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PubMed1992

The human primary olfactory pathway: fine structural and cytochemical aspects during development and in adults.

Despite increasing knowledge about the biophysiology of the human olfactory system, understanding of the development of this pathway in humans lags considerably behind that of other vertebrates. Developmental studies have largely concentrated on the generation of cell types in the olfactory epithelium during the first trimester, while detailed ultrastructural observations usually describe the adult morphology. In this review, we have shown that contrary to what has been generally assumed, the surface of the human olfactory epithelium is heterogeneous and that its olfactory nerves differ ultrastructurally from those of other vertebrates studied. The development of the human primary olfactory pathway is discussed in terms of the appearance of olfactory bulb laminae, synaptogenesis and the expression of specific cell markers, such as the S-100 protein and olfactory marker protein (OMP). Positive immunohistochemical staining for N-cadherin in human fetuses suggests that growth of olfactory axons to their target may be mediated by cell adhesion molecules. The overall data presented here indicate that this pathway develops more precociously in humans than in rodents. Whether this translates also to earlier functional maturity remains to be elucidated.

Adult↗
PubMed1996

Central olfactory pathways in mosquitoes and other insects.

Studies of CNS processing of olfactory information have contributed significantly to understanding olfactory-guided behaviour in insects. Evidence in moths suggests that each glomerulus in the antennal lobes has a unique property: receptor-axon projections and dendritic arborizations of uniglomerular output neurons can relate to anatomically and functionally distinct glomeruli. Similar correlations are not typical of the concentrically organized locust antennal lobes. Insights about odour processing in the CNS of female mosquitoes should help us to understand how sensory information can lead to host-seeking behaviour. It will be interesting to learn how inputs from CO2 receptors on the maxillary palps and inputs from antennal olfactory receptors that respond to host odours are integrated centrally, so that pharmacological manipulation of olfactory neuron activity might provide a tool for the control of mosquitoes as important vector insects. The antennal lobe of male and female Aedes aegypti contains 20-25 glomeruli. Primary afferent projections from the antennae and maxillary palps target specific glomeruli of the ipsilateral antennal lobe. Maxillary palp projections are restricted to two posteromedial glomeruli, which do not receive antennal afferents. The latter arborize in the remaining glomeruli.

Animals↗
PubMed2005

Polysynaptic olfactory pathway to the ipsi- and contralateral entorhinal cortex mediated via the hippocampus.

Interactions between olfactory cortices and the hippocampus support sensory discrimination and spatial learning functions. The olfactory input accesses the hippocampal formation via a polysynaptic pathway mediated by the lateral and rostral entorhinal cortex (EC). We recently demonstrated that following repetitive stimulation of the lateral olfactory tract (LOT) at 2-8 Hz, a delayed response (onset at circa 60 ms) was evoked in the caudal portion of the EC, identified as medial EC, that does not receive a direct olfactory input. By performing simultaneous laminar profile analysis in the EC and in different hippocampal subfields, we conclusively demonstrate that the delayed EC response evoked by repetitive ipsilateral LOT stimulation is headed by the sequential activation of the dentate gyrus and the CA3/CA1 subfields in the septal and temporal hippocampus. Repetitive stimulation of the contralateral LOT also induced an EC response that peaked at 76.28+/-2.42 ms (n=15). Current source density analysis and time-delay analysis of simultaneous field potential laminar profiles performed from the EC and from DG, CA3 and CA1 hippocampal subfields suggested that the contralateral EC response is mainly carried by an intrahippocampal CA3-CA3 commissural pathway. Contralateral LOT stimulation also induced a later EC component (delay >100 ms) generated in the superficial layers, mediated either by local associative interactions or by extrahippocampal circuits. The opportunity to activate the ipsi- and contralateral olfactory pathways in the same experiment and to record field potentials profiles simultaneously in different structures of both hemispheres in the isolated guinea-pig brain confirms that this preparation is unique and is particularly suitable for investigating the system physiology of the limbic region. The present study demonstrates that patterned stimulation of the olfactory input that mimics sniffing patterns during odor discrimination induces a diffuse activation of both ipsi- and contralateral hippocampi and ECs. The findings contribute to the understanding the physiological mechanisms that underlie associative interactions between olfactory and non-olfactory cortical inputs converging into the mesial temporal region.

