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PubMed1981

Polarity of axoplasmic microtubules in the olfactory nerve of the frog.

Pieces of olfactory nerve of the bullfrog were extracted in a tubulin assembly buffer medium containing detergents. With incubation at 37 degrees C in such medium containing soluble tubulin, ribbons of protofilaments are formed on the surfaces of microtubules, with the ribbons curving in a clockwise or counterclockwise direction. The direction of hooking reflects the polarity of the microtubule. In nerve pieces oriented such that cross sections could be viewed toward the perikarya of the axons, over 90% of the ribbons on microtubules showed a clockwise orientation. When observers were looking toward the axonal terminals, most ribbons on microtubules showed a counterclockwise direction. In single axons in which ribbons appeared on all the contained microtubules, the ribbons showed a single directionality. The evidence suggests that microtubules in axons have a single polarity, probably reflecting their assembly from the perikarya outward through the axoplasm. If bidirectional transport is assumed in these axons, it is not reflected by the polarity of their microtubules, which may mean that the directionality of transport is provided by components other than microtubules.

Animals↗
PubMed1984

Transneuronal degeneration in different inbred strains of mice: a preliminary study of olfactory bulb events after olfactory nerve lesion.

Cytological analysis of the olfactory bulb was performed in two inbred strains of mice SEC/1 ReJ and C57/B16J after the lesion of the olfactory nerve. The data show an enhanced transneural degeneration in C57 mice as compared to the controls, while in the SEC mice this phenomenon did not exceed the level of spontaneous degeneration previously described by other authors. On the basis of our findings two different genetically adaptive systems are hypothesized and correlated with onto-genetical data.

Animals↗
PubMed1998

Changes in odor quality discrimination following recovery from olfactory nerve transection.

Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.

Animals↗
PubMed1981

Physiological activity of newly differentiated olfactory receptor neurons correlated with morphological recovery from olfactory nerve section in the salamander.

1. Extracellular unitary recordings were made from the olfactory epithelium of the salamander, Ambystoma tigrinum, at numerous time points following olfactory nerve section. Unitary response properties were correlated with histological examination of the same tissues. 2. At 10 days following nerve section, unitary activity was rarely recorded in all regions of the epithelium. Histological examination indicated that virtually the entire mature olfactory receptor cell population had undergone retrograde degeneration. Transneuronal degeneration was not observed in the olfactory bulb, although the olfactory nerve and glomerular layers were substantially reduced in size. 3. At subsequent times, unitary impulse activity gradually returned, consisting of both spontaneous activity and odor-evoked discharges. Anatomical recovery of the olfactory epithelium preceded that of the olfactory bulb. A positive correlation was found between neuronal differentiation in the olfactory epithelium and the recovery of receptor cell function. 4. Patterns of spontaneous activity, odor specificities, intensity-response functions, and adaptive properties studied in newly differentiated olfactory receptor neurons were indistinguishable from those observed in control units. This indicated that these properties were intrinsic to the receptor neurons. 5. Spontaneously active and responsive units were encountered prior to olfactory nerve connection with the bulb. It is concluded that receptor neurons pass through two phases of functional maturity: the first independent of bulbar contact and the second dependent on presumed synaptic contact with bulbar neurons.

Ambystoma↗
PubMed1991

Axonal transport of cadmium in the olfactory nerve of the pike.

109Cd2+ was applied in the olfactory chambers of pikes (Esox lucius) and the dynamics of the axoplasmic flow of the metal was determined in the olfactory nerves by gamma spectrometry and autoradiography. The results showed that the 109Cd2+ is transported at a constant rate along the olfactory nerves. The profile of the 109Cd2+ in the nerves showed a wave front of transported metal followed by a saddle region. When the nasal chambers were washed 2 hr after application of the 109Cd2+ well-defined transport peaks for the metal were seen in the olfactory axons. The maximal velocity for the transport of 109Cd2+, which corresponds to the movement of the wave front, was 2.38 +/- 0.10 mm/hr (mean +/- S.E.) at the experimental temperature (10 degrees C). The average velocity for the transport of the 109Cd2+, which corresponds to the peak apex movement of the wave, was 2.18 +/- 0.05 mm/hr (mean +/- S.E.) at 10 degrees C. The transported 109Cd2+ was strongly accumulated in the anterior parts of the olfactory bulbs, whereas in other brain areas the levels of the metal remained low. Autoradiography of a pike exposed to 109Cd2+ via the water showed a strong labelling in the receptor-cell-containing olfactory rosettes, whereas other structures in the olfactory chambers were only weakly labelled. The accumulation and axonal transport in the olfactory neurons may be noxious and constitute an important component in the toxicology of cadmium in fish, and this may apply also to some other heavy metals.

