Regeneration of sensory olfactory epithelium and nerves in adult frogs.
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Age-related changes in cell density and the proliferation rate of olfactory ensheathing cells in the lamina propria of postnatal mouse olfactory mucosa.
We investigated age-related changes in the distribution and proliferation of olfactory ensheathing cells (OECs) in postnatal mouse olfactory mucosa. In contrast to reported data on other glial cell types in the peripheral and central nervous systems, OEC cell density in the olfactory nerve bundles in the lamina propria remained almost constant from 10 days through 16 months of age. Electron microscopy of the nerve bundles revealed that axon packing density also was constant during that period. These findings suggest that the ratio of the number of OECs to the unit length of the olfactory neuron axons ensheathed by them does not change markedly throughout the lifetime of mice in an undisturbed condition. By contrast, OEC proliferative density decreased rapidly in the 10-day to 1-month-old period, showing a significant difference, and for the rest of life remained at low level, similar to previous values reported for other glial cell types.
Aging↗
"Imposed" and "inherent" mucosal activity patterns. Their composite representation of olfactory stimuli.
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 for duration. In contrast, the effect of increasing the number of molecules was uniformly positive for all four odorants. However, there was little evidence that these other stimulus variables had a major influence upon the effects of the chromatographic process and regional sensitivity differences in their generation of mucosal activity patterns.
Acyclic Monoterpenes↗
Fatal herpes simplex encephalitis with demonstration of virus in the olfactory pathway.
A fatal case of herpes simplex encephalitis contained viruses within the olfactory pathway but not in the trigeminal ganglia. This finding supports the theory that the olfactory nerves are the portal of entry in adult herpes simplex encephalitis.
Encephalitis↗
Ulex europaeus I and glycine max bind to the human olfactory bulb.
The distribution of binding sites for the fucose-selective lectin Ulex europaeus I and the terminal N-acetylgalactosamine-selective lectin glycine max in the human olfactory bulb were studied. These lectins bound to primary olfactory axons in the olfactory nerve layer and the glomerular layer. They also bound to fibers located in the deeper layers such as the external plexiform layer and the granular layer. Furthermore they projected to the olfactory stalk but not in the cerebrum. The deeper projections of the lectin binding fibers may affect the function of the olfactory bulb in humans.
Aged↗
synaptic organization of the glomerulus in the main olfactory bulb: compartments of the glomerulus and heterogeneity of the periglomerular cells.
According to the combinatorial receptor and glomerular codes for odors, the fine tuning of the output level from each glomerulus is assumed to be important for information processing in the olfactory system, which may be regulated by numerous elements, such as olfactory nerves (ONs), periglomerular (PG) cells, centrifugal nerves and even various interneurons, such as granule cells, making synapses outside the glomeruli. Recently, structural and physiological analyses at the cellular level started to reveal that the neuronal organization of the olfactory bulb may be more complex than previously thought. In the present paper, we describe the following six points of the structural organization of the glomerulus, revealed by confocal laser scanning microscopy and electron microscopy analyses of rats, mice and other mammals: (i) the chemical heterogeneity of PG cells; (ii) compartmental organization of the glomerulus, with each glomerulus consisting of two compartments, the ON zone and the non-ON zone; (iii) the heterogeneity of PG cells in terms of their structural and synaptic features, whereby type 1 PG cells send their intraglomerular dendrites into both the ON and non-ON zones and type 2 PG cells send their intraglomerular dendrites only into the non-ON zone, thus receiving either few synapses from the ON terminals, if present, or none at all; (iv) the spatial relationship of mitral/tufted cell dendritic processes with ON terminals and PG cell dendrites; (v) complex neuronal interactions via chemical synapses and gap junctions in the glomerulus; and (vi) comparative aspects of the organization of the main olfactory bulb.
Animals↗
Expression of SCG10 and stathmin proteins in the rat olfactory system during development and axonal regeneration.