Animals↗
PubMed1989

Selective olfactory pathway lesions differentially affect runway behavior of the rat.

Selective bilateral lesions of the lateral olfactory tract (LOT) and/or the anterior limb of the anterior commissure (AAC) were performed on male rats and their influence on performance of a simple task studied. Rats had to enter and run down an alley for water reward. Whatever the lesion, all the rats succeeded in learning the task but some differences appeared in comparison with intact and sham-operated rats. AAC rats acquired faster the task, whereas LOT rats and AAC + LOT rats took longer to reach the learning criterion.

Animals↗
PubMed1991

Physiology and morphology of descending neurons in pheromone-processing olfactory pathways in the male moth Manduca sexta.

1. We have characterized the responses and structure of olfactory descending neurons (DNs) that reside in the protocerebrum (PC) of the brain of male sphinx moths Manduca sexta and project toward thoracic ganglia. 2. Excitatory responses of DNs to pheromone blends were of two general types: (a) brief excitation (BE) that recovered to background in less than 1 s after the stimulus, and (b) long-lasting excitation (LLE) that outlasted the stimulus by greater than or equal to 1 s and, in many cases, as long as 30 s. Individual pheromone components were ineffective in eliciting LLE. 3. Some neurons showing LLE also exhibited state-dependent responses to pheromonal stimuli. When such neurons were in a state of low background firing, stimulation with pheromone blend elicited LLE. When they were in a state of LLE, an identical stimulus reduced firing for 5-10 s after which firing gradually increased to the initial higher level. 4. Thirteen stained DNs were reconstructed from serial sections for detailed analysis of their morphology in the brain. DNs exhibiting LLE had neurites concentrated in the lateral accessory lobes (LALs) in the protocerebrum and adjacent neuropil. Most DNs exhibiting only BE to pheromonal stimuli and other DNs showing responses only to visual or mechanosensory stimuli did not have branches in the LALs.

Animals↗
PubMed2002

Visual arrestins in olfactory pathways of Drosophila and the malaria vector mosquito Anopheles gambiae.

Arrestins are important components for desensitization of G protein-coupled receptor cascades that mediate neurotransmission as well as olfactory and visual sensory reception. We have isolated AgArr1, an arrestin-encoding cDNA from the malaria vector mosquito, Anopheles gambiae, where olfaction is critical for vectorial capacity. Analysis of AgArr1 expression revealed an overlap between chemosensory and photoreceptor neurons. Furthermore, an examination of previously identified arrestins from Drosophila melanogaster exposed similar bimodal expression, and Drosophila arrestin mutants demonstrate impaired electrophysiological responses to olfactory stimuli. Thus, we show that arrestins in Drosophila are required for normal olfactory physiology in addition to their previously described role in visual signaling. These findings suggest that individual arrestins function in both olfactory and visual pathways in Dipteran insects; these genes may prove useful in the design of control strategies that target olfactory-dependent behaviors of insect disease vectors.

Amino Acid Sequence↗
PubMed1989

Estrogen differentially regulates neuropeptide gene expression in a sexually dimorphic olfactory pathway.

The posterodorsal part of the medial nucleus of the amygdala (MeAp) receives its major sensory input from the accessory olfactory bulb and projects massively to the medial preoptic nucleus and other sexually dimorphic hypothalamic nuclei thought to play key roles in mediating steroid-sensitive reproductive functions. A combined axonal transport/double-immunohistochemical method was used to show that at least one-quarter of the cholecystokinin-immunoreactive cells in the MeAp cocontain substance P and that a substantial proportion of these cells project to the medial preoptic nucleus. In situ hybridization histochemistry was then used to demonstrate that estrogen regulates the expression of preprocholecystokinin in these cells at the mRNA level in male and female rats. In contrast, levels of preprotachykinin mRNA within the MeAp do not appear to be sensitive to acute changes in circulating gonadal steroids in either sex. Although posttranscriptional regulation of mRNA stability may contribute to the observed effects, it appears likely that estrogen stimulates preprocholecystokinin expression within the MeAp by selectively inducing transcription of the corresponding gene, thereby altering the relative amounts of cholecystokinin and substance P coexpressed within individual neurons of the MeAp that project to the hypothalamus.

