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PubMed1992

Receptor cell regeneration and connectivity in olfaction and taste.

The capacity of adult mammalian gustatory and olfactory receptor cells to regenerate and make synaptic reconnections provides examples that may be useful in initiating replacement of other kinds of sensory receptor cells. The sensory code for taste quality may not be degraded by taste receptor cell turnover because axons probably recouple to the appropriate type of new receptor cell by axon-receptor cell affinity. Experiments on the development and regeneration of taste receptor cells suggest that they regenerate and turn over by recapitulating the late but not the early steps in taste bud development. To evaluate the replacement of vertebrate olfactory receptors, we began by characterizing the spatial pattern of primary olfactory projections in rainbow trout. Contiguous clusters of HRP-labeled olfactory receptor neurons (ORN) make highly divergent projections to the olfactory bulb. Retrograde transport of fluorescent latex beads revealed that a given restricted site in the glomerular layer received axons from ORNs widely scattered in the epithelium. Hence, ORN axons do not form point-to-point or regional topographic maps. Rather, the olfactory epithelial sheet makes a plane-to-point or holographic-like projection, since any given point in the glomerular layer receives information from the entire olfactory epithelial plane. Receptor cells that reacted with the lectin pokeweed agglutinin were highly dispersed in the olfactory epithelium with axons widely scattered in the olfactory nerve. Yet, as a consequence of the extensive reaggregation of axons at the nerve-bulb interface, the lectin-positive axons fasciculated and converged into a subregion of the glomerular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Evidence for species differences in 'peripheral' benzodiazepine receptors: an autoradiographic study.

The presence, density and distribution of 'peripheral' benzodiazepine (BZ)-binding sites was investigated by autoradiography in the brains of rats, mice, guinea pigs and cats and in some areas of the dog and monkey brains, using [3H]Ro 5-4864 as a ligand. Marked interspecies differences were found in the distribution and densities of these sites. Rats and mice presented a low density of binding uniformly distributed throughout the brain with high densities concentrated in the ependyma, choroid plexus and olfactory nerve layer of the olfactory bulb. In contrast, guinea pig and cat brains presented relatively high concentrations of peripheral BZ binding sites throughout the grey matter ependyma and choroid plexus, but low in the olfactory bulb. Monkey and dog brains presented low densities of peripheral BZ binding sites, including the choroid plexus.

Animals↗

PubMed1988

Detection of glia-derived nexin in the olfactory system of the rat.

Glia-derived nexin (GDN) is a 43 kd cell-secreted protease inhibitor with neurite promoting activity. We have raised specific polyclonal antisera to rat GDN. These antibodies stain a single band at 43 kd on immunoblots of concentrated C6 glioma-conditioned medium and have been used to demonstrate that GDN is present in the olfactory system of the rat. One band at 43 kd is recognized by the GDN antibodies on immunoblots of olfactory bulb homogenate. Immunohistochemistry shows that GDN occurs predominantly in the olfactory nerve layer of the olfactory bulb and in the olfactory submucosa. Comparative studies with antibodies against vimentin, GFAP, and fibronectin suggest that anti-GDN recognizes cells associated with the olfactory system, but not exclusively the olfactory neurons themselves. Data from the immunohistochemical studies were confirmed by RNA blots and GDN mRNA expression throughout development of the olfactory bulb. The high levels of GDN in the rat olfactory system may be related to the continuous degeneration and regeneration phenomena taking place in these structures.

Amyloid beta-Protein Precursor↗

PubMed1996

Olfaction in birds: differential embryonic expression of nine putative odorant receptor genes in the avian olfactory system.

We have isolated nine putative odorant receptor genes from the chick, named COR1 to COR9, that belong to the large multigene family of olfactory G protein-coupled receptors found in the fish, rat, mouse, dog, and human. By combining genomic DNA blot analysis, low stringency library screenings, and several PCR analyses, we were able to detect approximately 20 COR genes in the chick genome highly related to COR1-9. By in situ hybridization of newborn and adult, COR expression was detected only in the olfactory epithelium, and exhibited a random spatial distribution. During development, COR expression was observed as early as embryonic stage E5. Different levels of gene expression were observed for the COR1-9 genes: at E5, COR1-6 expression was high compared to the expression of COR7, COR8, and COR9. Surprisingly, at E5, a row of COR1-6 positive cells probably associated with the olfactory nerve extended outside the olfactory placode, reaching the anterior pole of the developing forebrain. These results suggest that, in addition to their role as putative odorant receptors, some COR may play a role in the development of the avian olfactory system.

