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PubMed2000

The smell of burnt toast: a case report.

A 71-year-old woman awoke one morning to find that she perceived all aromas, odors, and fragrances as smelling like burnt toast. Over the next three years, numerous studies and therapeutic trials failed to elicit the cause of her dysosmia or to provide relief. Finally, the demonstration of small infarcts as seen on a brain MRI suggested that an infarct near the olfactory pathway was responsible for the sudden onset and the 11 year persistence of her unique paromia.

Aged↗
PubMed1997

Spread of measles virus through axonal pathways into limbic structures in the brain of TAP1 -/- mice.

The spread of measles virus into the brain was studied exploiting the olfactory pathway, which represents an important route of neuroinvasion by viruses. The virus was injected into the main olfactory bulb of wild-type mice and mice with disrupted TAP1 gene (TAP refers to the Transporter associated with Antigen Presentation), which codes for products essential for the cell-mediated immune response. Virus invasion was monitored for 4 weeks by immunohistochemistry. The distribution of measles virus was found to be restricted to brain areas connected with the olfactory bulbs. However, in the wild-type mice there was a marked infiltration of lymphocytes in the infected brain structures, and the virus did not pass beyond the piriform cortex. In the TAP1 -/- mice the virus spread more extensively along olfactory projections into the limbic system and monoaminergic brainstem neurons. Infected mice of both types developed seizures, which may have been focally evoked from the piriform cortex. This study provides evidence that measles virus can spread through axonal pathways in the brain. The findings obtained in the gene-manipulated mice point out that a compromised immune state of the host may potentiate targeting of virus to the limbic system through olfactory projections.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Distribution of nimodipine in brain following intranasal administration in rats.

AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS: Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively. The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

Administration, Intranasal↗
PubMed1995

Electron microscopic study of synaptogenesis and myelination of the olfactory centers in developing rats.

Development of the central olfactory system was studied in the rat with an electron microscope at three main structures: the olfactory bulb, the lateral olfactory tract, and the primary olfactory cortex (the piriform cortex). As a parameter of development, the synaptic density was examined quantitatively in the bulbar glomerulus and layer Ia (termination of bulbofugal fibers) of the piriform cortex. which are the key stations of the olfactory pathway. The synaptic densities in the glomerulus and those in layer Ia were 5.7% and 4.6% on embryonic day 19, 15.8% and 12.5% on postnatal day (P) 0, and 57.3% and 37.2% on P10, as compared with the adult (100%). As another parameter of development, the density of myelinated axons in the lateral olfactory tract was examined quantitatively. The densities of myelinated axons in the tract were 0% on P5, 15.1% on P10, and 73.5% on P21 of the adult density. Maturation in the tract was still progressing, even at P21, in terms of bundle formation and the thickness of myelin sheaths. The results show that synaptogenesis in the bulbar glomerulus is followed by synaptogenesis in layer Ia of the piriform cortex, and that myelination in the lateral olfactory tract occurs over a prolonged period, even in the stages after P21.

Aging↗
PubMed1988

Electron microscopic immunocytochemical localization of nerve growth factor in developing mouse olfactory neurons.

The immunocytochemical localization of nerve growth factor (NGF) in the embryonic mouse has been examined using correlative light and electron microscope procedures. In flat-embedded thick sections, primary sensory neurons of the olfactory pathway were clearly visible by their high level of NGF-like immunoreactivity. When ultrathin sections were examined under the electron microscope, the HRP reaction product present in the nasal epithelium was confined to the cytoplasm of the chemoreceptor cells, including the dendrites projecting into the nasal cavity. The axons projecting to the olfactory bulb and axon bundles within the bulb were also stained specifically for NGF. The reaction product did not appear to be associated with any particular subcellular structure. Neither the columnar supporting cells nor the basal precursor cells showed any evidence of immunoreactivity. No evidence was found for the presence of NGF in cells such as epithelial or glial cells within the immediate environment of the receptor neurons. These first subcellular localization studies indicate the presence of high levels of NGF in neurons not known to be sensitive to the trophic molecule.

Animals↗
PubMed2005

Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones.

It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high-resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2-Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed.

Animals↗
PubMed1999

Characterizing complex chemosensors: information-theoretic analysis of olfactory systems.

