Effects of unilateral olfactory deprivation in the developing opossum, Monodelphis domestica

Unilateral naris closure in young rodents leads to striking alterations in the development of the ipsilateral olfactory system. One of the most pronounced effects is a 25% reduction in the size of the experimental olfactory bulb, a change that stems in part from decreased cell survival. Since naris occlusion in rodents alters the system more during development than in adulthood, we investigated the consequences of olfactory deprivation in a species that is born in a very immature state, Monodelphis domestica. In this pouchless marsupial, offspring are born after a short 14-day gestation. In the present study, the thymidine analogue bromodeoxyuridine was used to examine early postnatal neurogenesis in the olfactory bulb. Unlike rats and mice, neurogenesis of the main output neurons (the mitral cells) continues into postnatal life. Unilateral naris closure was begun on postnatal day 4 (P4) or P5 in Monodelphis and continued for 30 or 60 days. Laminar volume measurements revealed a significant reduction in the size of the experimental bulb following 60, but not 30, days of early olfactory deprivation. Mitral cell number estimates indicated a significant reduction after both 30 and 60 days of naris closure. The immaturity of Monodelphis offspring may render the population of mitral cells susceptible to the effects of olfactory deprivation. These findings suggest that afferent activity plays a role in the survival of all bulb neurons, irrespective of cell class.     

Electrophysiological characterization of chemosensory neurons from the mouse vomeronasal organ

The mechanism of sensory transduction in chemosensory neurons of the vomeronasal organ (VNO) is not known. Based on molecular data, it is likely to be different from that mediating sensory transduction in the main olfactory system. To begin to understand this system, we have characterized the electrophysiological properties of dissociated mouse VNO neurons with patch-clamp recording. Sensory neurons were distinguished from nonsensory neurons by the presence of a dendrite, by immunoreactivity for olfactory marker protein, and by the firing of action potentials. The resting potential of VNO neurons was approximately -60 mV, and the average input resistance was 3 Gomega. Current injections as small as 1-2 pA elicited steady trains of action potentials that showed no sign of elicited steady trains of action potentials that showed no sign of adaptation during a 2 sec stimulus duration. The voltage-gated conductances in VNO neurons are distinct from those in olfactory neurons. The Na+ current is composed of two components; the major component was TTX-sensitive (Ki = 3.6 nM). The outward K+ current activates at -30 mV with kinetics 10 times slower than for K+ currents in olfactory neurons. The Ca2+ current is composed of at least two components: an L-type current and a T-type current that activates at -60 mV and is not found in olfactory neurons. We find no evidence for cyclic nucleotide-gated channels in VNO neurons under a variety of experimental conditions, including those that produced large responses in mouse olfactory neurons, which is further evidence for a novel transduction pathway.     

Glycobiology of the olfactory system

The olfactory system is a highly plastic region of the nervous system. Continuous remodeling of neuronal circuits in the olfactory bulb takes place throughout life as a result of constant turnover of primary sensory olfactory neurons in the periphery. Glycoconjugates are very important in olfactory development, regeneration and function. This article deals with different aspects of glycobiology relevant for the olfactory system. Various anatomical, developmental and functional subdivisions of the olfactory system have been labeled with exogenous lectins. The application of reverse lectin histochemistry resulted in the visualization of endogenous lectins, involved in fasciculation of olfactory axons. Numerous glycoproteins, among them members of the immunoglobulin superfamily, the cadherins and integrins as well as different glycolipids and proteoglycans can act as surface adhesion molecules in the olfactory system. The olfactory-specific form of the sialoglycoprotein neural cell adhesion molecule is implicated in olfactory neuronal and axonal guidance. Glycoconjugates including laminin, fibronectin and proteoglycans are abundant components of the olfactory extracellular matrix, influencing neurite outgrowth and cellular migration. Immunohistochemical labeling has revealed occurrence of the carbohydrate differentiation antigen, playing a role in neurulation and morphogenesis of the very early olfactory system. The synaptic vesicle glycoprotein, appearing also early in olfactory development, is used as a marker of olfactory tumors. Finally, membrane and transmembrane glycoconjugates as well as secreted glycoconjugates may act as olfactory receptor molecules.     

