Olfactory Nervous System Research Articles

Selective targeting of zebrafish olfactory receptor neurons by the endogenous OMP promoter.

The olfactory nervous system of fish, in particular zebrafish, has become a valid model for that of higher vertebrates. However, no genetic markers for olfactory specific cell types, e.g. the olfactory receptor neurons, have been established in this species. Olfactory marker protein (OMP) is a reliable marker for olfactory receptor neurons in several other vertebrates. We have cloned zOMP, the zebrafish homologue of olfactory marker protein. During development, zOMP is expressed exclusively in the olfactory placode, presumably in olfactory receptor neurons, as shown by in situ hybridization. In the adult nasal epithelium zOMP is found restricted to the sensory region. zOMP appears to be a single gene, without close family members. The 5'-flanking region lacks most of the expected regulatory sequence motifs, both general and cell type-specific ones. Nevertheless, it drives reporter gene expression strongly and specifically in olfactory receptor neurons during the whole developmental period examined. Thus the zOMP promoter constitutes a powerful tool which should be useful to selectively introduce a wide variety of genetic modifications into olfactory receptor neurons.

The minimum number of neurons in the central olfactory pathway in relation to its function: a retrograde fiber tracing study.

The present study was aimed at determining the functionally essential size of the neuronal population in the central olfactory nervous system. Using conditioned rats who had learnt to avoid repellent (cycloheximide) solution by olfaction, varying degrees of injuries were made to the lateral olfactory tract, a major central olfactory pathway connecting the olfactory bulb to the olfactory cortex. After examining their olfactory ability to discriminate cycloheximide solution from water, intact bulbar projection neurons (mitral cells) with fiber connections to the olfactory cortex were quantified using a retrograde fiber tracing technique. The numbers of retrogradely labeled mitral cells from the rats with normal olfaction ranged between 20 and 92% of the control value, while those numbers from the anosmic rats ranged between 0 and 22%. We conclude that the functionally essential neuronal population is approximately one-fifth of the total in the central olfactory pathway, a presumed threshold value in terms of the ability to avoid cycloheximide solution by olfactory discrimination.

Cell dynamics of calretinin-immunoreactive neurons in the rostral migratory stream after ibotenate-induced lesions in the forebrain.

It is now apparent that adult neurogenesis is taking place during life in the olfactory bulb (OB) of the rodent brain. In the olfactory nervous system, the precursor cells of the subventricular zone are known to continually proliferate, migrate through the rostral migratory stream (RMS) and differentiate into the bulbar neurons. The RMS, consisting of heterogeneous cell populations of the neural and neuronal precursor cells, is the unique forebrain structure that provides a long-distance migratory route for the precursor cells. The present study was undertaken to examine whether neuronal regeneration, focusing on calretinin-immunoreactive (+) cells, may proceed in the RMS following lesions induced by an excitotoxin. Two days after ibotenate injections, massive degeneration of calretinin (+) cells occurred in the RMS and its adjacent forebrains. Thereafter, calretinin (+) cells gradually increased in the RMS and reached above their control value 2 weeks after ibotenate injections. Removal of the OB also produced a marked increase in calretinin (+) cells in the RMS. Autoradiographic experiments using (3)H-thymidine showed that calretinin (+) cells were continually generated in the RMS and underwent neuronal turnover within 8 weeks in a normal condition. The results indicate that, in terms of calretinin (+) cells, neuronal differentiation and replacement is continually taking place within the RMS, and that the RMS is capable of repopulating those cells which were injured by ibotenate.

Genetic Manipulation of the Odor-Evoked Distributed Neural Activity in the Drosophila Mushroom Body

Odor-induced neural activity was recorded by Ca 2+ imaging in the cell body region of the Drosophila mushroom body (MB), which is the second relay of the olfactory central nervous system. The signals recorded are mainly from the cell layers on the brain surface because of the limited penetration of Ca 2+-sensitive dyes. The densely packed cell bodies and their accessibility allow visualization of odor-induced population neural activity. It is revealed that odors evoke diffused neural activities in the MB. Although the signals cannot be attributed to individual neurons, patterns of the population neural activity can be analyzed. The activity pattern, but not the amplitude, of an odor-induced population response is specific for the chemical identity of an odor and its concentration. The distribution pattern of neural activity can be altered specifically by genetic manipulation of an odor binding protein and this alteration is closely associated with a behavioral defect of odor preference. These results suggest that the spatial pattern of the distributed neural activity may contribute to coding of odor information at the second relay of the olfactory system.