The mechanisms that underlie a wine lover's ability to identify a favorite vintage and a dog's ability to track the scent of a lost child are still deep mysteries. Our understanding of these olfactory phenomena is confounded by the difficulty encountered when attempting to identify the parameters that define odor stimuli, by the broad tuning and variability of neurons in the olfactory pathway,and by the distributed nature of olfactory encoding. These issues pertain to both biological systems and to newly developed 'artificial noses' that seek to mimic these natural processes. Information theory, which quantifies explicitly the extent to which the state of one system (for example, the universe of all odors) relates to the state of another (for example, the responses of an odor-sensing device),can serve as a basis for analysing both natural and engineered odor sensors. This analytical approach can be used to explore the problems of defining stimulus dimensions, assessing strategies of neuronal processing, and examining the properties of biological systems that emerge from interactions among their complex components. It can also serve to optimize the design of artificial olfactory devices for a variety of applications, which include process control, medical diagnostics and the detection of explosives.

Animals↗
PubMed2003

Mesenchymal/epithelial regulation of retinoic acid signaling in the olfactory placode.

We asked whether mesenchymal/epithelial (M/E) interactions regulate retinoic acid (RA) signaling in the olfactory placode and whether this regulation is similar to that at other sites of induction, including the limbs, branchial arches, and heart. RA is produced by the mesenchyme at all sites, and subsets of mesenchymal cells express the RA synthetic enzyme RALDH2, independent of M/E interactions. In the placode, RA-producing mesenchyme is further distinguished by its coincidence with a molecularly distinct population of neural crest-associated cells. At all sites, expression of additional RA signaling molecules (RARalpha, RARbeta, RXR, CRABP1) depends on M/E interactions. Of these molecules, RA regulates only RARbeta, and this regulation depends on M/E interaction. Expression of Fgf8, shh, and Bmp4, all of which are thought to influence RA signaling, is also regulated by M/E interactions independent of RA at all sites. Despite these common features, RALDH3 expression is distinct in the placode, as is regulation of RARbeta and RALDH2 by Fgf8. Thus, M/E interactions regulate expression of RA receptors and cofactors in the olfactory placode and other inductive sites. Some aspects of regulation in the placode are distinct, perhaps reflecting unique roles for additional local signals in neuronal differentiation in the developing olfactory pathway.

Aldehyde Oxidoreductases↗
PubMed2005

The olfactory organ modulates gonadotropin-releasing hormone types and nest-building behavior in the tilapia Oreochromis niloticus.

Direct olfactory inputs to any of the known gonadotropin-releasing hormone (GnRH) containing neurons have not been demonstrated. Therefore, the rationale of this study was to examine whether olfactory inputs might in some way interact with the GnRH system(s) to synchronize reproductive behaviors. In order to establish this, we used anosmic mature male tilapia to investigate changes in reproductive behaviors, gonadal morphology, and GnRH1, GnRH2, and GnRH3 cellular morphology and change in GnRH mRNA levels by real-time polymerase chain reaction. Bilateral removal of the olfactory rosettes followed by occlusion of the nasal cavity (ORX) inhibited nest-building behavior, but had no effect on aggressive and sexual behaviors or gonadal morphology. ORX failed to alter the morphological features of GnRH1, GnRH2, and GnRH3 (cell number, size, GnRH optical density), but significantly decreased copies of GnRH1 and GnRH2 mRNAs. GnRH immunoreactive fibers were not evident in the olfactory nerve and rosettes. DiI application to the olfactory nerve labeled inputs primarily to the glomerular layer of the olfactory bulbs and extrabulbar inputs to the forebrain but not to GnRH neurons. These results provide evidence that the olfactory rosette is crucial for modulating nest-building behavior through second-order olfactory pathways interacting with GnRH1 and GnRH2 neuronal systems.

Aggression↗
PubMed2006

Accessory olfactory neural Fos responses to a conditioned environment are blocked in male mice by vomeronasal organ removal.

The ability of an anesthetized estrous female to induce a conditioned place preference (CPP) response was assessed in male mice from which the vomeronasal organ (VNO) had either been removed (VNOx) or left intact (VNOi) in an initial effort to assess the possible contribution of VNO-accessory olfactory inputs to the intrinsically rewarding properties of opposite-sex body odorants. Both VNOi and VNOx male mice acquired a CPP after repeated pairing of an initially non-preferred test chamber with an anesthetized estrous female mouse, suggesting that odorants detected by the main olfactory system and/or visual and tactile cues from the anesthetized estrous female can compensate for absent VNO inputs to establish a CPP. Subsequent exposure to this conditioning chamber alone caused significant increases in the number of Fos-immunoreactive cells in the mitral and granule cell layers of the accessory olfactory bulb as well as in the medial amygdala and ventral tegmental area of VNOi but not of VNOx males. These results suggest that activity in distal segments of the VNO-accessory olfactory pathway, in addition to the mesolimbic dopamine reward system, can be conditioned to respond to non-odor cues.