Autosomal recessive cornea plana. A clinical and genetic study of 78 cases in Finland

Occupational exposure to nickel by inhalation may result in impaired olfactory sense. Recent studies have shown that nickel is transported from the olfactory epithelium along the axons of the primary olfactory neurons to the brain. In the present study 63Ni2+ was applied in the olfactory chambers of pikes (Esox lucius) and the rate at which the metal was transported in the primary olfactory neurons was determined by beta-spectrometry. The results showed a wave of 63Ni2+ in the olfactory nerves, which slowly moved toward the olfactory bulbs. The maximal 63Ni2+ transport rate corresponding to the movement of the base of the wave front was found to be about 0.13 mm/h at the experimental temperature (10 degrees C). This rate of 63Ni2+ transport falls into the class of slow axonal transport. Radioluminography of tape sections of a pike given 63Ni2+ in the right olfactory chamber showed a selective labeling of the right olfactory nerve. The subcellular distribution of 63Ni2+ in the olfactory nerves and the olfactory epithelium of the pikes was studied in tissues subjected to homogenizations and centrifugations, and these methods were also used to examine the subcellular distribution of 63Ni2+ in tissues of the olfactory system of rats given the metal intranasally. It was found that the 63Ni2+, in both the pike and the rat, was present in the cytosol and also in association with various particulate cell constituents. Gel filtrations of the cytosols showed that the 63Ni2+ mainly was eluted at a Ve/Vo ratio corresponding to a MW of about 250. The same coefficient was obtained in gel filtrations performed with 63Ni2+ mixed with histidine in vitro. It is likely that the cytosolic nickel may be bound to histidine or possibly to other amino acids which are similar in size to histidine. Additionally, in the olfactory tissues of the rat the 63Ni2+ was partly present in the cytosol in association with a component with a MW of about 25,000. It is concluded that (i) 63Ni2+ is transported in the primary olfactory neurons by means of slow axonal transport, (ii) in this process the metal is bound to both particulate and soluble cytosolic constituents, and (iii) the metal shows this subcellular distribution also in other parts of the olfactory system.     

The ultrastructure of an olfactory sensillum on the maxillary palps of locusta migratoria (L.)

The olfactory sensilla on the maxillary palp tip of Locusta migratoria (L.) resemble the surrounding contact chemoreceptors in general morphology. The perforated peg has a thicker wall than is commonly found in olfactory sensilla. The form and position of the sensilla are considered in relation of the olfactory function. The fine structure of the dendrites is discussed in relation to that described in other olfactory sensilla.     

Head-portion exposure to low-level X-rays reduces isolation-induced aggression of mouse, and involvement of the olfactory carnosine in modulation of the radiation effects

Social isolation has been widely described to induce a compulsive aggressive behavior. The aggressiveness due to isolation in mice has often been used as a means for the better understanding of disturbed behavior in human beings. In the course of a study of the behavioral effects, we have noticed that fighting injuries, usually observed among male ICR mice, tend to decrease in mice irradiated with low-dose X-rays. We, therefore, quantitatively examined the effects of low-dose X-irradiation on aggressive behavior using a resident-intruder paradigm in which a resident mouse attacks an intruder that entered its territory. Male ICR white Swiss mice became gradually calm, and showed remarkably quiet behavior 7-10 days after whole-head 5 or 15 cGy X-irradiation. Only exposure of the anterior part of the head (olfactory system including orbits) also induced the remarkable suppression of the aggressive behavior. The olfactory system has direct access to the limbic system, a central part of the brain concerned with emotion. The calm behavior induced by low-dose X-irradiation might be related to the changes in the olfactory function. We also obtained data on brain biochemistry giving further support for the above low-dose effects on mouse behavior. The carnosine content and its synthetase activity in the olfactory bulbs decreased significantly after only the anterior part of the head had been exposed. Higher doses (25-35 cGy), however, did not induce such effects. The results suggest that the depression of aggressive behavior is limited to animals irradiated with the smaller doses.     