Amino Acid Sequence↗

PubMed2005

Distribution of aminopeptidase P like immunoreactivity in the olfactory system and brain of frog, Microhyla ornate.

The enzyme aminopeptidase P (AP-P) is encountered in diverse vertebrate and invertebrate phyla and is known to act on proteins and peptides by releasing their N-terminal amino acid when the penultimate amino acid is proline. The present study is the first attempt at visualizing distribution of this polypeptide in the brain of a vertebrate species. The distribution of this enzyme was studied immunocytochemically in the forebrain of frog Microhyla ornata using antisera directed against cytosolic aminopeptidase P (DAP-P) of Drosophila melanogaster. Receptor cells in the olfactory epithelium exhibited strong AP-P like immunoreaction (ir). Immunoreactive fibers arising from the olfactory epithelium as well as vomeronasal organ joined the olfactory nerve, entered into the olfactory bulb, or accessory olfactory bulb and terminated in distinct glomerular formations. Some immunoreactive fibers traveled caudally and terminated in discrete areas in the telencephalon or diencephalon. Strong AP-P-ir was also seen in the cells of pars intermedia and pars distalis of the pituitary. The pattern of immunoreactivity suggests a role for AP-P in the processing of olfactory information and in hypophysial regulation.

Aminopeptidases↗

PubMed2000

Levels of amino acid neurotransmitters during mouse olfactory bulb neurogenesis and in histotypic olfactory bulb cultures.

The developmental changes in the levels of amino acid neurotransmitters were analyzed by high pressure liquid chromatography during mouse olfactory bulb neurogenesis, from embryonic day (E)13 until the young adult age, between postnatal days (P)30 and P40. During the embryonic period, high levels of glutamate, aspartate and GABA were observed, with the values of GABA about 2-fold higher than those of glutamate and aspartate. At P0, the production of these neurotransmitters experienced birth stress as shown by a significant 2-fold reduction in their levels. During the first two postnatal weeks, a progressive increase in the glutamate content was detected diminishing slightly in the adult stage. The aspartate concentrations showed a maximal value at P3 and then decreased gradually until the second postnatal week; in the young adult age, its concentration was comparable with that of glutamate. The postnatal GABA contents increased progressively from birth to maturity, showing maximal levels at P3, P11 and in the adult. Throughout the studied developmental period, the concentration of glycine remained relatively low. With regard to taurine, very low concentrations were detected during the prenatal period but after birth, the taurine content gradually increased with age, and in the adult animal, its concentration was comparable with those of GABA and glutamate. Our data demonstrate the predominance of GABA and glutamate during olfactory bulb synaptogenesis, however, in the adult animal, both glutamate and aspartate exert the same influence in the excitatory synaptic transmission; in the adult inhibitory synaptic transmission, taurine appears to play an important neuromodulatory or neurotransmitter role as that of GABA. To determine the intrinsic neurotransmitter production, primary histotypic olfactory bulb cultures were prepared from mice at P10. The comparative analysis of in vitro neurotransmitter contents with those in in situ adult animal showed higher levels of endogenously produced glutamate, glycine and GABA in the olfactory bulb than the extrinsic ones coming from olfactory nerve axons and higher olfactory brain centers. On the other hand, most of aspartate and taurine neurotransmitters apparently come from extrinsically located neurons.

Age Factors↗

PubMed2003

Relationships between olfactory discrimination and head injury severity.

