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General morphology and axonal ultrastructure of the olfactory nerve of the pike, Esox lucius.

The olfactory nerve of the European pike (Esox lucius) contains 5.1 X 10(6) axons with an average diameter of 0.20+/-0,04 micron and a length of 5.5 cm in 1 meter long pike. Each axon contains an average of 4 microtubules as well as neurofilaments, smooth endoplasmic reticulum and about 500 mitochondria per centimeter. The number of neurofilaments ranges from zero in 15% of the cross sections to over 10 in 6%. Neurofilaments generally occur in clusters located opposite to microtubule regions. Smooth ER can not be identified in 14% of the cross sections suggesting that this structure may not be continuous. Microtubules often display annular regions (halos) of low electron density ranging in size from 800 to 1300 A. Halos from adjacent tubules usually merge into regional halos. The ratio of axoplasm to glial cytoplasm is 4.4:1, while the ratio of axonal plasma membrane to glial plasma membrane exceeds 7:1. A 4 cm nerve contains 1280 cm2 of axolemma. This nerve represents an extreme in high density axonal packing and is therefore exceptionally well suited for biochemical, biophysical and physiological investigations.

Animals↗

Expression of extracellular matrix molecules and cell surface molecules in the olfactory nerve pathway during early development.

The spatial and temporal expression patterns of several extracellular matrix molecules--laminin and fibronectin and cell surface molecules, neural cell adhesion molecule (NCAM), L1, tenascin, chondroitin sulfate proteoglycan, and peanut agglutinin (PNA) binding sites--were investigated during early olfactory nerve development. NCAM and L1 have similar patterns: They are expressed in the olfactory nerve and on the olfactory receptor neurons (ORNs) commencing with the earliest olfactory axon outgrowth (E12-E15). Their expression patterns suggest that both NCAM and L1 are associated with extension and fasciculation of olfactory axons. A comparison of L1 and olfactory marker protein suggests that L1 is expressed predominantly on immature ORNs. Laminin has an unique punctate staining pattern in the developing olfactory pathway as early as E12. These laminin puncta might play a role in olfactory neurite outgrowth and guidance. At E14, when pioneer olfactory axons enter the brain, the laminin-positive meninges on the surface of the olfactory bulb primordium break down but remain intact in the rest of the telencephalon. This suggests a functional interaction between the olfactory axons and the glial-pial barrier. Fibronectin staining is diffuse throughout the cranial mesenchyme but is absent from the olfactory nerve pathway. No specific patterns of tenascin or chondroitin sulfate, were observed during early olfactory development. PNA binding sites were associated with olfactory axon fasciculation. The expression of several extracellular matrix molecules and cell surface molecules is spatially and temporally regulated in the developing olfactory system. These molecules, thus, may play functional roles in olfactory axon outgrowth, fasciculation, and/or guidance.

Animals↗

Histological and histochemical studies of the secretory components of the salamander olfactory mucosa: effects of isoproterenol and olfactory nerve section.

Secretory components of the salamander olfactory mucosa, sustentacular cells (SC), and Bowman's glands (BG), were examined histologically and histochemically. In the aquatic larval salamander, SC in sensory grooves contained secretory granules; the submucosa contained a single layer of homogeneous, ductless glands. In the land-dwelling adult salamander, SC spanning a flat epithelial sheet contained vesicles. Subjacent to the epithelium in both dorsal and ventral mucosae lay BG whose ducts opened at the surface of the epithelium. In the ventral mucosa, two additional layers of olfactory glands (OG) lying below the BG were identified; ducts were not observed in association with the OG. The beta-adrenergic agonist isoproterenol caused depletion of secretory granules from BG and OG of larval, young, and adult salamanders but had no discernible effect on SC. Histochemical techniques (Alcian blue at pH 2.5 and pH 1.0, high-iron diamine, and the periodic acid-Schiff reaction) demonstrated that SC contained neutral, acidic, and small amounts of sulfated mucopolysaccharides (MPS), BG and OG contained only neutral MPS. In contrast, glands under adjacent respiratory epithelium contained both acidic and sulfated MPS. Unilateral olfactory nerve section ( ONX ) caused changes in the histochemical reactivity of acidic and sulfated MPS in SC on the ipsilateral and later on the contralateral side. Neutral MPS staining became enhanced first in the OG that lay under the BG, then in BG cells, and later in the deepest OG layer. Ipsilateral changes preceded contralateral ones. At 24 days post- ONX , some acinar cells in the deep OG contained acidic but not sulfated MPS.