TrkA expression in olfactory epithelium and bulb during development.

The purpose of the present study was to examine immunohistochemically the expression of high-affinity nerve growth factor receptor (trkA) in the olfactory nervous system of developing mice and of colchicine-treated adult mice. Olfactory epithelia of embryos and neonates showed trkA immunoreactivity not only in basal cells but in receptor cells, with trkA-immunoreactive olfactory nerve fibers in the subepithelium and the bulb. In adults, trkA immunoreactivity was found only in basal cells of olfactory epithelia. Olfactory epithelia of colchicine-treated adult mice, however, exhibited appearance of trkA-immunoreactive receptor cells and increased trkA immunoreactivity in olfactory nerve fibers. These findings indicate that expression of trkA continually occurs in the olfactory nervous system during life and that trkA can be highly expressed during development.

Power spectra of ongoing activity of the snail brain can discriminate odorants

To test the hypothesis that different odorants are likely to cause distinctive changes in the ongoing electrical activity of populations of olfactory cells, we investigated field potentials (FP) in the Helix brain and their alterations by odorants as seen by semimicroelectrodes in an isolated preparation of the rostrum with its olfactory organ and whole central nervous system. Five pure chemicals and two natural odorants were applied as stimulants. Signals recorded both from the procerebrum (PC) and the visceral ganglion (VG) were analyzed. In the PC the five pure chemical odorants induce stimulus-specific characteristic responses, mainly in the low frequency range (<15 Hz). Regardless of odor intensity, the frequency of the peak power of sustained induced activity is constant for each chemical: ammonia at 0.2±<0.02 Hz; formic acid at 0.36±0.03 Hz; 2-pentanol at 0.48±0.04 Hz; 2-butanol at 0.67±0.03 Hz; ethanol at 1.31±0.09 Hz (means±95% confidence limits). These peak power frequencies, which we define as ‘odor-specific frequencies’, are confined to the low frequency range of<2.5 Hz. Those of natural odorants are: onion at 0.36±0.14 Hz and apple at 1.1±0.25 Hz. The activities evoked in the PC propagate to VG. The order of behavioural aversion determined by withdrawal reactions of the tentacles, 1% ammonia>formic acid>2-pentanol>2-butanol>ethanol, coincides with ‘the order of molecular affinity’ as well as with the sequence of peak power frequencies. There seems to be a strong correlation among behavioural valence, chemical nature of an odorant, and odor-specific frequency. The finding that, in the Helix olfactory center, odor input is processed as odorant specific low frequency FP activity may represent some general phenomena of olfactory information processing.

Computation of molecular information in mammalian olfactory systems

The olfactory system is unique in that the sensory input is in the form of molecular information carried in odour molecules and that a huge variety of compounds can function as odour molecules. The mammalian olfactory system has neuronal networks that can process and integrate the molecular information for discrimination of odour molecules and for perception of olfactory images of objects. Recent rapid advances have begun to provide new insights into the functional logic employed by the main olfactory system for odour discrimination, for odour classification and for olfactory perception of objects. This review discusses how the odour molecule information is encoded, transmitted, processed and decoded at distinct anatomical structures (sensory epithelium, olfactory bulb and olfactory cortex) of the olfactory nervous system. We also discuss the functional network in the accessory olfactory system with regard to the processing of pheromonal information.