Animals↗
PubMed1987

A new method for the correction of hypertelorism with preservation of the olfactory nerve filaments.

A method for the preservation of the olfactory nerve filaments in cases of hypertelorism correction is described. The cribriform plate is completely resected and the nerve filaments gathered in the midline after medial rotation of the orbits. In contrast to Converse's (1970) procedure of paramedian osteotomies the method allows full correction of all degrees of hypertelorism, even in the most extreme cases, without olfactory nerve impairment.

Bone Diseases, Developmental↗
PubMed2006

Functional regeneration of the olfactory bulb requires reconnection to the olfactory nerve in Xenopus larvae.

Larvae of the South African clawed frog (Xenopus laevis) can regenerate the telencephalon, which consists of the olfactory bulb and the cerebrum, after it has been partially removed. Some authors have argued that the telencephalon, once removed, must be reconnected to the olfactory nerve in order to regenerate. However, considerable regeneration has been observed before reconnection. Therefore, we have conducted several experiments to learn whether or not reconnection is a prerequisite for regeneration. We found that the olfactory bulb did not regenerate without reconnection, while the cerebrum regenerated by itself. On the other hand, when the brain was reconnected by the olfactory nerve, both the cerebrum and the olfactory bulb regenerated. Morphological and histological investigation showed that the regenerated telencephalon was identical to the intact one in morphology, types and distributions of cells, and connections between neurons. Froglets with a regenerated telencephalon also recovered olfaction, the primary function of the frog telencephalon. These results suggest that the Xenopus larva requires reconnection of the regenerating brain to the olfactory nerve in order to regenerate the olfactory bulb, and thus the regenerated brain functions, in order to process olfactory information.

Animals↗
PubMed1992

The olfactory nerve contains two populations of glia, identified both in vivo and in vitro.

The peripheral olfactory nervous system exhibits, uniquely, neuronal cell body replacement and reestablishment of central connections in adult mammals. The role of the olfactory nerve glia in these phenomena is unknown, but information might be provided by in vitro systems. This paper reports on the characterization of olfactory nerve glia in dissociated cell cultures of newborn rat nasal mucosal tissues. The predominant type of glial cell resembled Schwann cells and immunostained for the S-100 protein, found in all glial cell types; glial fibrillary acidic protein (GFAP), found in astrocytes and nonmyelinating Schwann cells; and showed binding of 217C, a monoclonal Schwann-cell marker that binds to the low-affinity NGF receptor in glioma cells. They were negative for A2B5. The Schwann-cell-like olfactory glia changed morphology upon culturing in serum-free medium, with further shape changes after plating on laminin. Plating on laminin increased cell numbers. A second population, found only after GFAP-immunostaining, was astrocyte-like in morphology and represented approximately 10 percent of all glial cells. These were S-100-, A2B5-, and 217C-negative, a unique glial cell immunological profile. At low dilutions of anti-GFAP (1/10,000), or with weak fluorescent secondary antibodies, astrocyte-like glia were immunostained but Schwann-cell-like glia were not detectable. Astrocyte-like glia were not an artifact of the dissection, since they were detectable in tissue sections of newborn-rat olfactory nerves immunostained with a low dilution of anti-GFAP. The presence of two types of glial cells in culture suggests similarities between olfactory glia and enteric glia.

Animals↗
PubMed2005

Delayed olfactory nerve regeneration in ApoE-deficient mice.