Sensitivity reaction to parenteral vitamin B12: recurrence of symptoms after Marmite ingestion

No other successful nuclear method, besides bone scanning, has been reported in the literature for in vivo imaging of olfactory neuroblastoma. In this article, excellent uptake is reported by an In-111 labeled bleomycin complex (BLMC) in the ethmoid region of a histologically confirmed olfactory neuroblastoma. The uptake of BLMC was 0.7 x 10(-3)% ID/g at 48 hours after injection, and tumor-to-muscle and tumor-to-fat ratios were 6:1 and 11:1, respectively. The authors conclude that BLMC should be considered as a useful imaging agent, and the BLMC has potential as a radiochemotherapeutic agent against an olfactory neuroblastoma.     

Olfactory bulb habituation to odor stimuli.

Habituation is a simple form of memory, yet its neurobiological mechanisms are only beginning to be understood in mammals. In the olfactory system, the neural correlates of habituation at a fast experimental timescale involving very short intertrial intervals (tens of seconds) have been shown to depend on synaptic adaptation in olfactory cortex. In contrast, behavioral habituation to odorants on a longer timescale with intertrial intervals of several minutes depends on processes in the olfactory bulb, as demonstrated by pharmacological studies. We here show that behavioral habituation to odorants on this longer timescale has a neuronal activity correlate in the olfactory bulb. Spiking responses of mitral cells in the rat olfactory bulb adapt to, and recover from, repeated odorant stimulation with 5-min intertrial intervals with a time course similar to that of behavioral habituation. Moreover, both the behavioral and neuronal effects of odor habituation require functioning N-methyl-d-aspartic acid receptors in the olfactory bulb. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Subfamily of olfactory receptors characterized by unique structural features and expression patterns

The complex chemospecificity of the olfactory system is probably due to the large family of short-looped, heptahelical receptor proteins expressed in neurons widely distributed throughout one of the several zones within the nasal neuroepithelium. In this study, a subfamily of olfactory receptors has been identified that is characterized by distinct structural features as well as a unique expression pattern. Members of this receptor family are found in mammals, such as rodents and opossum, but not in lower vertebrates. All identified subtypes comprise an extended third extracellular loop that exhibits amphiphilic properties and contains numerous charged amino acids in conserved positions. Olfactory sensory neurons expressing these receptor types are segregated in small clusters on the tip of central turbinates, thus representing a novel pattern of expression for olfactory receptors. In mouse, genes encoding the new subfamily of receptors were found to be harbored within a small contiguous segment of genomic DNA. Based on species specificity as well as the unique structural properties and expression pattern, it is conceivable that the novel receptor subfamily may serve a special function in the olfactory system of mammals.     

Magnetic resonance imaging of the olfactory apparatus

The magnetic resonance imaging visualization of the olfactory apparatus is reported in this article. We used a superconductor-type magnetic resonance device (Siemens Magnetom H15 (1.5 T) with a surface coil. The subjects were patients with posttraumatic anosmia. The olfactory bulbs were clearly visualized in the frontal plane magnetic resonance images, the olfactory bulbs and the foramina of the cribriform plate were visualized in the sagittal section, and the olfactory bulbs, tracts, and other structures were visualized in the coronal sections. The olfactory nerves could not be seen.     