Adaptation, Physiological↗
PubMed2004

The calcium influx pathway in rat olfactory ensheathing cells shows TRPC channel pharmacology.

Pharmacological characterisation of the calcium influx pathway in olfactory ensheathing cells (OECs) was performed using Indo-1 calcium microfluorometry. Our previous work has implicated this pathway in olfactory ensheathing cell support for regeneration of axons from adult CNS neurons. In high extracellular calcium (20 mM), cumulative concentration inhibition curves were generated for Lu(3+), Gd(3+) and econazole, giving IC(50)s of 0.09, 1.51 and 1.13 microM, respectively, and slope values that were not significantly different from unity. Combining these results with those obtained previously, an order of inhibitor potency was found to be Lu(3+)>La(3+)=econazole=Gd(3+)>1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride (SKF96365)>Cd(2+). This profile most closely fits some members of the TRPC family of non-voltage gated calcium influx channels and may indicate that a TRP-mediated calcium influx plays a role in glial-neuronal interaction and axonal regeneration.

Animals↗
PubMed1996

Datura stramonium lectin staining of glial associated extracellular material in insect brains.

To investigate how glial cells structure the neuropile of olfactory pathways in the brains of honeybees and locusts, we used a lectin as a carbohydrate specific molecular label. On frozen sections, Datura stramonium lectin (DSL) stained extracellular material which is mainly associated with glial cells. Preadsorption of the DSL with the carbohydrate N, N'-diacetylchitobiose blocked the staining. The location of glial cells was detected by an antiserum against the glial-specific nuclear repo-protein. Lectin-staining surrounded the neuropile of the antennal lobe, axonal projections of olfactory relay neurons, and the mushroom body neuropile. Within the mushroom body neuropile of the bee, DSL-staining was especially intense at the branching sites of the Kenyon cell axons and in the ventral part of the alpha-lobe. The dissection of the various cellular contributions to the lectin-staining in dissociated cell cultures suggested that certain glial cells, but also neuronal somata of the antennal lobe and Kenyon cells of the mushroom bodies express the label. The expression of lectin-staining matures during the pupal development of the bee, whereas in larval stages of the hemimetabolous locust, the staining pattern appears already completed. Since carbohydrate recognition is thought to play an important role in the formation of neuronal networks, the glial derived extracellular material may contribute to the morphogenesis and structural integrity of the olfactory neuropiles.

Animals↗
PubMed2006

A putative social chemosignal elicits faster cortical responses than perceptually similar odorants.

Social chemosignals, so-called pheromones, have recently attracted much attention in that effects on women's psychophysiology and cortical processing have been reported. We here tested the hypothesis that the human brain would process a putative social chemosignal, the endogenous steroid androstadienone, faster than other odorants with perceptually matched intensity and hedonic characteristics. Chemosensory event-related potentials (ERP) were recorded in healthy women. ERP analyses indicate that androstadienone was processed significantly faster than the control odorants. Androstadienone elicited shorter latencies for all recorded ERP components but most so for the late positivity. This finding indicates that androstadienone is processed differently than other related odorants, suggesting the possibility of a specific neuronal subsystem to the main olfactory pathway akin to the one previously reported in Old-world monkeys and emotional visual stimuli in humans.

Adult↗
PubMed1993

Olfactory deficits in neuroleptic naive patients with schizophrenia.

Because previous studies have shown deficits in olfactory identification for male patients with schizophrenia, either withdrawn from or receiving neuroleptic medication, the purpose of the current study was to determine if such deficits occurred in male patients who had never received neuroleptics. A sample of male (n = 30) and female (n = 10) patients as well as age appropriate controls (males, n = 28, females, n = 30) was assessed in terms of olfactory acuity and identification ability. No differences were found in olfactory acuity, but an olfactory identification deficit was present in 31% of the male patients with schizophrenia. As the olfactory pathways project through the limbic system and to the orbitofrontal cortex, odour identification may be a measure of the functional integrity of these structures. Therefore, these results suggest that for a sub-sample of male patients, the functional integrity of these structures is compromised.

Adult↗
PubMed1997

Distribution of centrifugal neurons targeting the soma clusters of the olfactory midbrain among decapod crustaceans.

