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Odorant-specific adaptation pathways generate olfactory plasticity in C. elegans.

Following prolonged exposure to an odorant, C. elegans exhibits a diminished response to the odorant for several hours. This olfactory adaptation is odorant selective; animals can adapt independently to different odorants sensed by a single pair of olfactory neurons, the AWC neurons. The mechanism of olfactory adaptation is genetically complex, with different genes required for adaptation to different odorants. Animals mutant for the gene adp-1 fail to adapt to a subset of AWC-sensed odorants; adp-1 affects a calcium-dependent process required for adaptation. Mutations in another gene, osm-9, affect adaptation to a different but overlapping subset of AWC-sensed odorants. Mutations in adp-1 and osm-9 do not diminish the ability of unadapted animals to respond to odorants, indicating that odorant sensation and odorant adaptation are distinct processes.

Adaptation, Physiological↗

Estrogen-induced region specific decrease in the density of 5-bromo-2-deoxyuridine-labeled cells in the olfactory bulb of adult female rats.

Effects of chronic estrogen treatment on the survival rate of newly integrated interneurons were studied in the olfactory bulb of adult (250-300 g) female rats. Ovariectomized rats received 17-beta estradiol dissolved in sesame oil (i.p., 100 microg/100 g body weight [b.w.]) during six consecutive days, and on day 6 they were also injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU, i.p., 50 mg/kg b.w.) in every 2 hours during 8 hours. After 21 days of survival animals were killed and the density of BrdU-immunoreactive cells was analyzed in the granule cell and glomerular layer both in the main and accessory olfactory bulb. A significant decrease was found in the density of BrdU-labeled cells in both layers examined in the accessory olfactory bulb of ovariectomized and estradiol-treated rats when compared with those of ovariectomized and vehicle-treated animals. In the main olfactory bulb, in contrast, no difference was observed in the density of BrdU-immunoreactive cells in either of the two layers. Our results suggest that cells destined to the glomerular and granule cell layers react in the same way to chronic estrogen treatment, and the effect of estradiol is region specific, at least, within the olfactory bulb. 17-Beta estradiol reduces the density of newly generated cells in the accessory olfactory bulb, an area involved in the perception of pheromones, thus having a role in regulating sexual behavior, while the rate of integration and survival of newly born cells in the first relay station of the main olfactory pathway, i.e. the main olfactory bulb, remains unchanged.

Analysis of Variance↗

Olfactory capacities in aging and Alzheimer's disease. Psychophysical and anatomic considerations.

Age-related alterations in the ability to smell are well documented. For example, more than three-fourths of individuals over the age of 80 have major difficulty detecting and identifying odors. Furthermore, olfactory dysfunction is among the first signs of Alzheimer's disease (AD). Indeed, the olfactory pathways of patients with AD evidence disproportionate numbers of neuritic plaques and neurofibrillary tangles relative to other sensory pathways, suggesting that the olfactory system may be the site of first involvement of the AD process. In this article, the literature related to age- and AD-related alterations in olfactory perception has been briefly reviewed, and several current hypotheses regarding the physiologic basis for these changes discussed.

Aged↗

Crustacean-insect relationships: the use of brain characters to derive phylogeny amongst segmented invertebrates.

Conserved neural characters identified in the brains of a variety of segmented invertebrates and outgroups have been used to reconstruct phylogenetic relationships. The analysis suggests that insects and crustaceans are sister groups and that the 'myriapods' are an artificial construct comprising unrelated chilopods and diplopods. Certain elements of the optic lobes and mid-brain support the notion that insects are more closely related to crustaceans than they are to any other arthropods. However, deep optic neuropils and optic chiasmata are homoplastic in insects and crustaceans. The organization of olfactory pathways suggests that insect olfactory lobes originated late, probably first appearing in orthopteroid or blattoid pterygotes. The present results are discussed with respect to recent studies on early development of arthropod nervous systems and the fossil record.

Animals↗

Pathology of olfactory mucosa in patients with Alzheimer's disease.