The membrane-associated protein SCG10 is expressed specifically by neuronal cells. Recent experiments have suggested that it promotes neurite outgrowth by increasing microtubule dynamics in growth cones. SCG10 is related to the ubiquitous but neuron-enriched cytosolic protein stathmin. To better understand the role played by SCG10 and stathmin in vivo, we have analyzed the expression and localization of these proteins in both the olfactory epithelium and the olfactory bulb in developing and adult rats, as well as in adult bulbectomized rats. The olfactory epithelium is exceptional in that olfactory receptor neurons constantly regenerate and reinnervate the olfactory bulb throughout animal life-span. SCG10 and stathmin expression in the olfactory receptor neurons was found to be regulated during embryonic and postnatal development and to correlate with neuronal maturation. Whereas SCG10 expression was restricted to immature olfactory receptor neurons (GAP-43-positive, olfactory marker protein-negative), stathmin was also expressed by the basal cells. In the olfactory bulb of postnatal and adult rats, a moderate to strong SCG10 immunoreactivity was present in the olfactory nerve layer, whereas no labeling was detected in the glomerular layer. Olfactory glomeruli also showed no apparent immunoreactivity for several cytoskeletal proteins such as tubulin and microtubule-associated proteins. In unilaterally bulbectomized rats, SCG10 and stathmin were seen to be up-regulated in the regenerating olfactory epithelium at postsurgery stages corresponding to olfactory axon regeneration. Our data strongly suggest that, in vivo, both SCG10 and stathmin may play a role in axonal outgrowth during ontogenesis as well as during axonal regeneration.
Aging↗
[Posturographic registration of body sway after odor stimulation].
The methods of "reflex olfactometry" are rarely able to detect simulated anosmia because of the lack of reproducible correlations between stimulus and intensity of reaction. Interactions between the olfactory and vestibulospinal systems have not yet been investigated. Thirty persons with normosmia and 21 patients with anosmia were studied using a posturographic platform. Only in subjects with normosmia were body sway increases statistically significant in an anterior-posterior direction after the application of an olfactory nerve stimulant. Stimulations of the trigeminal nerve cause both in subjects with normosmia, and anosmia an increase in body sway occurred in a sagittal and lateral direction. The recording of vestibulospinal reactions during platform posturography after application of an olfactory stimulations enables quantification of body sway. These responses can also be useful in differentiating real from stimulated anosmia.
Acetates↗
Ontogenetic expression of spot 35 protein (calbindin-D28k) in human olfactory receptor neurons and its decrease in Alzheimer's disease patients.
Expression of a calcium-binding protein, spot 35 protein (S-35, calbindin-D28k), was investigated immunohistochemically in the human olfactory mucosa of patients who ranged in age from 16 weeks of fetal development to 98 years old, including some with Alzheimer's disease (AD). S-35 immunoreactivity was observed clearly in olfactory receptor neurons (ORNs) and olfactory nerve bundles that were identified previously with antibodies to olfactory marker protein (OMP) and neuron-specific enolase (NSE). Throughout all ages, the mean number of ORNs immunoreactive for OMP did not change significantly, whereas the mean number of NSE- and S-35-immunoreactive ORNs declined markedly in the postnatal infant, young, and old patients when compared with that of the prenatal fetuses. S-35-immunoreactive ORNs decreased significantly in AD patients when compared with AD control patients. These results indicate that ORNs in humans express S-35 and that there is an age-related trend in the expression of S-35. Furthermore, the marked decrease of S-35 expression in ORNs of AD patients suggests that cell excitability associated with calcium ions and cell protective function against overload of intracellular calcium ions decline in these patients.
Adult↗
Relationships between odor-elicited oscillations in the salamander olfactory epithelium and olfactory bulb.
Oscillations in neuronal population activity, or the synchronous neuronal spiking that underlies them, are thought to play a functional role in sensory processing in the CNS. In the olfactory system, stimulus-induced oscillations are observed both in central processing areas and in the peripheral receptor epithelium. To examine the relationship between these peripheral and central oscillations, we recorded local field potentials simultaneously from the olfactory epithelium and olfactory bulb in tiger salamanders (Ambystoma tigrinum). Stimulus-induced oscillations recorded at these two sites were matched in frequency and slowed concurrently over the time course of the response, suggesting that the oscillations share a common source or are modulated together. Both the power and duration of oscillations increased over a range of amyl acetate concentrations from 2.5 x 10(-2) to 1 x 10(-1) dilution of saturated vapor, but peak frequency was not affected. The frequency of the oscillation did vary with different odorant compounds in both olfactory epithelium and bulb (OE and OB): amyl acetate, ethyl fenchol and d-carvone elicited oscillations of significantly different frequencies, and there was no difference in OE and OB oscillation frequencies. No change in the power or frequency of OE oscillations was observed after sectioning the olfactory nerve, indicating that the OE oscillations have a peripheral source. Finally, application of 1.0 and 10 microM tetrodotoxin to the epithelium blocked OE oscillations in a dose-dependent and reversible manner, suggesting that peripheral olfactory oscillations are related to receptor neuron spiking.
Ambystoma↗
Axon-glia communication evokes calcium signaling in olfactory ensheathing cells of the developing olfactory bulb.