Apolipoprotein E (apoE), a lipid transporting protein, is extensively expressed in the primary olfactory pathway, but its function is unknown. We previously reported increased apoE levels in the olfactory bulb (OB) following olfactory epithelium (OE) lesion in mice, and hypothesized that apoE may play a vital role in olfactory nerve (ON) regeneration. To directly test this hypothesis, we examined the rate of ON regeneration following OE lesion in apoE deficient/knockout (KO) and wild-type (WT) mice. OE was lesioned in 2- to 3-month-old mice by intranasal irrigation with Triton X-100 (TX). OB were collected at 0, 3, 7, 21, 42, and 56 days post-lesion. OB recovery was measured by both immunoblotting and immunohistochemical analysis of growth cone associated protein (GAP) 43 and olfactory marker protein (OMP). The results revealed that (1) OMP recovery in the OB was significantly slower in apoE KO compared to WT mice; (2) recovery of glomerular area was similarly slower; and (3) GAP43 increases and return to prelesion levels in the OB were slower in KO mice. Together, these results show that olfactory nerve regeneration is significantly slower in KO mice as compared to WT mice, suggesting apoE facilitates olfactory nerve regeneration.

Animals↗
PubMed1991

Development of the olfactory nerve in the African clawed frog, Xenopus laevis: I. Normal development.

Quantitative and morphological data were obtained on developing olfactory axons in the African clawed frog, Xenopus laevis, during late premetamorphosis (stages 48-54), prometamorphosis (stages 55-57), and halfway through metamorphic climax (stages 58-62). Larval axons throughout these stages of development did not change with respect to morphology or diameter and were similar in all respects to olfactory axons described in other vertebrate species. The number of axons in the olfactory nerve increased throughout development, more rapidly after stage 54. Based on comparisons of the number of axons in proximal and distal regions of the nerve, there also appeared to be more axons growing into the olfactory nerve at early metamorphic climax than during premetamorphosis. Through the onset of metamorphic climax, the number of olfactory axons was correlated with other measures of body growth. In the later stages of climax, however, the number of olfactory axons continued to rise, whereas body weight, length, and width, as well as olfactory nerve length, decreased. Not all animals developed at the same rate, but for all quantitative measurements in this study, stage was a better predictor of any given parameter than age of the animal. Rearing conditions affected the rate of development but did not have a significant effect on most of the features analyzed quantitatively. Although most of the new olfactory axons in these larval animals probably represent addition of fibers resulting from development, the ensheathing glial cells at all stages showed evidence of phagocytic activity, suggesting that there might be turnover of olfactory receptor cells during larval development. The results presented here provide a baseline for future reports on various factors that may influence normal development in this system.

Animals↗
PubMedDate not supplied

Reversible effects of olfactory nerve section on behavior and biochemistry in mice.

Coincident with the sectioning of the primary olfactory nerves in mice there is a dramatic loss of both olfactory-mediated behavior and the ability of the primary olfactory neurons to synthesize and transport the neuron specific marker, carnosine. These deficiencies are only temporary, and the ability of food deprived mice to locate buried food pellets returns within 21 days after olfactory nerve section. The ability of the primary olfactory neurons to synthesize and transport carnosine appears to increase between 8 days and 45 days after surgery. These data support the notion of behaviorally significant functional regeneration of olfactory neurons.

Alanine↗
PubMed1987

Activity-dependent changes in extracellular potassium and excitability in turtle olfactory nerve.