Animals↗

Calcium signaling in mitral cell dendrites of olfactory bulbs of neonatal rats and mice during olfactory nerve Stimulation and beta-adrenoceptor activation.

Synapses formed by the olfactory nerve (ON) provide the source of excitatory synaptic input onto mitral cells (MC) in the olfactory bulb. These synapses, which relay odor-specific inputs, are confined to the distally tufted single primary dendrites of MCs, the first stage of central olfactory processing. beta-adrenergic modulation of electrical and chemical signaling at these synapses may be involved in early odor preference learning. To investigate this possibility, we combined electrophysiological recordings with calcium imaging in olfactory bulb slices prepared from neonatal rats and mice. Activation of ON-MC synapses induced postsynaptic potentials, which were associated with large postsynaptic calcium transients. Neither electrical nor calcium responses were affected by beta-adrenergic agonists or antagonist. Immunocytochemical analysis of MCs and their tufted dendrites revealed clear immunoreactivity with antibodies against alpha1A (Cav2.1, P/Q-type) and alpha1B (Cav2.2, N-type), but not against alpha1C (Cav1.2, L-type) or alpha1D (Cav1.3, L-type) calcium channel subunits. Moreover, nimodipine, a blocker of L-type calcium channels, had no effect on either electrical or calcium signaling at ON-MC synapses. In contrast to previous evidence, we concluded that in neonatal rats and mice (P5-P8), mitral cells do not express significant amounts of L-type calcium channels, the calcium channel type that is often targeted by beta-adrenergic modulation. The absence of beta-adrenergic modulation on either electrical or calcium signaling at ON-MC synapses of neonatal rats and mice excludes the involvement of this mechanism in early odor preference learning.

Afferent Pathways↗

Peripheral origin of olfactory nerve fibers by-passing the olfactory bulb in Xenopus laevis.

After DiI injections into the diencephalon of Xenopus, two types of retrogradely labelled cells were found in the nasal area: (i) receptor cells in the olfactory epithelium and (ii) a small cell group located between the main olfactory epithelium and the vomeronasal system. These results reveal an extensive extrabulbar olfactory projection of olfactory receptor cells. Fibers of these cells do not terminate in the olfactory bulb but innervate targets in the diencephalon directly. The other type of retrogradely labelled cells, apparently, are not part of any epithelium. They resemble similar cell groups which have previously been regarded as part of the nervus terminalis system in other vertebrates.

Animals↗

Microsurgical anatomic features of the olfactory nerve: relevance to olfaction preservation in the pterional approach.

OBJECTIVE: The pterional approach represents the standard approach for most lesions of the anterior and middle cranial fossa. It requires some degree of frontal lobe retraction, which may result in temporary or permanent damage of olfaction because of nerve avulsion or mechanical compression. The purpose of this study, based on microanatomic dissection of human cadaveric specimens, was to review the microsurgical anatomic features of the nerve and suggest operative nuances that may contribute to reducing the rate of postoperative olfactory dysfunction. METHODS: Twenty olfactory nerves and tracts were examined in 10 human cadaveric heads obtained from three fresh and seven formalin-fixed adult cadavers. A standard pterional craniotomy was performed. The olfactory nerve was dissected from its arachnoidal envelopes and then mobilized for an average length of 30 mm (range, 25-35 mm). RESULTS: The possible retraction of the frontal lobe was 10 to 15 mm. More retraction invariably resulted in nerve disruption. CONCLUSION: The standard sylvian and basal cistern opening may be insufficient to guarantee preservation of olfactory function. Early identification and arachnoidal dissection of the nerve may reduce the rate of olfaction compromise. The opening of the subarachnoidal space should be performed in a proximal-to-distal manner to allow early visualization of the olfactory bulb and its dissection. The arachnoidal dissection should be performed with sharp instruments, avoiding any traction on the posterior portion of the olfactory tract. Any direct retractor compression should also be avoided to spare the microvasculature lying on the dorsal surface of the nerve.

Cadaver↗

The relationship of particle size to olfactory nerve uptake of a non-soluble form of manganese into brain.