Amygdala↗
PubMed2000

Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes.

Manganese (Mn), administered intranasally in rats, is effectively taken up in the CNS via the olfactory system. In the present study, Mn (as MnCl(2)) dissolved in physiological saline, was instilled intranasally in rats at doses of 0 (control), 10, 250, or 1000 microg. At the start of the experiment each rat received an intranasal instillation. Some rats were killed after one week without further treatment (the 1-w group), whereas the remaining rats received further instillations after one and two weeks and were killed after an additional week (the 3-w group). The brains were removed and either used for ELISA-determination of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S-100b or histochemical staining of GFAP and S-100b, microglia (using an antibody against the iba1-protein) and the neuronal marker Fluoro-Jade. There were no indications that the Mn induced neuronal damage. On the other hand, the ELISA showed that both GFAP and S-100b decreased in the olfactory cortex, the hypothalamus, the thalamus, and the hippocampus of the 3-w group. The only effect observed in the 1-w group was a decrease of S-100b in the olfactory cortex at the highest dose. The immunohistochemistry showed no noticeable reduction in the number of astrocytes. We assume that the decreased levels of GFAP and S-100b are due to an adverse effect of Mn on the astrocytes, although this effect does not result in astrocytic demise. In the 3-w group, exposed to the highest dose of Mn, increased levels of GFAP and S-100b were observed in the olfactory bulbs, but these effects are probably secondary to a Mn-induced damage of the olfactory epithelium. Our results indicate that the astrocytes are the initial targets of Mn toxicity in the CNS.

Administration, Intranasal↗
PubMed1995

Elemental imbalances in the olfactory pathway in Alzheimer's disease.

Concentrations of 11 trace elements were determined in 56 control and 98 Alzheimer's disease (AD) olfactory bulb, olfactory tract, olfactory trigone, piriform cortex and amygdala specimens by instrumental neutron activation analysis. Iron and zinc were significantly elevated and bromine was significantly depleted in olfactory regions of AD patients, compared with normal age-matched control subjects. Elevated iron could possibly play a role in neuronal degeneration in AD by enhancing reactive free radical formation.

Aged↗
PubMed1999

Basic fibroblast growth factor in the primary olfactory pathway: mitogenic effect on ensheathing cells.

The mitogenic effect of basic fibroblast growth factor and nerve growth factor (2.5S) on olfactory ensheathing cell culture was examined by bromodeoxyuridine uptake. It was found that, at 10 ng/ml, basic fibroblast growth factor elicited about a three-fold increase in proliferation, while the stimulatory effect of nerve growth factor was considerably less. The increased proliferation resulting from basic fibroblast growth factor could be attributed to perlecan, which was shown to be expressed by ensheathing cell in culture. Perlecan is known to induce high-affinity binding of basic fibroblast growth factor to receptors on cell membranes. Immunohistochemical staining demonstrated that basic fibroblast growth factor was abundantly expressed in select regions of the lamina propria underlying the olfactory epithelium. In these regions, contiguous patches of olfactory epithelium also showed the presence of basic fibroblast growth factor. Although basic fibroblast growth factor was present on the periphery of nerve bundles in the olfactory nerve layer of the bulb, all other laminae did not demonstrate the presence of this factor. The immunohistochemistry and cell culture results show that regions of the lamina propria and small patches of the olfactory epithelium, by their presence of basic fibroblast growth factor, are potential sites of ensheathing cell proliferation in vivo.

Animals↗
PubMed2006

Dual olfactory pathway in the honeybee, Apis mellifera.