The excitability properties of turtle olfactory nerve (o.n.) were studied in vitro using potassium-sensitive microelectrodes (KSM), a modified sucrose gap chamber, and a standard nerve chamber to measure conduction velocity. A pronounced supernormal period (SNP), as indicated by increased conduction velocity of the o.n. fiber volley, lasting up to several seconds, was observed following a single stimulus. The compound action potential recorded in the sucrose gap chamber showed a prolonged depolarization with a similar time course to the SNP. When stimulation intensity was submaximal the response amplitude, and the extracellular potassium concentration [K+]o, continuously increased during repetitive stimulation. In contrast, when supramaximal stimuli were applied, the amplitude of the o.n. fiber volley was reduced during a high-frequency stimulus train for all responses after the initial one even though latency was maximally reduced, i.e., during supernormal conduction. Superfusion with various levels of K+ elicited changes in the excitability of the o.n. fibers. Small increases in [K+]o above the resting concentration of 2.6 mM led to an increase in resting excitability, whereas larger increases resulted in decreased excitability and conduction block. The SNP was eliminated when extracellular potassium was elevated between 3 and 4 mM above resting levels. Microstimulation of a small bundle of o.n. fibers led to an increase in [K+]o along the bundle but also around adjacent nonactivated fibers. The excitability of these neighboring nonactivated fibers was increased, further indicating the importance of activity-dependent changes in [K+]o in modulating axonal excitability. These results demonstrate the importance of activity-dependent increases in extracellular potassium in modulating nonmyelinated o.n. fiber excitability. They also indicate that increases in [K+]o and an associated membrane depolarization contribute to the increased excitability observed during fiber recruitment and the supernormal period.

Animals↗
PubMed1995

Tangential migration of luteinizing hormone-releasing hormone (LHRH) neurons in the medial telencephalon in association with transient axons extending from the olfactory nerve.

During embryonic development, luteinizing hormone-releasing hormone (LHRH) neurons migrate to the brain from the medial olfactory epithelium through the olfactory nerve. LHRH neurons enter the brain and migrate tangentially along the medial edge of the telencephalon in close association with a neural cell adhesion molecule (N-CAM) enriched fiber bundle. In the current work we wished to determine whether this N-CAM enriched fiber bundle is an extension of the olfactory nerve. Ablation experiments, immunocytochemistry and diI implants all suggest that LHRH neurons migrate in association with a very small subset of transient N-CAM enriched neuronal processes which extend out of the olfactory nerve proper to the septal-preoptic area.

Animals↗
PubMed1998

Molecular development of the olfactory nerve pathway.

There are, at least, two major questions concerning the molecular development of the olfactory nerve pathway. First, what are the molecular cues responsible for guiding axons from the nasal cavity to the olfactory bulb? Second, what is the molecular basis of axon targeting to specific glomeruli once axons reach the olfactory bulb? Studies in the primary olfactory pathway have focused on the role of extracellular matrix and ensheathing cells in establishing an initial substrate for growth of pioneer axons between the periphery and brain. The primary axons also express a multitude of cell adhesion molecules that regulate fasciculation of axons and hence may play a role in fascicle formation in the olfactory nerve. Although the olfactory neuroepithelium principally consists of a morphologically homogeneous class of primary olfactory neurons, there are numerous subpopulations of olfactory neurons expressing chemically distinct phenotypes. In particular, numerous subpopulations have been characterized by expression of unique carbohydrate residues and olfactory receptor proteins. Some of these molecules have recently been implicated in axon guidance and targeting to specific glomeruli.

Animals↗
PubMed2000

Dendritic cell-like immunoreactivity in the glomerulus of the olfactory bulb and olfactory nerves of mice.

Dendritic cell-like immunoreactivity was examined in the mouse brain. The glomerulus of the olfactory bulb and the olfactory nerves were stained by antibodies against the dendritic cells, NLDC-145 and MIDC-8, while these structures were not stained by antibodies against microglia or macrophages, F4/80, Mac1 or CD45. Immunoelectron microscopy showed that the immunoreaction for NLDC-145 was localized to the sheath and presynaptic terminals of the olfactory nerves. These findings suggest that the sheath and presynaptic terminals of the primary olfactory nerves have some degree of the antigenicity in common with dendritic cells.

Animals↗
PubMed1976

Olfactory nerve reconstitution in the homing pigeon after resection: ultrastructural and electrophysiological data.