Olfactory ensheathing cells (OECs) accompany receptor axons in the olfactory nerve and promote axonal growth into the central nervous system. The mechanisms underlying the communication between axons and OECs, however, have not been studied in detail yet. We investigated the effect of activity-dependent neuronal transmitter release on Ca(2+) signaling of OECs in acute mouse olfactory bulb slices using confocal Ca(2+) imaging. TTX-sensitive axonal activity upon electrical nerve stimulation triggers a rise in cytosolic Ca(2+) in OECs, which can be mimicked by application of DHPG, an agonist of metabotropic glutamate receptors (mGluRs). Both stimulation- and DHPG-induced Ca(2+) transients in OECs were abolished by depletion of intracellular Ca(2+) stores with cyclopiazonic acid (CPA). The mGluR(1)-specific antagonist CPCCOEt completely inhibited DHPG-evoked Ca(2+) transients, but reduced stimulation-induced Ca(2+) transients only partly, suggesting the involvement of another neurotransmitter. Application of ATP evoked CPA-sensitive Ca(2+) transients in OECs, which were inhibited by the P2Y(1)-specific antagonist MRS2179. Co-application of CPCCOEt and MRS2179 almost completely blocked the stimulation-induced Ca(2+) transients, indicating that they were mediated by mGluR(1) and P2Y(1) receptors. Our results show that OECs are able to respond to olfactory nerve activity with an increase in cytosolic Ca(2+) due to glutamate and ATP release.
Adenosine Triphosphate↗
Olfactory bulb lesions in Alzheimer's disease.
The olfactory bulb (OB), with its comparatively simple and well-delineated connectivity, presents an interesting system for examining cell-specific pathology in neurologic degenerative disorders such as Alzheimer's disease (AD). We have found that in AD the large, efferently projecting neurons (mitral cells) of the OB degenerate, typically without classical Alzheimer neurofibrillary changes. In some cases, with less severe neocortical pathology, the terminal arborizations of olfactory nerve appear hyperplastic and are associated with focal accumulations of A-4 (beta-amyloid) immunoreactivity that are not detectable by standard amyloid stains. These abnormalities may represent a pathologic manifestation of normally occurring plasticity in the olfactory system.
Aged↗
Dynamic instability at liquid/vapor interface far from equilibrium.
Attempt has been made to elucidate the mechanism of electric potential oscillations at oil-aqueous solution interface involving adsorption at oil-vapor interface on a semi-theoretical basis. The mechanism stipulates adsorption of ammonia, amines and pheromones at the liquid-vapor interface followed by transfer of ions through membrane-aqueous solution interface and subsequent interaction of ammonium (amine) ions and carbocations from pheromones with diffusing halide ions from the bulk. Relationship of the above mechanism with sensing mechanism of smell by olfactory nerves has also been pointed out.
Adsorption↗
Excitable properties of olfactory receptor neurons.
Action potential-generating properties of olfactory receptor neurons in the olfactory epithelium of the salamander, Ambystoma tigrinum, were studied in control animals, and 2 and 4 weeks after olfactory nerve transection. The threshold for impulse generation in response to injected current was extremely low (74 +/- 46 pA). In addition, the discharge frequencies of the receptor neurons were exquisitely sensitive to small increments of injected current. These high sensitivities may be characteristic of small neurons and stand in contrast to the much lower sensitivities reported for large neurons. The high sensitivity has important implications for the input-output functions of this cell. After nerve transection, both the threshold and the frequency sensitivity decreased. These changes appear to be associated with increased potassium conductance, suggested by prominent membrane rectification and reduced amplitudes of later membrane action potentials in the spike trains. The olfactory receptor neuron appears to be a favorable model for exploring these properties.
Action Potentials↗
Distinct subsets of sensory olfactory neurons in mouse: possible role in the formation of the mosaic olfactory projection.