The nitric oxide-cGMP pathway may mediate communication between sensory afferents and projection neurons in the antennal lobe of Manduca sexta

The nitric oxide (NO)-cGMP signaling system is thought to play important roles in the function of the olfactory system in both vertebrates and invertebrates. One way of studying the role of NO in the nervous system is to study the distribution and properties of NO synthase (NOS), as well as the soluble guanylyl cyclases (sGCs), which are the best characterized targets of NO. We study NOS and sGC in the relatively simple and well characterized insect olfactory system of the hawkmoth, Manduca sexta. We have cloned Manduca sexta nitric oxide synthase (MsNOS) and two sGCs (MsGCalpha1 and MsGCbeta1), characterized their basic biochemical properties, and studied their expression in the olfactory system. The sequences of the Manduca genes are highly similar to their mammalian homologs and show similar biochemical properties when expressed in COS-7 cells. In particular, we find that MsGC functions as an obligate heterodimer that is stimulated significantly by NO. We also find that MsNOS has a Ca2+-sensitive NO-producing activity similar to that of mammalian neuronal NOS. Northern and in situ hybridization analyses show that MsNOS and the MsGCs are expressed in a complementary pattern, with MsNOS expressed at high levels in the antennae and the MsGCs expressed at high levels in a subset of antennal lobe neurons. The expression patterns of these genes suggest that the NO-sGC signaling system may play a role in mediating communication between olfactory receptor neurons and projection neurons in the glomeruli of the antennal lobe.     

Spatiotemporal patterns of expression of extracellular matrix molecules in the developing and adult rat olfactory system

Using immunocytochemical methods, we have examined extensively the spatial and temporal patterns of expression of three extracellular matrix molecules-laminin, fibronectin, and type IV collagen-in the embryonic, postnatal (days 2 and 11) and adult rat olfactory system. The study started at embryonic day 14 when olfactory fibres and their associated migrating cells course through the nasal mesenchyme. From embryonic day 14 to the adult, a sheet-like pattern of labelling for laminin, fibronectin and type IV collagen was observed along the basal surface of the olfactory epithelium and around the telencephalon. This type of labelling was continuous around the telencephalic vesicle, whereas it appeared disrupted in the basal lamina of the olfactory epithelium to permit exit of the olfactory axons and their associated migrating cells into the mesenchyme. From embryonic day 14 to day 20, punctate labelling for the three molecules studied was observed along the mesenchymal olfactory pathway, the ventral part of the olfactory bulb, the olfactory nerve layer and the presumptive glomerular layer, respectively. By embryonic day 17, the punctate labelling initially detected in the mesenchymal olfactory pathway was replaced by a sheet-like pattern related to the mature basal lamina surrounding the olfactory axon fascicles. Punctate labelling for laminin and type IV collagen persisted in the olfactory nerve layer and around the glomeruli through adult life whereas that of fibronectin declined and disappeared by postnatal day 2. The spatiotemporal distribution of the punctate pattern for laminin, fibronectin and type IV collagen observed in the embryonic olfactory system suggests a role in delineating the pathway for olfactory axon elongation. The continuous expression of laminin and type IV collagen in the adult olfactory bulb may be related to the regenerative activity and high plasticity of the olfactory system.     

Isolation and characterization of rat olfactory marker protein

The olfactory marker protein was isolated and characterized from rat olfactory bulbs. Its properties and those of the olfactory marker protein isolated from the mouse are described. The rat protein was less acidic (pI = 5.0) than the mouse protein (pI = 4.7). However, the amino acid compositions were very similar: in both proteins arginine plus lysine accounted for 13 mol% and glutamate plus aspartate for 30 mol% of the total residues. Molecular weights of both proteins estimated by sodium dodecyl sulfate gel electrophoresis were indistinguishable and estimated to be 16,500. The molecular weight of the native rat olfactory marker protein estimated by gel filtration techniques was 30,000, which is identical to the molecular weight of the native mouse and garfish olfactory marker proteins. This suggested a dimeric structure. The purified rat and mouse proteins behaved like species of 35,000 molecular weight on gel filtration.     