TrkA Expression in Mouse Olfactory Tract following Axotomy of Olfactory Nerves

The olfactory bulb is one of the brain regions that synthesizes the nerve growth factor (NGF). Functional roles of the bulbar NGF remain to be determined. The aim of the present study was, using an antibody specific to the high-affinity NGF receptor (trkA), to examine immunohistochemically the distribution of the NGF receptor in the mouse olfactory tract, under normal conditions and during regenerative processes. In normal mouse olfactory epithelia, trkA immunoreactive cell bodies were only seen in basal cells. Cell bodies of olfactory receptor cells did not express trkA immunoreactivity, but their neuronal processes (olfactory nerve fibres and bundles in the olfactory mucosa and the olfactory bulb) displayed trkA immunoreactivity. After axotomy of olfactory nerves, regenerating olfactory cells (basal cells and olfactory receptor cells) expressed trkA immunoreactivity in intramucosal and intrabulbar neuronal processes of olfactory receptor cells. These results suggest involvement of the bulbar NGF in the process of synaptogenesis and/or regeneration of the olfactory nervous system.

Computation of molecular information in mammalian olfactory systems

The olfactory system is unique in that the sensory input is in the form of molecular information carried in odour molecules and that a huge variety of compounds can function as odour molecules. The mammalian olfactory system has neuronal networks that can process and integrate the molecular information for discrimination of odour molecules and for perception of olfactory images of objects. Recent rapid advances have begun to provide new insights into the functional logic employed by the main olfactory system for odour discrimination, for odour classification and for olfactory perception of objects. This review discusses how the odour molecule information is encoded, transmitted, processed and decoded at distinct anatomical structures (sensory epithelium, olfactory bulb and olfactory cortex) of the olfactory nervous system. We also discuss the functional network in the accessory olfactory system with regard to the processing of pheromonal information.

きゅう神経系でのガレクチン‐１の役割

The olfactory nervous system is responsible for the detection of odors. Primary sensory olfactory neurons are located in a neuroepithelial sheet lining the nasal cavity. The axons from these neurons converge on to discrete loci or glomeruli in the olfactory bulb. Each glomerulus consists of the termination of thousands of primary axons on the dendrites of second-order olfactory neurons. What are the molecular mechanisms which guide growing olfactory axons to select sites in the olfactory bulb? We have shown that subpopulations of these axons differentially express cell surface carbohydrates and that these different subpopulations target and terminate in particular regions of the olfactory bulb. Interestingly, the olfactory neurons and glial components in the olfactory pathway between the nose and brain express galectin-1. By using in vitro assays of neurite outgrowth we found that both galectin-1 and it's ligands were capable of specifically stimulating neurite elongation. Examination of the olfactory system in galectin-1 null mutants revealed that a subpopulation of axons failed to navigate to their target site in the olfactory bulb. This is the first phenotypic effect observed in galectin-1 null mutants and indicates that galectin-1 has a role in the growth and/or guidance of a subpopulation of axons in the olfactory system during development.

きゅう覚障害に対するセレポートの効果

The therapeutic effect of bifemerane hydrochloride (Celeport®) was studied in 42 patients with loss of the sense of smell caused by the common cold (group C) or head trauma (group T) who failed to respond to conventional treatment such as intranasal administration of betamethasone sodium phosphate. Celeport was administered in a daily dose 150mg tid or 100mg bid for 2 to 20 months. We assessed the effect of Celeport on the threshold of olfactory sensation and perception using the T & T olfactogram. The patients of group C showed significant improvement both in the threshold of olfactory sensation and perception after treatment. On the other hand, those of group T showed no significant recovery either in the threshold of olfactory sensation or perception. The rate of improvement in aged patients with loss of smell caused by the common cold was better than that in young patients. Therefore, we assumed that in aged patients the location of olfactory pathology caused by the common cold is not only the olfactory mucosa and nerve, but also the olfactory central nervous system.

Human G(olf) alpha: complementary deoxyribonucleic acid structure and expression in pancreatic islets and other tissues outside the olfactory neuroepithelium and central nervous system.