The goal of this study was to examine the relationship between brain injury severity and scores on both an olfactory identification test and on many widely used neuropsychological tests in 367 patients with head injuries of varying levels of severity. It was hypothesized that valid olfactory test scores would correlate highly with injury severity because both the olfactory nerves and the primary olfactory cortices are especially vulnerable to damage in closed head injury. After removing data of doubtful validity from cases failing effort tests, olfactory test scores were related to Glasgow Coma Scale scores (GCS), post-traumatic amnesia and radiological abnormalities more strongly than any of the neuropsychological test scores. Based on the assumption that post-traumatic amnesia is caused by a different mechanism than loss of core consciousness, it was also predicted that there would be no cases with a GCS less than 13 and with no post-traumatic amnesia. As predicted, there were no cases in this group. The results support previous studies showing greater olfactory impairment with increased severity of head injury.

Adult↗

PubMed2002

Visualization of in vivo olfactory uptake and transfer using fluorescein dextran.

Nasal administration of a 3 kDa fluorescein dextran (FD3) solution to rats resulted in transcellular absorption across the olfactory epithelium and transfer to the olfactory bulb within 15 min. After entering the lamina propria, FD3 was transferred in the connective tissue surrounding the olfactory nerve bundles to the olfactory bulb of the brain. More FD3 was absorbed across the olfactory epithelium than across the respiratory epithelium and to the nasal associated lymphoid tissue. Further, the amount of FD3 crossing the olfactory epithelium was region-dependent, with higher amounts absorbed in the turbinates than in the nasal septum. Plastic embedding and sectioning followed by fluorescence microscopy, enabled simultaneous visualization of FD3 in the mucosa and olfactory bulb, as well as the opportunity to store the tissue blocks for a prolonged period of time.

Administration, Intranasal↗

PubMed1996

Lotus lectin labels subpopulation of olfactory receptor cells.

Experiments were performed to test the hypothesis that subsets of olfactory receptor cells could be recognized based on their lectin binding and that mapping of their projections onto the olfactory bulb would reveal details of anatomic organization of the olfactory nerve projection to the olfactory bulb. The results from one lectin, Lotus, were examined in detail. Olfactory receptor cells in the lateral part of the main epithelium were labeled, as well as scattered cells in the remainder of the epithelium. Glomeruli labeled by Lotus were concentrated primarily in the region of the olfactory bulb that receives its input from the lateral epithelium, although scattered glomeruli could be identified in other regions. Within the terminal field of these axons there was a mosaic pattern, with some glomeruli densely labeled, some lightly labeled and others unlabeled. These findings support the notion that there are biochemically distinct populations of olfactory receptor cells having localized distributions in the epithelium, with axons that coalesce to terminate in specific glomeruli, rather than diffusely over their projection field.

Animals↗

PubMed1994

GABAergic and glutamatergic synaptic input to identified granule cells in salamander olfactory bulb.

1. Whole-cell patch clamp recording techniques were applied to granule cells in an in vitro salamander olfactory bulb preparation to study their morphology, membrane properties and pharmacology of postsynaptic responses to electrical stimulation of either the olfactory nerve (ON) or medial olfactory tract (MOT). Optical recordings of the same preparations stained with the voltage-sensitive dye RH414 were also made. 2. Anatomical reconstructions of biocytin-filled granule cells showed that they extend widespread spine-bearing dendrites and an axon-like process that branched within the external plexiform layer. 3. ON or MOT stimulation evoked a long-lasting depolarization, usually generating only a single action potential, in granule cells studied under standard recording conditions. Bath application of bicuculline methiodide (BMI, a GABAA receptor antagonist, 20 or 25 microM) enhanced the spontaneous and electrically evoked excitatory drive to granule cells. 4. The electrically evoked synaptic responses consisted of both excitatory and inhibitory synaptic inputs. Using symmetrical Cl- conditions inside and outside the cell to enhance Cl- currents, spontaneous and electrically driven BMI-sensitive inhibitory postsynaptic currents (IPSCs) were revealed, indicating that granule cells receive GABAergic synaptic input. 5. Bath application of GABA (250 microM to 1 mM) shunted and hyperpolarized granule cells as observed directly from whole-cell recordings and indirectly from cell-attached patch single channel recordings. 6. Bath application of the glutamate receptor antagonists 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX, 10 microM) and/or DL-2-amino-5-phosphonopentanoic acid (DL-AP5, 100 microM) showed that granule cell dendrodendritic EPSPs are shaped by both non-NMDA and NMDA receptors. 7. The time course and pharmacological sensitivity of both single granule cell responses and ensemble responses recorded optically in the deeper layers of the bulb correlated well. 8. It is concluded that salamander granule cells integrate several types of synaptic input, may have both dendritic and axonal output, and play a major role in generating voltage-sensitive dye signals in the olfactory bulb.