Atypical olfactory glomeruli subset of the rat: quantitative study and organization of the peripheral afferents

The atypical glomeruli constitute a particular subset of olfactory glomeruli in the rat olfactory bulb which is mainly characterized by a strong centrifugal cholinergic innervation. In the present study, the topographical organization of the mucoso-bulbar projection of these glomeruli was analysed using small injections of WGA-HRP into the anterior nasal cavity of adult rats. The atypical olfactory glomeruli were visualized on adjacent bulbar sections using acetylcholinesterase histochemistry. A mean of 29 atypical glomeruli per bulb was observed in several areas of the posterior half of the olfactory bulb. Following the rostro-caudal axis of the olfactory bulb, the first atypical glomeruli were located in lateral positions, then in dorsal and ventral ones. The most posterior atypical glomeruli were located in the bulbar medial side. Concerning the projections from the periphery to the atypical glomeruli, various WGA-HRP patterns of labelling were observed. When the surface area of injection sites in the anterior part of the olfactory sheet was between 30 and 40 mm2, half of the atypical population was labelled with the atypical glomeruli being heavily labelled. All sites of distribution previously described were represented. When the surface area of injection sites was inferior to 20 mm2, only some positions distributed along the bulbar antero-posterior axis were represented. These atypical glomeruli were generally partially labelled. Taken together, these results suggest that, although atypical glomeruli are restricted in the posterior olfactory bulb, they receive peripheral projections diffusely organized along the antero-posterior axis of the olfactory mucosa. This profile was compared with that of other classical olfactory glomeruli.     

Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis

An understanding of the olfactory system of any animal must account for how odor mixtures are perceived and processed. The present experiments apply associationist models to the study of how elements are processed in binary odorant mixtures. Using experimental designs for Proboscis Extension Conditioning of honey bees, I show that learning about a pure odorant element is frequently affected by its occurrence in a mixture with a second odorant. Presence of a background odor when an odorant is associated with sucrose reinforcement decreases the rate and/or asymptotic level of associative strength that accumulates to that odorant. This interaction is in part due to synthetic qualities that arise in sensory transduction and initial processing. In addition, it involves an attention-like processing system like that involved in overshadowing. Therefore, a model that includes representations of the component and configural qualities of odorants in mixtures is needed to provide a more complete account of learning about odor mixtures.     

Three-Dimensional Digital Representation of Granular Material Microstructure from X-Ray Tomography Imaging

This paper presents the use of x-ray tomography imaging to reconstruct a three-dimensional (3D) digital representation of individual particles in a granular system. The granular system is represented by the mass center coordinates and the morphology representation of each particle. An automated procedure using pattern recognition to identify related particle cross sections in adjacent serial images was developed. Procedures to calculate quantities needed for subsequent simulation of particle behavior including the volume and the momentum of inertia of each particle are also presented. The developments described in the paper enable modeling and simulation of the behavior, and experimental observations of the particle kinematics of real microstructures of granular materials in a true 3D platform.     

Olfactory bulbectomy induces reproductive recrudescence in golden hamsters on short photoperiod

Olfactory bulbectomy results in a marked increase in gonadotropin secretion and prevents the reproductive regression associated with short photoperiod when the olfactory bulbectomy is done before exposure to the inhibitory photoperiod. The present study tested whether olfactory bulbectomy would offset the influence of short photoperiod if done after the reproductive system had regressed. Adult golden hamsters Mesocricetus auratus were divided into four groups: early sham (surgery at week-4); early olfactory bulbectomy (surgery at week-4); late sham (surgery at week 14) and late olfactory bulbectomy (surgery at week 14). At t = 0, all golden hamsters were placed in a short photoperiod (L:D 10:14). Early olfactory bulbectomy prevented testicular regression; the late olfactory bulbectomy group recrudesced much earlier than the sham groups. These results indicate that the tonic inhibitory influence of the olfactory bulbs is required for initiation of short photoperiod induced testicular regression and is also essential for the maintenance of the regressed state.     