Homing pigeons were subjected to uni- or bilateral resection of the olfactory nerves. A control of the operated region carried out five months later, showed that the olfactory nerves were continuous from the olfactory mucosa to the bulb. Cross sections of the regenerated nerve, observed under the electron microscope, showed morphological alterations with respect to the normal. Total measurement of the cross surface of both olfactory nerves showed that the regenerated nerve is always smaller than the intact nerve; this is also apparent in the total number of the fibres counted. Electrophysiological tests, performed on the regenerated nerve showed that the conduction along the resected nerve is restored.

Animals↗
PubMed2004

Lymphatic vessels gain access to cerebrospinal fluid through unique association with olfactory nerves.

BACKGROUND: Physiological studies suggest that a major portion of cerebrospinal fluid (CSF) drainage is associated with transport along cranial and spinal nerves with absorption taking place into lymphatic vessels external to the central nervous system. Especially important is CSF transport through the cribriform plate in association with the olfactory nerves. This study examined the anatomical connections that link the CSF and extracranial lymphatics at the base of the brain. METHODS AND RESULTS: The contrast agent, Yellow Microfil, was infused into the cranial sub-arachnoid compartment of 2- to 7-day-old lambs postmortem. In some animals, blue Microfil was perfused into the carotid arteries. Yellow Microfil was observed in extensive lymphatic networks in the submucosa associated with the olfactory and respiratory epithelium. Since little of the contrast agent was present within the interstitium of the olfactory submucosa, there appeared to be direct continuity between the subarachnoid space, the perineurial spaces of the olfactory nerve fibers that penetrated the cribriform plate, and the lumens of the lymphatic vessels within the olfactory submucosa. Lymphatics encircled the olfactory nerves at the level of the emerging nerve rootlets (in many cases providing the outer limit of the perineurial space) and then dispersed freely in the submucosa at greater distance from the crib-riform plate. These vessels converged into larger collecting ducts that emptied into various lymph nodes in the head and neck. CONCLUSIONS: Lymphatic vessels gain access to the brain extracellular fluid (CSF) in an unusual anatomical association with the olfactory nerves external to the cranial vault. This study highlights the important role played by lymphatic vessels in CSF absorption.

Animals↗
PubMed1987

A quantitative study of anterograde and retrograde axonal transport of exogenous proteins in olfactory nerve C-fibers.

The pike olfactory nerve which consists of a homogeneous population of C-fibers of 0.25 micron diameter or less was used to study quantitatively both anterograde and retrograde axoplasmic transport of wheat germ agglutinin and horseradish peroxidase. It was found that even in these extremely thin axons anterograde and retrograde transport takes place. Activity distribution profiles (transport profiles) for retrograde transport were established and found to be similar to the typical profiles of anterograde transport as they consisted of a small rapidly moving peak and a saddle region followed by the bulk of the material which moved more slowly. Horseradish peroxidase activity profiles were obtained both after injection into the synaptic region and after injection into the perikaryal region. From these transport profiles a maximal velocity of 25 mm/d (19 degrees C) for the leading peak and of about 7 mm/d for the slower component could be determined. There is no significant difference between the velocities for anterograde and retrograde transport. In the case of wheat germ agglutinin, only injection into the synaptic region resulted in typical transport profiles (retrograde transport) with a peak and saddle region. The maximum velocities of retrograde transport were about the same as for horseradish peroxidase [26 mm/d and 7 mm/d (19 degrees C)]. The electron microscopic analysis of horseradish peroxidase revealed that after injection into the olfactory bulb it was taken up into the neurons where it was found mainly in multivesicular bodies (0.5 micron diameter). In longitudinal sections of the nerve similar but slightly more elongated organelles (diameter 0.25 micron, length 0.4 micron) were found in those segments in which the slowly moving bulk of the peroxidase activity was located. The number of these organelles decreased with distance from the site of injection. The horseradish peroxidase transported within the leading peak could not be assigned to specific structures although several electron microscopic-histochemical methods were applied. It was concluded that anterograde and retrograde transport occur simultaneously in these axons, and that, therefore, even the large organelles, each of which almost fills the axon, must be able to pass each other. This would necessitate that the axons are able to transiently enlarge their diameter considerably.

Animals↗