Afferent Pathways↗

PubMed1999

[Local injection of dexamethasone acetate suspension into the nasal mucosa in cases of olfactory disturbance].

Local injections of suspended steroid solution into the nasal mucosa were performed for 102 patients with olfactory disturbances. Dexamethasone acetate suspension in a concentration of 4 mg/0.5 ml was injected into the mucosa of the nasal septum on each side every 2 weeks for a total of 8 times. Mecobalamin and ATP were also administrated in a daily dose of 750 micrograms and 300 mg, respectively. Of the 102 olfactory disturbance patients, 32 patients had chronic sinusitis, 24 patients had common cold, 14 patients had allergic rhinitis, 9 patients had head trauma and the remaining 23 patients the reason for the disturbance was unknown. Using a visual analogue scale, improvements were found in 63.7%. We assessed the effect of this therapy on the threshold of olfactory sensation and perception using a T & T olfactogram. The overall mean values of olfactory sensation and perception were significantly improved; from 4.75 +/- 1.44 (SD) to 3.01 +/- 2.13 (SD) and from 5.30 +/- 0.88 (SD) to 4.19 +/- 1.60 (SD), respectively. All but the cases of head trauma showed significant improvement. Overall, 44 (43.1%) of the 102 patients were defined as having had a positive olfactory response to this treatment (an improvement in the average perception olfactory score of > = 1.0). In cases of chronic sinusitis, 15 (46.9%) of the 32 patients were positive. 12 (50.0%) of the common cold 24 patients, 7 (50.0%) of the 14 allergic rhinitis patients, 2 (22.2%) of the 9 head trauma patients and 11 (47.8%) of the 23 unknown etiology patients were positive for this treatment. Patients with severe olfactory dysfunction and anosmia showed a lower response than the patients who were mildly to moderately affected. Patients showing no response in the Alinamin intravenous test showed also lower improvement rates than those showing a normal response. Interestingly, 8 (27.6%) of 29 patients with a normal appearance of the olfactory clefts and no response for the Alinamin test responded positively to this treatment. This meant that the olfactory disturbance might be due to the existence of edema surrounding the olfactory nerve, not of the olfactory cleft. The improvement rate of patients treated within one year from the onset of these olfactory disturbance was better than the rate of those over one year. The present new therapeutic modality is very useful as a treatment which showed only be performed by otolaryngologists.

Adenosine Triphosphate↗

PubMed1983

The terminal nerve: a new chemosensory system in vertebrates?

Ganglion cells of the terminal nerve in goldfish are located in the olfactory nerve and bulb and send peripheral processes into the olfactory epithelium and central processes to the supracommissural nuclei of the telencephalon as well as to the retina. Correlations between terminal nerve projections and neurobehavioral studies suggest that the terminal nerve mediates responses to sex pheromones.

Animals↗

PubMed1998

Skull-base trauma: neurosurgical perspective.

Trauma to the cranial base can complicate craniofacial injuries and lead to significant neurological morbidity, related to brain and/or cranial nerve injury. The optimal management involves a multidisciplinary effort. This article provides the neurosurgeon's perspective in management of such trauma using a 5-year retrospective analysis of patients sustaining skull-base trauma. The salient features of anterior and middle skull-base (temporal bone) trauma are summarized, and the importance of frontal basilar trauma as well as brain injury is evident. With these injuries, all cranial nerves (except 9 to 12) are at risk; the olfactory nerve and the facial nerve are the first and second, respectively, to sustain injuries. This retrospective analysis provides a better understanding of cranial base trauma and its management. It emphasizes the multifaceted nature of such trauma and the need to recognize anterior skull-base complications, including cerebrospinal fluid leak and brain injury.

Adult↗

PubMed1981

Localization of synaptic responses in the in vitro turtle olfactory bulb using the [14C]2-deoxyglucose method.