Characteristic changes that appear in the biopsied olfactory mucosa of patients with Alzheimer's disease (AD) were examined with immunohistochemical staining. Specimens were obtained from patients with clinical diagnoses of AD. Patients with vascular dementia and age-matched patients without dementia were used for controls. In most AD cases, neurofibrillary tangle-like abnormal tau protein (Tau) immunoreactivity was seen in the dendrites and perikarya of the olfactory receptor cells and in the nerve bundles. A senile plaque-like extracellular mass was found in the olfactory epithelium, and it reacted strongly to an anti-Tau antiserum and weakly to an anti-amyloid-beta protein antiserum. Ubiquitin (Ubq) immunoreactivity was also observed in the dendrites. Tau immunoreactivity of the perikarya and extracellular mass, and Ubq immunoreactivity were especially characteristic of the olfactory mucosa of AD patients. From these results, it is clear that the same pathologic changes in the brain are also present in the olfactory mucosa of patients with AD. Not only disruption of the central olfactory pathway, but also an olfactory disturbance of AD patients is caused by peripheral changes. Furthermore, an olfactory mucosal biopsy could be a useful method for a definitive diagnosis of AD.

Aged↗

Evolution, discovery, and interpretations of arthropod mushroom bodies.

Mushroom bodies are prominent neuropils found in annelids and in all arthropod groups except crustaceans. First explicitly identified in 1850, the mushroom bodies differ in size and complexity between taxa, as well as between different castes of a single species of social insect. These differences led some early biologists to suggest that the mushroom bodies endow an arthropod with intelligence or the ability to execute voluntary actions, as opposed to innate behaviors. Recent physiological studies and mutant analyses have led to divergent interpretations. One interpretation is that the mushroom bodies conditionally relay to higher protocerebral centers information about sensory stimuli and the context in which they occur. Another interpretation is that they play a central role in learning and memory. Anatomical studies suggest that arthropod mushroom bodies are predominately associated with olfactory pathways except in phylogenetically basal insects. The prominent olfactory input to the mushroom body calyces in more recent insect orders is an acquired character. An overview of the history of research on the mushroom bodies, as well as comparative and evolutionary considerations, provides a conceptual framework for discussing the roles of these neuropils.

Animals↗

[Study of relations between the peripheral organ of olfaction and the olfactory bulb using anterograde and retrograde axon transport of horseradish peroxidase (HRP)].

Utilizing 26 Wistar albino rats, an anterograde and retrograde study has been performed on the connections between the first neuron of the olfactory pathway located in the olfactory epithelium and the second neuron in the glomeruli of the bulb. In the experiment we used horse radish peroxidase (HRP) in free form and combined with wheat lectin. In anterograde transport (epithelium-bulb), the HRP is deposited in preestablished sites in the olfactory epithelium of the nasal fossa. In retrograde transport (bulb-epithelium), HRP combined with wheat lectin is injected by means of a Hamilton microsyringe, glass micropipette and stereotaxic apparatus, in foreseen sites of the glomerular layer of the bulb.

Animals↗

A speculative essay on retinoic acid regulation of neural stem cells in the developing and aging olfactory system.

Circulating signals like the acidic derivative of vitamin A: retinoic acid (RA) may regulate resident stem cells in the adult nervous system, particularly in the olfactory pathway. RA is an essential factor for inducing neural stem or precursor cells that give rise to olfactory receptor neurons (ORNs) and olfactory bulb (OB) interneurons (OBINs) during embryonic development. Similar precursors in the adult brain constantly generate new ORNs and OBINs, and embryonic signaling pathways, like that via RA, may be retained or reactivated for this purpose. We have shown that RA regulates neural precursors in the embryonic and adult olfactory pathway. Moreover, RA administration after olfactory system damage stimulates an immune response and yields a more rapid recovery of olfactory-guided behavior. We suggest that olfactory integrity may be maintained by RA-mediated regulation of neurogenesis as well as local immune responses, and that aging compromises these mechanisms. The chemical senses, particularly olfaction, decline in aged individuals, and RA (via vitamin A) levels may also decline, perhaps due to changes in appetite and food intake. This synergy may result in a high prevalence of olfactory pathology in aged individuals.