The essential element, manganese, can produce chronic neuromotor impairment related to basal ganglia (BG) damage when it is presented in excessive quantities. The uptake and elimination patterns of manganese following ingestion have been well studied and, under normal conditions, excretion appears to keep manganese levels under tight control. Less is known about inhalation exposure, but it has been proposed that the lung might serve as a long-term reservoir for manganese transport into blood. Recent data suggest that a third route of exposure, transport by the olfactory nerve directly to the brain, might have importance in toxicology since such a route would bypass liver uptake and biliary excretion of manganese. In this study, we sought to determine how particle size and the use of a poorly soluble form of manganese might influence net systemic absorption of manganese dust and the potential role of the olfactory nerve in transport of manganese dioxide. Rats were exposed in nose-only exposure chambers to manganese dioxide (MnO2) aerosols of 1.3 and 18 microm mass median aerodynamic diameter (MMAD). The concentration of aerosols was kept constant at 3 mg/m3 as Mn. Following 15 days of exposure (five times per week for 3 weeks), rats were euthanized and tissues harvested for manganese determination carried out by graphite furnace atomic absorption spectroscopy. Small-particle MnO2 exposure resulted in an elevation in olfactory bulb manganese concentration, presumably through uptake by the olfactory nerve, but the effect was highly variable. While small increases in cortical and neostriatal manganese levels were also observed in these rats, they did not reach statistical significance. By contrast, there was no evidence of olfactory nerve MnO2 uptake in rats receiving the large-particle exposure.

Administration, Inhalation↗

Olfactory nerve stimulation-evoked mGluR1 slow potentials, oscillations, and calcium signaling in mouse olfactory bulb mitral cells.

Fast synaptic transmission between olfactory receptor neurons and mitral cells (MCs) is mediated through AMPA and NMDA ionotropic glutamate receptors. MCs also express high levels of metabotropic glutamate receptor 1 (mGluR1) whose functional significance is less understood. Here we characterized a slow mGluR1-mediated potential that was evoked by high-frequency (100-Hz) olfactory nerve (ON) stimulation in the presence of NBQX and D-APV, blockers of ionotropic glutamate receptors, and that was associated with a local Ca2+ transient in the MC dendritic tuft. High-frequency ON stimulation in the presence of NBQX and D-APV also evoked a slow, nearly 2-Hz oscillation of MC membrane potential that was abolished by the mGluR1 antagonist LY367385 (50 microM). Both mGluR slow potential and slow oscillation persisted in the presence of gabazine (10 microM), a GABA(A) receptor antagonist, and intracellular QX-314 (10 mM), a Na+ channel blocker. In contrast to a slow mGluR1 potential in cerebellar Purkinje neurons, the MC mGluR1 potential was not depressed by SKF96365 (< or =250 microM) and thus is likely not mediated by TRPC1 cation channels, nor was it potentiated by an elevation of intracellular Ca2+ level. Imaging with the Na+ indicator SBFI revealed a Na+ transient in the MC dendrite accompanying the mGluR1 slow potential. We conclude that the MC mGluR1 potential triggered by glutamate released from the ON supports oscillations and synchronizations of MCs associated within one glomerulus.

Animals↗

[Neuroblastoma of the olfactory nerve].

The histopathology of neuroblastomas of the olfactory nerve, especially the difficult differential diagnosis is described by means of our own observations, and compared with other less differentiated malignant tumours of the inner nose. Ultrastructural results are presented, histogenesis and classification of olfactory neuroblastomas in neuroepithelioma, neurocytoma and neuroblastoma are discussed. The literature is reviewed, whereby clinical symptoms, therapy and prognosis of these tumours are described.

Adolescent↗

Olfactory nerve stimulation-induced calcium signaling in the mitral cell distal dendritic tuft.

Olfactory receptor neuron axons form the olfactory nerve (ON) and project to the glomerular layer of the olfactory bulb, where they form excitatory synapses with terminal arborizations of the mitral cell (MC) tufted primary dendrite. Clusters of MC dendritic tufts define olfactory glomeruli, where they involve in complex synaptic interactions. The computational function of these cellular interactions is not clear. We used patch-clamp electrophysiology combined with whole field or two-photon Ca2+ imaging to study ON stimulation-induced Ca2+ signaling at the level of individual terminal branches of the MC primary dendrite in mice. ON-evoked subthreshold excitatory postsnaptic potentials induced Ca2+ transients in the MC tuft dendrites that were spatially inhomogeneous, exhibiting discrete "hot spots." In contrast, Ca2+ transients induced by backpropagating action potentials occurred throughout the dendritic tuft, being larger in the thin terminal dendrites than in the base of the tuft. Single ON stimulation-induced Ca2+ transients were depressed by the NMDA receptor antagonist D-aminophosphonovaleric acid (D-APV), increased with increasing stimulation intensity, and typically showed a prolonged rising phase. The synaptically induced Ca2+ signals reflect, at least in part, dendrodendritic interactions that support intraglomerular coupling of MCs and generation of an output that is common to all MCs associated with one glomerulus.