Studies were carried out on the in vitro turtle olfactory bulb preparation with a modification of the [14C]-2-deoxyglucose (2-DG) technique. Electrical stimulation of either the dorsal or ventral division of the olfactory nerve produced broad bands of activity, spreading across laminae, in the corresponding half of the olfactory bulb. Pretreatment of the isolated preparation in a low calcium bath eliminated focal 2-DG uptake induced by electrical stimulation of the nerve. In contrast, pretreatment with the GABAergic antagonist, bicuculline, produced a notable increase in 2-DG accumulation. These findings are discussed in the light of the topographical innervation of the olfactory bulb by the olfactory nerve as well as the known synaptic organization of the olfactory bulb and the putative neurotransmitters operative in local circuits.

Animals↗

PubMed1981

Olfactory receptor cell staining using horseradish peroxidase.

Iontophoretic injection of horseradish peroxidase into severed olfactory nerve fascicles has been used to stain salamander olfactory receptor cell somata, their associated nerves, and their axonal terminations in the glomerular layer of the olfactory bulb. This technique gives homogeneous, Golgi-like staining of individually identifiable receptor cells and has permitted preliminary mapping of the topographical relationship between the loci of receptors in the olfactory mucosa and sites of their termination in the glomerular layer in the olfactory bulb.

Ambystoma↗

PubMed1994

Age and differentiation-related differences in neuron-specific tubulin immunostaining of olfactory sensory neurons.

Olfactory sensory neurons (OSNs) are unusual mammalian neurons because they are produced continually throughout adult life and because their production is upregulated after injury. Because OSNs also have an unusual immunological profile and do not bind the commonly used antibody markers for neurons, we sought new antibody markers for studies of OSN regeneration. In this report, we characterize the staining patterns of antibodies to the Class III beta, neuron-specific, tubulin (NST) in rat olfactory tissue sections, to determine if these antibodies specifically label OSNs. In tissue sections from newborn rats, monoclonal antibodies to NST labeled cell bodies and processes of both immature (olfactory marker protein, OMP, -negative) and mature (OMP-positive) OSNs. In tissue sections from adult rats, immature OSNs showed both cell body and dendrite staining with anti-NST, while mature OSNs showed little or no cell body staining. Mature OSNs appeared to have both axonal and dendritic anti-NST staining. Axonal staining was suggested by the complete labeling of the olfactory nerve bundles and the nerve fiber layer of the olfactory bulb. The extent of labeling was judged by comparison with anti-OMP staining. Mature OSN dendritic staining was suggested because a much higher number of dendrites were anti-NST stained in the epithelium than cell bodies. These changes suggest both age and differentiation-related changes in subcellular distribution of NST in OSNs. NST antibodies are thus good markers for all OSNs in the newborn rat, but selective markers for immature OSNs and mature OSN processes in the adult rat. NST antibodies may also be useful probes for beta III tubulin function in neurons.

Age Factors↗

PubMed1973

Dischroism of the infrared spectrum of nerve.

Infrared spectra were obtained from the sciatic and optic nerves of the frog (Rana sp.) and the trigeminal and olfactory nerves of the garfish (Lepisosteus osseus). The myelinated nerves showed dichroism at several absorption peaks, particularly 1,220-1,230 cm(-1), but the nonmyelinated nerves showed little or no dichroism. The dichroic peaks indicate that in myelinated nerve, there is an ordered arrangement of protein and lipid molecules which was not found in nonmyelinated nerve.

Action Potentials↗

PubMed1989

Substance P-like immunoreactivity in the ganglion cells of the tench terminal nerve.

The distribution of substance P (SP) in the olfactory bulb of the tench Tinca tinca was studied by using an indirect immunoperoxidase technique. Many perikarya and processes of the ganglion cells of the nervus terminalis (NT) were strongly labeled. In addition, SP-like immunopositive fibers were observed in the proximity of these neurons and extending along the olfactory nerves and the olfactory tracts. The ganglion cells of the NT were not immunoreactive for methionine- and leucine-enkephalin, motilin, vasoactive intestinal polypeptide, neuropeptide Y, cholecystokinin-8, and tyrosine hydroxylase.

Animals↗