Aged↗

Bilateral transection of the lateral olfactory tract but not removal of the vomeronasal organs inhibits short-photoperiod-induced testicular regression in golden hamsters.

It is now known that removal of the olfactory bulbs increases basal gonadotropin secretion and prevents short-photoperiod-induced testicular regression in Syrian hamsters. The experiments described in the present paper were an attempt to determine which neuronal systems associated with the olfactory bulbs are responsible for this influence on the reproductive neuroendocrine axis. In the first experiment, removal of the vomeronasal organ failed to influence gonadotropin secretion or testes weight in hamsters on long or short photoperiod, suggesting that the vomeronasal-accessory olfactory pathway is not individually responsible for the effect of the olfactory bulbs on gonadotropin secretion. In the second experiment, bilateral transection of the lateral olfactory tracts (LOT) did prevent short-photoperiod-induced testicular regression and the associated decrease in gonadotropin secretion. Since the nervus terminalis is confined to the surface of the medical olfactory bulb pathway, the results of LOT transection indicate that the nervus terminalis, which itself contains gonadotropin releasing hormone, does not mediate the influence of the olfactory bulbs on gonadotropin secretion. These results further suggest that the olfactory bulb influence on gonadotropin secretion is due to neural connections to the pyriform cortex, entorhinal cortex or amygdala.

Animals↗

Dendrites of mitral cell neurons contain microtubules of opposite polarity.

Axonal extensions of neurons show microtubules (MTs) with a uniform polarity indicating that they originate at or near the perikaryon. To obtain information on the polarity of dendritic MTs, a polarity assay was used to examine MTs in dendrites of interneurons (mitral cells) of the olfactory pathway of the bullfrog. The assay involved incubating pieces of olfactory lobe in a tubulin-containing detergent medium which stabilized pre-existing MTs and provided for assembly of exogenous tubulin onto their surfaces as ribbon structures, which appear as 'hooks' on the MTs when seen in cross-section. The orientation of the ribbons in a clockwise or anticlockwise direction reflects the polarity of the wall lattice of the MT with which they are associated. Mitral cell dendrites show MTs with ribbons oriented in both directions, indicating two populations of MTs with opposite polarity. The two populations are seen in both the proximal and distal regions of dendrites, and the perikaryon, as expected, shows a mixed population of MTs as regards polarity. It is hypothesized that this is true for most neurons, and that dendritic MTs arise from organizing centers in the dendritic process. If this hypothesis is correct, the polarity of dendritic MTs would depend on the orientation of these centers, which remain to be identified.

Animals↗

Transection of the lateral olfactory tract does not produce anosmia.

Rats trained in an olfactometer were tested for retention of an odor detection and odor discrimination task after lesions of the olfactory peduncle. Large lesions of the peduncle, including transection of the lateral olfactory tract and anterior commissure resulted in severe deficits in retention and relearning but did not produce anosmia. Discrete lesions of the lateral olfactory tract had little or no effect on retention. The results indicate that the lateral and intermediate olfactory pathways are not essential for smell and suggest that significant olfactory function may be mediated by medial olfactory bulb projections.

Animals↗

Olfactory ensheathing cells do not require L-ascorbic acid in vitro to assemble a basal lamina or to myelinate dorsal root ganglion neurites.

Ensheathing cells reside within both the PNS and CNS portions of the primary olfactory pathway and provide a glial covering and support for the unmyelinated olfactory axons. In vivo, these ensheathing cells express a mixture of astrocyte-specific and Schwann cell-specific phenotypic features. When grown in vitro in the presence of DRG neurons however, these ensheathing cells were observed to myelinate DRG neurites. The purpose of the present study was to determine whether ensheathing cells, like Schwann cells, require the addition of ascorbic acid to the medium in order to assemble a basal lamina and a myelin sheath. Our findings indicate that ensheathing cells can myelinate DRG neurites regardless of whether ascorbic acid is included in the growth medium and that these glial cells can assemble a basal lamina in the absence of added ascorbic acid. It appears from these results that Schwann cells and ensheathing cells have different growth media requirements for the assembly of a basal lamina.