G(olf) alpha is a G-protein originally believed to mediate signal transduction exclusively within the olfactory neuroepithelium and subsequently found to be a major stimulatory G-protein in the basal ganglia. Here we present evidence that G(olf) alpha is expressed in several other tissues. The human isoform of G(olf) alpha was isolated from two human insulinoma cDNA libraries. Comparison of the human sequence with rat G(olf) alpha shows 91% nucleotide identity (within the coding region) and 99% identity at the amino acid level. Northern and reverse transcriptase-polymerase chain reaction analyses indicated that G(olf) alpha is expressed in all human insulinomas examined thus far as well as in normal pancreatic islets. G(olf) alpha mRNA was also detected in testis, retina, brain, and liver. Western blot analysis of various mouse tissues demonstrated that the level of G(olf) alpha protein in islets is lower than that in the olfactory neuroepithelium and other parts of the brain; its expression in retina, lung, and spleen was moderately higher than that in islets, and its expression in testis approached that in olfactory neuroepithelium. G(olf) alpha was also detected by immunohistochemistry in mouse islets, human insulinomas, the epithelial lining of mouse epididymis, photoreceptor cells of mouse retina, and mouse lung alveoli. These findings suggest a role for G(olf) alpha in a diverse population of cells located outside the olfactory neuroepithelium and central nervous system.

Human G(olf) alpha: complementary deoxyribonucleic acid structure and expression in pancreatic islets and other tissues outside the olfactory neuroepithelium and central nervous system

G(olf) alpha is a G-protein originally believed to mediate signal transduction exclusively within the olfactory neuroepithelium and subsequently found to be a major stimulatory G-protein in the basal ganglia. Here we present evidence that G(olf) alpha is expressed in several other tissues. The human isoform of G(olf) alpha was isolated from two human insulinoma cDNA libraries. Comparison of the human sequence with rat G(olf) alpha shows 91% nucleotide identity (within the coding region) and 99% identity at the amino acid level. Northern and reverse transcriptase-polymerase chain reaction analyses indicated that G(olf) alpha is expressed in all human insulinomas examined thus far as well as in normal pancreatic islets. G(olf) alpha mRNA was also detected in testis, retina, brain, and liver. Western blot analysis of various mouse tissues demonstrated that the level of G(olf) alpha protein in islets is lower than that in the olfactory neuroepithelium and other parts of the brain; its expression in retina, lung, and spleen was moderately higher than that in islets, and its expression in testis approached that in olfactory neuroepithelium. G(olf) alpha was also detected by immunohistochemistry in mouse islets, human insulinomas, the epithelial lining of mouse epididymis, photoreceptor cells of mouse retina, and mouse lung alveoli. These findings suggest a role for G(olf) alpha in a diverse population of cells located outside the olfactory neuroepithelium and central nervous system.

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.

Structural and functional studies of the peripheral olfactory nervous system of male and female bumble-bees (Bombus hypnorum and Bombus terrestris)

Volatile chemicals are known to be essential factors that trigger or release different kinds of bumble- bees (Bombus sp.) behaviour, in intraspecific and interspecific relationships. Chemical analyses of the in- volved semio-chemicals are now in progress, and in parallel we have studied the nervous bases of identified odour recognition, for both males and females (queens and workers) of B. hypnorum and B. terrestns. The insects' antennae are provided with the sensory equipment for the detection of volatile compounds; the distribu- tion of placodea-type olfactory sensilla was studied by scanning electron microscopy. Responses of antennal sensory cells to floral and pheromonal components were recorded (EAG). Queens present the most numerous sensillar population and the highest amplitudes in EAG responses. These results might be linked to the polymor- phism of the body size and therefore to the antennal size of the three kinds of insects, the queens being the biggest in this insect population. Odour sensitivity depends on the molecular weight and the chemical func- tion of the tested molecules and appears to be higher for some floral compounds such as vanillin and pheromonal derivatives such as farnesol.

The olfactory nervous system of the old world monkey.