2-Amino-5-phosphonovalerate↗

Long-term depression at olfactory nerve synapses.

The synapses formed by the olfactory nerve (ON) convey sensory information to olfactory glomeruli, the first stage of central odor processing. Morphological and behavioral studies suggest that glomerular odor processing is plastic in neonate rodents. However, long-term synaptic plasticity, a cellular correlate of functional and structural plasticity, has not yet been demonstrated in this system. Here, we report that ON-->mitral cell (MC) synapses of 5- to 8-d-old mice express long-term depression (LTD) after brief low-frequency ON stimulation. Pharmacological techniques and imaging of presynaptic calcium signals demonstrate that ON-MC LTD is expressed presynaptically and requires the activation of metabotropic glutamate receptors but does not require fast synaptic transmission. LTD at the ON--> MC synapse is potentially relevant for the establishment, maintenance, and experience-dependent refinement of odor maps in the olfactory bulb.

Animals↗

The optical spike. Structure of the olfactory nerve of pike and rapid birefringence changes during excitation.

1. Electron microscope studies on the olfactory nerve of the pike revealed a population of 4.2 million, densely packed unmyelinated nerve fibres; 95% are small fibres (average diameter 0.19 mum, narrow modal class), 5% are larger (average diameter 0.6 mum). Each fibre is bounded by an axonal membrane with a bilayer structure (80 A thickness). 2. The olfactory nerve is birefringent (negative with respect to fibre axis) and shows at 20 degrees C an average retardation R = 23 mn. The birefringence becomes more negative on lowering the temperature. 3. With the passage of an action potential a rapid, transient increase of retardation--the optical spike-- occurs; deltaR = 0.04 nm. The optical spike corresponds to the time course of structural changes in the axon membrane during excitation; it begins later, peaks earlier and decays more quickly than the voltage changes as recorded externally in the present study.

Action Potentials↗

Blood supply of the olfactory nerve. Meningeal relationships and surgical relevance.

The authors report the results of a series of dissections and anatomic sections of the fronto-basal region of the brain and of the anterior cranial fossa in human cadavers. The constant presence of an arachnoidal cistern above the olfactory nerve was verified. The arachnoid separates from the pial membrane and forms a bridge with the ventral part of the olfactory bulb and tract, from the lateral edge of the olfactory sulcus to the medial edge of the gyrus rectus. The cistern is wide in its anterior portion, between the gyrus rectus and the olfactory bulb, and is reduced to a virtual slit in its posterior portion where the tract is lodged in the olfactory sulcus. The olfactory nerve can be separated without damaging fronto-basal arachnoidial adhesions over several centimeters. Dissection of this region after intravascular injection of colored media shows the constant presence of an artery destined to the olfactory bulb and tract. It originates either from the lateral surface of the anterior cerebral a. (segment A2), or from the medial fronto-basal a., and consistently provides terminal branches in front of the olfactory trigone in the medial olfactory sulcus. At their ventral extremity, the olfactory structures are therefore vascularised independently for several centimeters, from the lower face of the frontal lobe. The independent vascularisation of the olfactory nerve, the tenuous and easily detachable adhesions, and the actual presence of a true arachnoidal cistern all contribute to enabling surgical techniques which conserve olfactory function during anterior approaches.

Arachnoid↗

Recovery of structure and function following transection of the primary olfactory nerves in pigeons.

Preliminary experimentation on ring doves to ascertain whether they might regulate any aspects of their reproductive behavior in terms of olfactory cues was vitiated by the discovery that their sectioned olfactory nerves had apparently regenerated. Concurrent work on frogs has shown that the olfactory receptors degenerate after axotomy and are replaced by new ones. This phenomenon was studied in pigeons. All transected nerves were found to be healed. Electrical recording from the regenerated nerves revealed apparently normal receptor function and, indirectly, autonomic reflex responsiveness. Previously untrained pigeons learned an olfactory discrimination after reconstitution of the peripheral olfactory system using a conditioned suppression procedure. The olfactory nerves of trained pigeons were sectioned and the behavioral response recovered within 16-82 days. The gross sizes of primary olfactory nerves and olfactory bulbs were frequently much less than those of controls, but on the ultrastructural level there was no recognizable morphological deficiency in the receptor cellular organelles or terminal synaptic contacts in bulbar glomeruli. Recent results by other workers indicate that pigeons utilize olfactory cues in homing performance.

Action Potentials↗

Microglia in the olfactory bulb of rats during postnatal development and olfactory nerve injury with zinc sulfate: a lectin labeling and ultrastrucutural study.