Animals↗

Studies on the olfactory nervous system of the Old World monkey.

From the results of our electrophysiological and HRP studies in the old world monkey, multiple olfactory pathways have been clarified. The old world monkey has two neocortical olfactory areas, but no functional vomeronasal system. The response patterns to odors in various olfactory areas have also been studied. On the other hand, in the rabbit (Onoda and Iino, 1980) and dog (Onoda et al., 1981, 1982), which do have active vomeronasal systems, only one neocortical olfactory area was found. This important difference had already been indicated in three previous papers in which Takagi (1979, 1980, 1981) theorized that mammals can be divided into two groups according to their olfactory nervous mechanisms. One group includes old world monkeys, higher primates and man, and the other new world monkeys and lower mammals.

Animals↗

Pathological changes in olfactory neurons in patients with Alzheimer's disease.

Alzheimer's disease is a central nervous system disorder characterized by the presence of neurofibrillary tangles, neuritic plaques and dystrophic neurites in susceptible areas of the brain. Investigation of the mechanism and development of the disease has been hampered by the lack of an animal model and the inaccessibility of neural tissue during the illness. Deficits in odour detection and discrimination are among the signs of Alzheimer's and previous anatomical studies suggest that olfactory pathways may be involved early in the illness. Neurons in the olfactory epithelium, which are of central origin, are relatively accessible for biopsy and could be used as a source of living nerve cells for the study of Alzheimer's disease if they can be shown to have characteristics of this disease. As these neurons have the unusual property of arising from stem cells throughout the life of the organism, they are good candidates for the development of cell cultures or cell lines which may express the disorder from living patients. We report here that nasal epithelium tissue taken at autopsy shows unique pathological changes in morphology, distribution and immunoreactivity of neuronal structures in patients with Alzheimer's disease.

Adult↗

Role of laminin in axonal extension from olfactory receptor cells.

The role of laminin, an extracellular matrix molecule believed to be involved in axon extension, was explored in the outgrowth of olfactory receptor cells and therefore in the maintenance of organization in the olfactory pathway. First, immunocytochemistry was used to examine laminin expression in the olfactory nerve and bulb during development. Laminin immunoreactivity was high in the olfactory nerve and glomerular layers. Although it declined in intensity, laminin expression continued in the nerve and in single glomeruli of adults. Second, the influence of laminin on neurite outgrowth was examined in vitro using olfactory receptor cells harvested from E14 rat embryos. We developed an in vitro assay to quantify the substrate preference of outgrowing neurites. Cells were cultured for 48 h on coverslips coated with either poly-L-lysine alone, or poly-L-lysine overlaid with laminin. On laminin-coated regions of coverslips, the primary neurites of olfactory receptor cells were 52% longer than on the poly-L-lysine control substrates. In addition, the direction of the neurite outgrowth was influenced by laminin. Fifty-six percent of all receptor cells located in a defined area surrounding a laminin zone extended neurites onto laminin. In contrast, only 7% of all receptor cells located in the corresponding laminin zone extended a neurite onto poly-L-lysine. In summary, these data suggest that laminin provides a favorable substrate for the extension of the primary neurite from olfactory receptor cells and the direction of their extension. Therefore, laminin may be a factor underlying continuous olfactory receptor cell axon outgrowth and its pathfinding in the olfactory system.

Animals↗

Evolutionary changes in the olfactory projection neuron pathways of eumalacostracan crustaceans.