This paper reviews work on olfactory function performed in the author's laboratory over the last 10 years. The following aspects of this work are covered. Neocortical olfactory areas were studied in old world monkeys. Olfactory responses were found in the lateroposterior and centroposterior portions of the orbitofrontal cortex (LPOF and CPOF). The routes of the olfactory nerve pathways to the LPOF and the CPOF were examined. An olfactory pathway to the lateral hypothalamic area (LHA) was also studied. Using unanesthetized monkeys, information processing of odors was studied in the OB, PPF-MA, LPOF, MDmc, CPOF, and LHA. In the LPOF and LHA, half or more of the cells responded differentially to one odor. We have thus been able to clearly demonstrate discrimination of odors at the cell level in these areas.

Discrimination of odors in olfactory bulb, pyriform-amygdaloid areas, and orbitofrontal cortex of the monkey.

In the orbitofrontal olfactory area (LPOF) which was delineated in a previous paper, the capacity for odor discrimination was studied and compared with that in the anterior pyriform cortex (AP), the medial portion of the amygdala (MA), and the olfactory bulb (OB). Unanesthetized monkeys were used and eight odors were applied. 1. In the OB, 12.5% of the cells responded to only one odor, and the cells which responded to five odors were most numerous (25%). The total of the cells which responded to two, three, and four odors was 52%, which was less than the total of the cells responding to three, four, and five odors (67.5%). A small number oc cells responded to all eight odors (2.5%). The responses were classified as an increase (+type), a decrease (-type), or no change (no-type) in the rate of spike discharge. 2. In the AP and MA, no difference in the response patterns was found. The cells which responded to only one odor were 12.3% of the total, and the cells which responded to three different kinds of odors were most numerous (34.3%). The total of the cells responding to two, three, and four odors was 80%, much more than that in the OB. In addition, no cell responded to all eight odors. Concerning the response types, an increase followed by a decrease, or vice versa, in the rate of spike discharges (mixed-type) was observed which did not appear in the OB. Thus, an advance was found in the processing of olfactory information when compared with the OB. 3. A most striking finding in the LPOF was that 50% of the cells responded to only one odor. The cells which responded to two, three, and four odors decreased in this order, and no cell responded to more than five odors. These cells never responded to light or sound. 4. Using three very similar odors and five very different odors, it was apparent that the ability to discriminate odors of the same category is far more advanced in the LPOF than in the lower olfactory areas; and, in contrast, the lower olfactory areas also play a significant role in the discrimination of odors which belong to different categories. 5. It was concluded that the capacity for odor discrimination definitely improves along the olfactory nervous system from the lower to the higher areas. It is highly probable that a fine and sepcific discrimination of odors is performed in the LPOF.

Physiological mechanisms of the peripheral olfactory nervous system

Physiological mechanisms of the peripheral olfactory nervous system

Delocalized pi-electrons and odours.

THERE are several natural and synthetic compounds with odours which have been used to identify the substances. It has been noted1 that for a substance to stimulate the sensory processes of the nerves it is necessary that some molecules leave the main part of the substance and pass into the nasal cavity. Amoore2 considers in his steric theory of odours that airborne molecules are smelled when they fit into certain complementary receptor sites in the olfactory nervous system. Dyson3 suggested that there is a correlation between the osmic frequencies and the Raman shifts of the smelling body, because the latter shows evidence of intramolecular vibrations. Dyson1 classifies smelling substances according to the presence of characteristic groups in the organic compounds.

Relation of pyramidal tract activity to force exerted during voluntary movement.

in a series P of studies of the relation of discharge 01 pyramlda1 tract neurons (PTNs) to voluntary movement. The first of the previous studies (5) showed that PTN activity both at rest and during movement is related to axonal conduction velocity. PTNs with the highest axonal conduction velocities tend to be silent during motor quiescence and to show phasic activity in association with movement. PTNs with lower axonal conduction velocities are for the most part active even in the absence of movement; with movement they show both upward and downward modulation of their resting discharge frequency. A second study (6) was carried out to obtain information as to the point in the interval between stimulus and response at which PTN discharge takes place in association with a conditioned hand movement. It was found that for many PTNs, responses to the conditioned stimulus (the onset of a light) preceded the first peripheral electromyographic correlates of the conditioned response (wrist extension). The fact that these PTN responses preceded the electromyographic response showed that they were not consequent upon feedback resulting from the movement. 1