To determine the distribution of two systems of centrifugal neurons innervating the soma clusters of the olfactory midbrain across decapod crustaceans, brains of the following nine species comprising most infraorders were immunostained with antibodies against dopamine and the neuropeptides substance P and FMRFamide: Macrobrachium rosenbergii, Homarus americanus, Cherax destructor, Orconectes limosus, Procambarus clarkii, Astacus leptodactylus, Carcinus maenas, Eriocheir sinensis and Pagurus bernhardus. One system consisting of several neurons with dopamine-like immunoreactivity that originate in the eyestalk ganglia was present in the four crayfish but not in any other species. These neurons project mainly into the lateral soma clusters (cluster 10) comprising the somata of ascending olfactory projection neurons and innervate very sparsely the medial soma clusters (clusters 9 and 11) containing the somata of local interneurons. In the innervation pattern of the lateral cluster, the dopamine-immunoreactive neurons showed large species-specific differences. The other system comprises a pair of giant neurons with substance P-like immunoreactivity. These neurons have somata in the median protocerebrum of the central brain and major projections into the lateral clusters and the core of the olfactory lobes, the neuropils that are the first synaptic relay in the central olfactory pathway of decapods; minor arborizations are present in the medial clusters. The system of substance P-immunoreactive giant neurons was present and of great morphological similarity in all studied species. Only in one species, the shrimp Macrobrachium rosenbergii, evidence for co-localization of FMRFamide-like with substance P-like immunoreactivity in these neurons was obtained. These and previously collected data indicate that the centrifugal neurons with dopamine-like immunoreactivity may be associated with the presence of an accessory lobe, a second-order neuropil that receives input from the olfactory lobe and only occurs in spiny lobsters, clawed lobsters and crayfish. The pair of centrifugal giant neurons with substance P-like immunoreactivity, on the other hand, appears to be a constitutive component of the decapod crustacean brain that most likely is functionally associated with the olfactory lobe. Both systems apparently exert modulatory functions on olfactory information processing by preferentially targeting the somata of the projection neurons. Thus, in the olfactory projection neurons, the somata seem to be more directly involved in information processing than in most other neurons of the arthropod CNS.

Animals↗
PubMed2000

Synapse distribution of olfactory interneurons in the procerebrum of the snail Helix aspersa.

The procerebrum is believed to be important for processing olfactory information and storing olfactory memories in terrestrial pulmonate molluscs. Previous results have demonstrated that the procerebral cell population is morphologically heterogeneous. In the present study, serial sections and electron microscopy were used to investigate differences in synapse distributions. The results demonstrate that procerebral neurons with different sites of arborization have distinct patterns of synapse distribution that probably reflect different functional contributions to the olfactory pathway. Cells that have all their arborizations in the procerebrum, but none in the internal mass, have multiple large varicosities that are specialized for output. On the other hand, cells that arborize in the internal mass or outside the procerebrum have mostly input synapses proximal to the soma and mostly output synapses in the terminal region of the neurites. These cells appear to transmit information from the procerebral cell body mass to other central nervous system regions, e.g., the internal mass and the mesocerebrum. The implications of these data are twofold. Firstly, the procerebrum directly participates in distributing processed olfactory information to more central regions of the nervous system. Secondly, the procerebral neuronal population may be divisible into two subgroups: 1) intrinsically arborizing interneurons; and 2) projection neurons. This is significant because the neural organization of the procerebrum may now be compared with that of olfactory systems in other organisms.

Animals↗
PubMed1991

A brain atlas of the northern fulmar (Fulmarus glacialis) in stereotaxic coordinates.

The brain of a procellariiform bird, the Northern Fulmar (Fulmarus glacialis), is presented in the form of a stereotaxic atlas. The Northern Fulmar is especially interesting because both field and laboratory evidence support olfaction as one of its major sensory systems. The nasal cavity and olfactory bulb of most procellariiforms are among the largest of all avian orders; the central olfactory pathways may be more extensive as well. A brain atlas of the Northern Fulmar, a relatively accessible procellariiform species on which several studies have already been done, can provide reference for research both on neural mechanisms underlying olfaction and on comparative neuroanatomical data within Aves and between avian and nonavian groups.

Animals↗
PubMed1983

Olfactory involvement in learning processes.

The purpose of this study is to investigate the existing relations between olfaction and acquisition of the two-way conditioned avoidance response (CAR). For this investigation we have used white adult male Wistar rats. Taking into consideration that several structures of the limbic system participate in learning and memory processes and also that olfactory pathway is believed to have connections with the limbic system, we thought it would be interesting to investigate, if peripheral anosmia influences the performance of rats in the two-way avoidance response. It was shown that peripheral anosmia in rats impaired conditioned avoidance response.

Animals↗