Output from the olfactory lobe (primary olfactory center) of eumalacostracan crustaceans is transmitted to the medulla terminalis (MT) and hemiellipsoid body (HB) in the lateral protocerebrum (higher order center) by a large population of projection neurons. In eureptantian crustaceans (lobsters, crayfish, and crabs), these projection neurons also form the output pathway from an additional neuropil, the accessory lobe (higher order center), which appears to have arisen de novo in these animals. In a previous study of lobsters and crayfish we showed that whereas projection neurons innervating the olfactory lobe project primarily to the MT, those innervating the accessory lobe project exclusively to the HB (Sullivan and Beltz [ 2001a] J. Comp. Neurol. 441:9-22). In the present study, we used focal dye injections to examine the olfactory projection neuron pathways of representatives of four eumalacostracan taxa (Stomatopoda, Dendrobranchiata, Caridea, and Stenopodidea) that diverged from the eureptantian line prior to the appearance of the accessory lobe. These experiments were undertaken both to examine the evolution of the olfactory pathway in the Eumalacostraca and to provide insights into the changes in this pathway that accompanied the appearance of the accessory lobe. The innervation patterns of the olfactory projection neurons of the species examined were found to differ markedly, varying from that observed in the most basal taxon examined (Stomatopoda), in which the neurons primarily project to the MT, to those observed in the two highest taxa examined (Caridea and Stenopodidea), in which they primarily target the HB. These results suggest that substantial changes in the relative importance of the MT and HB within the olfactory pathway have occurred during the evolution of the Eumalacostraca.

Animals↗

Fine structure of olfactory epithelia of gastropod molluscs.

Among gastropod molluscs the chemical senses are most important for location of distant objects. They are used in food finding, locating mates, avoiding predators, trail following, and homing. Chemoreceptors are commonly associated with the oral area, the tentacles, and the osphradium, which lies in the mantle cavity. Most chemosensory neurons are primary sensory neurons, although secondary sensory cells have been reported in the osphradium of some prosobranch gastropods. Most chemosensory organs contain sensory cells with ciliated sensory endings that are in contact with the external environment. Some sensory endings have only microvilli or have no surface elaborations. Cilia on sensory endings are commonly of the conventional type, but some species have modified cilia; some lack rootlets, some have an abnormal microtubular content, and some have paddle-shaped endings. The perikarya of sensory neurons may be within the sensory epithelium, below it, or in ganglia near the sensory surface. In some groups of gastropods there are peripheral ganglia in the olfactory pathway; in others chemosensory axons appear to pass directly to the CNS. Olfactory epithelia of terrestrial pulmonates have modified brush borders with long branching plasmatic processes and a spongy layer of cytoplasmic tubules which extend from the epithelial cells. Sensory endings of the olfactory receptors are entirely within this spongy layer. Aquatic pulmonates may have a similar spongy layer in their olfactory epithelia, but the cilia of sensory endings, as well as motile cilia of epithelial cells, extend well beyond the spongy layer.

Animals↗

The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats.

B50/GAP43 is a neuron-specific phosphoprotein whose expression is associated with neural development and synaptic plasticity. Its postnatal ontogeny was investigated in the primary olfactory pathway of the rat using immunohistochemical methods. The unique ability of the olfactory neuroepithelium to generate new neurons from a population of precursor cells present in the basal cell layer of this tissue makes it a valuable model in the study of neural development. In newborn rats B50/GAP43 is present throughout the entire population of olfactory receptor neurons. These cells are stained throughout, from the ciliated dendritic knob to their axon terminals in the bulb. This appears to be the first example of unambiguous B50/GAP43 expression in dendritic processes. With increasing age the distribution of this protein becomes progressively restricted to a subpopulation of olfactory neurons. Comparison of the expression of B50/GAP43 and the olfactory marker protein (OMP), a polypeptide only present in mature olfactory neurons, revealed that during postnatal development of the olfactory system these 2 proteins are expressed in a nearly reciprocal fashion. In adult animals (3.5 months-6 months of age), B50/GAP43-positive cells are exclusively present adjacent to the basal cell layer of the neuroepithelium. Basal cells appear to be unstained. The region of the epithelium containing the B50/GAP43-positive cells is virtually devoid of OMP-positive neurons. A significant fraction of these B50/GAP43-containing cells bear dendritic and neuritic processes. However, these cells do not express olfactory cilia. It is probable that the olfactory neurons expressing the growth-associated B50/GAP43 protein may correspond to a particular subset of olfactory neurons at an intermediate state of maturation.

Animals↗