Beta-galactosidase-labelled relay neurons of homotopic olfactory bulb transplants establish proper afferent and efferent synaptic connections with host neurons

The vertebrate olfactory system has long been an attractive model for studying neuronal regeneration and adaptive plasticity due to the continuous neurogenesis and synaptic remodelling throughout adult life in primary and secondary olfactory centres, its precisely ordered synaptic network and accessibility for manipulation. After homotopic transplantation of fetal olfactory bulbs in bulbectomized neonatal rodents, newly regenerated olfactory neurons form glomeruli within the graft, and the efferent mitral/tufted cells of the transplant innervate the host brain, terminating in higher olfactory centres. However, the synaptic connections of the transplanted relay neurons within the graft and/or host's olfactory centres could not be characterized mainly because of lack of suitable cell-specific markers for these neurons. In this study, we have used olfactory bulbs from transgenic fetuses, in which the majority of the mitral/tufted cells express the bacterial enzyme beta-galactosidase, for homotopic olfactory bulb transplantation following complete unilateral bulbectomy. In the transplants, the cell bodies and terminals of the donor mitral/tufted cells were identified by beta-galactosidase histochemistry and immunocytochemistry at both light and electron microscope levels. We demonstrate that transplanted relay neurons re-establish specific synaptic connections with host neurons of the periphery, source of the primary signal and central nervous system, thereby providing the basis for a functional recovery in the lesioned olfactory system.     

Posttraumatic olfactory dysfunction: MR and clinical evaluation

PURPOSE: To evaluate the sites of injury in patients with posttraumatic olfactory deficits and to compare damage with findings on clinical olfactory tests. METHODS: Twenty-five patients with posttraumatic olfactory dysfunction were examined by means of olfactory testing, endoscopy, and MR imaging. MR surface-coil scans through the olfactory bulbs and tracts and head-coil scans of the temporal lobes were evaluated. Quantitative and qualitative gradings of damage to the olfactory bulbs, tracts, subfrontal region, hippocampus, and temporal lobes were compared with results on tests of odor identification, detection, memory, and discrimination. RESULTS: Twelve patients were anosmic, eight had severe impairment, and five were mildly impaired. Injuries to the olfactory bulbs and tracts (88% of patients), subfrontal region (60%), and temporal lobes (32%) were found, but these did not correlate well with individual olfactory test scores. Volumetric analysis showed that patients without smell function had greater volume loss in olfactory bulbs and tracts than did those posttraumatic patients who retained some sense of smell. Qualitative and quantitative assessments of damage showed few significant correlations with olfactory tests, probably because of multifocal injuries, primary olfactory nerve damage, and the constraints of a small sample size on the detection of clinically significant differences. CONCLUSION: MR imaging shows abnormalities in patients with posttraumatic olfactory dysfunction at a very high rate (88%), predominantly in the olfactory bulbs and tracts and the inferior frontal lobes.     

Enzyme determination in vitro of inhibitor activity of beta-lactamase from tazobactam. Comparison with high performance liquid chromatography

Most physiological studies of the human olfactory system have concentrated on the cortical level; the olfactory bulbar level has been studied rarely. We attempted to stimulate the human olfactory mucosa by electrical pulse to detect the bulbar potentials. Electrical stimulation (2 mA, 0.5 ms) of the human olfactory mucosa evoked a change in potential recorded from the frontal sector of the head. A negative peak of the evoked potential that occurred at 19.4 ms (grand means, n = 5) after stimulation was the clearest. The highest amplitude of the potential was recorded from the frontal sector of the head on the stimulated side. Our findings were similar to the experimental results obtained from the olfactory bulbs of animals. This evoked potential was considered to be the human olfactory bulbar potential. When the subjects were stimulated by applying electricity to the olfactory mucosa, no sensation of smell occurred even though evoked potentials were recorded. Evoked potentials were recorded only when the stimulating electrode was located in the olfactory cleft. When the stimulating electrode was outside the olfactory cleft, the stimulation caused pain. The trigeminal nerve seemed to be stimulated by electricity. Olfactory evoked potentials produced by the electrical stimulation of the human olfactory mucosa should aid the research on human olfactory physiology, and may be applicable to clinical tests of olfactory dysfunction.