiently select relevant stimulus features against irrelevant, distracting ones. (c) 2015 APA, all rights reserved).

The number of functional olfactory receptor genes and the relative size of olfactory brain structures are poor predictors of olfactory discrimination performance with enantiomers.

PubMed

Laska, Matthias; Genzel, Daria; Wieser, Alexandra

2005-02-01

The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.

Olfactory circuits and behaviors of nematodes.

PubMed

Rengarajan, Sophie; Hallem, Elissa A

2016-12-01

Over one billion people worldwide are infected with parasitic nematodes. Many parasitic nematodes actively search for hosts to infect using volatile chemical cues, so understanding the olfactory signals that drive host seeking may elucidate new pathways for preventing infections. The free-living nematode Caenorhabditis elegans is a powerful model for parasitic nematodes: because sensory neuroanatomy is conserved across nematode species, an understanding of the microcircuits that mediate olfaction in C. elegans may inform studies of olfaction in parasitic nematodes. Here we review circuit mechanisms that allow C. elegans to respond to odorants, gases, and pheromones. We also highlight work on the olfactory behaviors of parasitic nematodes that lays the groundwork for future studies of their olfactory microcircuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Determinants of human olfactory performance: a cross-cultural study.

PubMed

Sorokowska, Agnieszka; Sorokowski, Piotr; Frackowiak, Tomasz

2015-02-15

Olfaction allows us to detect subtle changes in our environment, but sensitivity of the sense of smell varies among individuals. Although a significant number of research papers discuss the relationship between olfactory abilities and environmental factors, most studies have been conducted on Western populations or in developed Asian societies. The potential environmental and cultural determinants of olfactory acuity warrant further exploration. In the current study, we compared previously published data on olfaction in an industrialized, modern society (i.e., Europeans) and an indigenous society living in unpolluted, natural environmental conditions (i.e., Tsimane'), with novel data on the olfactory acuity of inhabitants of the Cook Islands. Like the European population (and contrary to the Tsimane'), the Cook Islands people form a modern society, and like the Tsimane' population (and contrary to the Europeans), they live in an unpolluted region. Thus, these comparisons enabled us to independently assess the importance of both air pollution and changes in lifestyle for olfactory abilities in modern societies. Our results indicate that people from the Cook Islands had significantly higher olfactory acuity (i.e., lower thresholds of odor detection) than did Europeans and Tsimane' people. Interestingly, the olfactory sensitivity of Europeans was significantly lower than the olfactory sensitivity of the remaining two groups. Our data suggest that air pollution is an important factor in the deterioration of the sense of smell. However, it is also possible that factors such as agricultural and/or cooking practices, alcohol consumption, and access to medical service may also influence olfactory acuity. Copyright © 2014 Elsevier B.V. All rights reserved.

Unraveling Cajal's view of the olfactory system

PubMed Central

Figueres-Oñate, María; Gutiérrez, Yolanda; López-Mascaraque, Laura

2014-01-01

The olfactory system has a highly regular organization of interconnected synaptic circuits from the periphery. It is therefore an excellent model for understanding general principles about how the brain processes information. Cajal revealed the basic cell types and their interconnections at the end of the XIX century. Since his original descriptions, the observation and analysis of the olfactory system and its components represents a major topic in neuroscience studies, providing important insights into the neural mechanisms. In this review, we will highlight the importance of Cajal contributions and his legacy to the actual knowledge of the olfactory system. PMID:25071462

Expressional and functional interactions of two Apis cerana cerana olfactory receptors.

PubMed

Guo, Lina; Zhao, Huiting; Jiang, Yusuo

2018-01-01

Apis cerana cerana relies on its sensitive olfactory system to perform foraging activities in the surrounding environment. Olfactory receptors (ORs) are a primary requirement for odorant recognition and coding. However, the molecular recognition of volatile compounds with ORs in A. cerana cerana is still not clear. Hence, in the present study, we achieved transient transfection and cell surface expression of A. cerana cerana ORs (AcerOr1 and AcerOr2; AcerOr2 is orthologous to the co-receptor) in Spodoptera frugiperda (Sf9) cells. AcerOr2 narrowly responded to N-(4-ethylphenyl)-2-((4-ethyl-5-(3-pyridinyl)-4H-1,2,4-triazol-3-yl) thio) acetamide (VUAA1), whereas AcerOr1 was sensitive to eugenol, lauric acid, ocimene, 1-nonanol, linolenic acid, hexyl acetate, undecanoic acid, 1-octyl alcohol, and nerol. Of the compounds tested, AcerOr1 showed the highest sensitivity to these odorants with EC 50 values of 10 -7 and 10 -8 M, and AcerOr2 recognized VUAA1 with higher sensitivity [EC 50 = (6.621 ± 0.26) × 10 -8 ]. These results indicate that AcerOr2 is an essential gene for olfactory signaling, and AcerOr1 is a broadly tuned receptor. We discovered ligands that were useful for probing receptor activity during odor stimulation and validated three of them by electroantennography. The response increased with concentration of the odorant. The present study provides insight into the mechanism of olfactory discrimination in A. cerana cerana .

The olfactory gonadotropin-releasing hormone immunoreactive system in mouse.

PubMed

Jennes, L

1986-10-29

The olfactory gonadotropin-releasing hormone (GnRH) system in mice was studied with immunofluorescence in combination with lesions of the olfactory bulb and retrograde transport of horseradish peroxidase (HRP) which was administered intravascularly, intranasally or into the subarachnoid space. GnRH-positive neurons were located in the two major branches forming the septal roots of the nervus terminalis, in the ganglion terminale, within the fascicles of the nervus terminalis throughout its extent, in a conspicuous band which connects the ventral neck of the caudal olfactory bulb with the accessory olfactory bulb and in the nasal mucosa. GnRH-positive fibers were seen in all areas in which neurons were found, i.e. in the rostral septum, the ganglion and nervus terminalis and in the nasal subepithelium. In addition, a broad bundle of fibers was observed to surround the entire caudal olfactory bulb, connecting the rostral sulcus rhinalis with the ventrocaudal olfactory bulb. Fibers were seen in close association with the main and accessory olfactory bulb, with the fila olfactoria and with the nasal mucosa. Throughout the olfactory bulb and the nasal epithelium, an association of GnRH fibers with blood vessels was apparent. Intravascular and intranasal injection of HRP resulted in labeling of certain GnRH neurons in the septal roots of the nervus terminalis, the ganglion terminale, the nervus terminalis, the caudal ventrodorsal connection and in the accessory olfactory bulb. After placement of HRP into the subarachnoid space dorsal to the accessory olfactory bulb, about 50% of the GnRH neurons in the accessory olfactory bulb and in the ventrodorsal connection were labeled with HRP. Also, a few GnRH neurons in the rostral septum, the ganglion terminale and in the fascicles of the nervus terminalis had taken up the enzyme. Lesions of the nervus terminalis caudal to the ganglion terminale resulted in sprouting of GnRH fibers at both sites of the knife cut. Lesions rostral

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R