The axons of the primary sensory olfactory neurons project from the olfactory neuroepithelium lining the nasal cavity, onto glomeruli covering the surface of the olfactory bulb. Neuroanatomical studies have shown previously that individual olfactory glomeruli are innervated by neurons that are dispersed widely within the nasal cavity. The aim of the present study was to test the hypothesis that phenotypically unique subsets of primary sensory olfactory neurons, scattered throughout the nasal cavity, project to a subset of glomeruli in specific olfactory bulb loci. Immunochemical and histochemical analyses in neonatal mice revealed that the plant lectin, Dolichos biflorus agglutinin, bound to a subset of mature primary sensory olfactory neurons which express the olfactory marker protein. This subset of neurons was principally located in the rostromedial and dorsal portions of the nasal cavity and projected specifically to a subset of glomeruli in the rostromedial and caudodorsal portions of the olfactory bulb. Analysis of Dolichos biflorus-reactive axons revealed that these axons coursed randomly, with no evidence of their selective fasciculation, within the olfactory nerve. It was only at the level of the rostral olfactory bulb that a significant reorganisation of their trajectory was observed. Within the outer fibre layer of the bulb, discrete bundles of lectin-reactive axons began to coalesce selectively into fascicles which preferentially oriented toward the medial side of the olfactory bulb. These data demonstrated that a phenotypically distinct subset of primary sensory olfactory neurons exhibits a topographical projection from the olfactory epithelium to the olfactory bulb, and suggests that these, and other subsets, may form the basis of the mosaic nature of this pathway. Moreover, it appears that the outer nerve fibre layer in the rostral olfactory bulb plays an important instructive role in the guidance and fasciculation of olfactory sensory axons.
Animals↗
Labelling of olfactory bulb glomeruli following horseradish peroxidase lavage of the nasal cavity.
The transport of horseradish peroxidase (HRP) from the nasal cavity to the olfactory bulb was examined in rat. HRP was present primarily in the olfactory nerve and glomerular layer. In some animals the glomeruli were densely filled with product while in others there was considerable interglomerular variation in density. Examination of the decalcified noses revealed a restricted distribution of HRP in those rats with partially labelled olfactory bulbs. The presence of small groups of densely labelled glomeruli was also noted using the 2-deoxyglucose method to examine odor-induced metabolic activity.
Animals↗
Characterization of somatostatin- and cholecystokinin-immunoreactive periglomerular cells in the rat olfactory bulb.
Periglomerular cells (PG) are interneurons of the olfactory bulb (OB) that modulate the first synaptic relay of the olfactory information from the olfactory nerve to the dendrites of the bulbar principal cells. Previous investigations have pointed to the heterogeneity of these interneurons and have demonstrated the presence of two different types of PG. In the rat OB, type 1 PG receive synaptic contacts from the olfactory axons and are gamma-aminobutyric acid (GABA)-ergic, whereas type 2 PG do not receive synaptic contacts from the olfactory axons and are GABA immunonegative. In this study, we analyze and characterize neurochemically a group of PG that has not been previously classified either as type 1 or type 2. These PG are immunoreactive for the neuropeptides somatostatin (SOM) or cholecystokinin (CCK). By using double immunocytochemistry, we demonstrate that neither the SOM- nor the CCK-immunoreactive PG contain GABA immunoreactivity, which is a neurochemical feature of type 1 PG. Moreover, they do not contain the calcium-binding proteins calbindin D-28k and calretinin, which are neurochemical markers of the type 2 PG. Electron microscopy demonstrates that the dendrites of the SOM- and CCK-containing PG are distributed in the synaptic and sensory subcompartments of the glomerular neuropil and receive synaptic contacts from the olfactory axons. Therefore, they should be included in the type 1 group rather than in the type 2. Altogether, these data indicate that the SOM- and the CCK-containing PG may constitute a group of GABA-immunonegative type 1 PG that has not been previously described. These results further extend the high degree of complexity of the glomerular circuitry.
Animals↗
Rapid classical conditioning of odor response in a physiological model for olfactory research, the tiger salamander.
In recent years there have been a number of important advances in the understanding of cellular mechanisms related to olfactory function. Hypotheses regarding the complex relationships among odorant structure, physiological activity and behavioral outcome generated by these findings, however, remain largely untested due to a paucity of psychophysical data on stimulus discrimination in the same experimental species. Comparisons between behavioral and physiological responses are essential for elucidating the critical aspects of stimulus coding in sensory systems. We have developed a method for generating psychophysical data in one of the primary model species used in olfactory research, the tiger salamander, Ambystoma tigrinum. These psychophysical experiments are carried out under the same conditions as physiological experiments in our laboratory. Using classical conditioning, individual salamanders are trained over a period of 2-3 h to show skin potential responses to odor and not air. Failure to train using backward pairing demonstrates that the response is not due to sensitization or pseudoconditioning. The conditioned response is mediated by the olfactory pathway, as it is blocked by olfactory nerve section. We show that salamanders detect three odorants that are commonly used stimuli in physiological experiments (butyl alcohol, butyl acetate and amyl acetate), but cannot detect a fourth common experimental odorant, camphor. This method should be a powerful tool for studying olfactory information processing by providing data on discriminability of stimuli used in salamander physiological studies.
Acetates↗