Using isolectin (GSA I-B4) as a marker, this study examined the possible alterations of lectin-labeled membranous glycoproteins in microglial cells in the olfactory bulb of normal development and under experimentally induced degeneration. In light microscopy, several morphological types of microglial cells representing different degrees of cell differentiation were distributed in the bulb laminae. A gradient of microglial differentiation extending from the intermediate to superficial and intermediate to deep occurs in the bulb layers. The differentiation gradient and lectin labeling pattern of microglial cells in the developing bulb resembled those in other areas of the brain tissues. Differentiating microglia showed a gradual diminution of lectin staining when the nascent round cells transformed into the mature ramified cells. Microglia in the external plexiform layer of the olfactory bulb were the first to mature and the cells expressed very weak lectin reactivity. In mature or adult rats, some microglial cells showing intense lectin labeling were observed in the olfactory nerve layer, granule cell layer and subependymal layer. Ultrastructurally, lectin labeling was localized at the trans saccules of the Golgi apparatus. Microglial cells in other bulb laminae, however, exhibited a negative reaction for the isolectin at the Golgi apparatus. Following intranasal irrigation of zinc sulfate, some microglial cells in the olfactory nerve layer and glomerular layer were activated to become phagocytic cells with increased lectin labeling at their ramified processes. GSA I-B4 staining was also localized at their trans saccules of the Golgi apparatus. The lectin labeling pattern of these phagocytic cells resembled that of differentiating microglia in postnatal bulbs, suggesting that bulb microglia in the lesioned sites were activated through cell dedifferentiation into macrophages.

Animals↗

Time course of reinnervation of the olfactory bulb after transection of the primary olfactory nerve in the pigeon.

Horseradish peroxidase (HRP) histochemistry was used to study the time course of reinnervation of the pigeon olfactory bulb after simple transection of the primary olfactory nerve. At selected intervals (9, 13, 29, 61 and 93 days) after transection of the right olfactory nerve, a concentrated solution of HRP was instilled in both nasal cavities. Intracarotid perfusion was performed 3 days after nasal instillation of HRP and 40-microns sections of olfactory bulb processed with the tetramethylbenzidine (TMB)-HRP histochemical protocol to visualize olfactory receptor axon terminals reinnervating the glomerular layer of the bulb. The total area of reinnervation of four representative regions in the bulb of the transected side were compared with that on the control bulb. The area of innervation by newly reconstituted olfactory axons was approximately 17% of control values at the 12-day posttransection time interval. A progressive increase in the area of reinnervation was observed over time. Reinnervation of the right bulb was approximately 70% complete at the 32-day posttransection time interval and indistinguishable from the left control bulb at the 64- and 96-day posttransection time intervals. A uniform pattern of reinnervation of different bulb regions was observed at all time intervals. These results indicate that the peripheral olfactory system of the pigeon is capable of complete reconstitution after nerve transection. Our findings should be useful in guiding functional comparisons of normal and newly reconstituted peripheral olfactory systems in the pigeon.

Animals↗

[A case of basal encephalomeningocele (a transethmoidal type) containing the olfactory nerve].

An experience of operative case of basal (transethmoidal type) encephalomeningocele is reported. A 3-year-old boy complained of continuous, spontaneous cerebrospinal fluid rhinorrhea and right intranasal mass lesion. The rhinorrhea began when one year old. He suffered from meningitis at the age of two. When he was three years old, the intranasal mass and CSF rhinorrhea were perceived. On admission he had normal general status and no abnormality in neurological examination. The usual axial computed tomography showed a small mass in the intranasal cavity. But the continuity between the mass and brain parenchyma was not detected in this study. Metrizamide CT cisternography demonstrated it. Coronal CT scan visualized it more directly. We performed operation using bifrontal craniotomy and subfrontal approach. Brain parenchyma did not protrude into the frontal cranial base and expanding right olfactory nerve penetrated into the small defect at the right cribriform plate. The olfactory nerve was extracted as much as possible. The defect was filled with a few piece of muscle and coating with the adhesive agent was performed. Histological findings of operative specimen were abnormal olfactory nerve, normal brain tissue and arachnoid membrane. Post-operative state was uneventful. CSF rhinorrhea disappeared. Post-operative direct sagittal computed tomography visualized the encephalomeningocele extremely. Biopsy of the intranasal mass revealed brain tissue covered by normal nasal epithelium. Basal encephalocele is rare in Japan. We found 10 cases in the literature. It is important that we do not forget basal encephalocele in the difference of intranasal tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