The antennal lobes (ALs) are the primary olfactory centers in the insect brain. In the AL of the honeybee, olfactory glomeruli receive input via four antennal sensory tracts (T1-4). Axons of projection neurons (PNs) leave the AL via several antenno-cerebral tracts (ACTs). To assign the input-output connectivity of all glomeruli, we investigated the spatial relationship of the antennal tracts and two prominent AL output tracts (medial and lateral ACT) mainly formed by uniglomerular (u) PNs using fluorescent tracing, confocal microscopy, and 3D analyses. Furthermore, we investigated the projections of all ACTs in higher olfactory centers, the mushroom-bodies (MB) and lateral horn (LH). The results revealed a clear segregation of glomeruli into two AL hemispheres specifically supplied by PNs of the medial and lateral ACT. PNs of the lateral ACT innervate glomeruli in the ventral-rostral AL and primarily receive input from T1 (plus a few glomeruli from T2 and T3). PNs of the medial ACT innervate glomeruli in the dorsal-caudal hemisphere, and mainly receive input from T3 (plus a few glomeruli from T2 and T4). The PNs of the m- and l-ACT terminate in different areas of the MB calyx and LH and remain largely segregated. Tracing of three mediolateral (ml) ACTs mainly formed by multiglomerular PNs revealed terminals in distinct compartments of the LH and in three olfactory foci within the lateral protocerebrum. The results indicate that olfactory input in the honeybee is processed via two separate, mainly uPN pathways to the MB calyx and LH and several pathways to the lateral protocerebrum.

Animals↗
PubMed1999

Dopamine receptor coupling to adenylyl cyclase in rat olfactory pathway: a combined pharmacological-radioautographic approach.

Dopamine binding sites of D1 and D2/D3 subtypes had been detected in the rat peripheral olfactory system and postulated to account for dopamine-dependent enhancement of olfactory memory and retro-inhibition of olfactory input within the olfactory bulb, respectively. We further assessed, in the present study, the mechanisms of these dopamine actions by using adenylyl cyclase activity assay and [35S]GTP radioautography in rat olfactory bulb and mucosa. The D1 agonist SKF 38393 increased adenylyl cyclase activity on membranes of the olfactory bulb, but not on those of the olfactory mucosa. Stimulation of adenylyl cyclase by SKF 38393 in the olfactory bulb was dose dependent, with a half-maximal effect (EC50) at 0.16 microM SKF 38393, reaching 40% over basal adenylyl cyclase activity, and was blocked by the D1 antagonist SCH 23390. The D2 agonists bromocriptine and quinpirole inhibited both basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. These adenylyl cyclase inhibitions were dose dependent, with EC50 values of 0.1-0.3 microM for bromocriptine and 1-3 microM for quinpirole, equal to 25% of basal enzyme activity at concentrations of 1-10 microM, and were blocked by the D2 antagonist eticlopride. The D2 antagonist was devoid of any effect on basal and forskolin-stimulated adenylyl cyclase activities in the olfactory bulb and mucosa. Odorant-induced stimulation of adenylyl cyclase was blocked by D2 agonist in olfactory mucosa membranes, which suggests dopaminergic regulation of odor detection in the olfactory mucosa. By using microdissected fractions of the olfactory mucosa, D2 agonist-induced inhibition of adenylyl cyclase was shown to occur only in lamina propria, thus co-localizing with D2 binding sites. [35S]GTP radioautography on tissue sections revealed D2 agonist-induced G-protein activation in olfactory nerve and glomerular layers of the olfactory bulb, and in the chorion of the olfactory mucosa. Taken together, these data demonstrate functional coupling of the dopamine receptors with adenylyl cyclase in both the olfactory bulb and mucosa, and document novel aspects of dopamine's physiological involvement in olfaction and of D2-mediated signal transduction.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

Cerebrospinal fluid absorption in the rabbit: olfactory pathways.

Twenty rabbits were intrathecally perfused with horseradish peroxidase (HRP) without increasing the cerebrospinal fluid (CSF) pressure. Histologic and ultrastructural studies of the olfactory nerve and nasal mucosa showed HRP along the space between peri- and epineurium down to the smaller nerve branches in the mucosa. Within the mucosa, HRP leaked out from the epineurium and flowed into: (a) lymphatic vessels; (b) mucous glands and ducts; (c) intercellular spaces of the nasal pseudostratified nasal epithelium; and (d) venules. These findings could account for "bulk" flow CSF absorption into the lymphatic system, the nasal cavity, and to a lesser degree, the venous system; also explain CSF rhinorrhea in man and experimental animals; as well as lymphatic drainage of CSF into cervical lymph nodes.

Absorption↗
PubMed1982

Functional changes in waking and sleeping rats after lesions in the olfactory pathways.

Food deprived control rats presented the following characteristics: (1) in a two-choice behavioral test, the animals explored significantly more the side of the cage odorized by a food odor (FO) than the non odorized one; (2) FO presentations in slow wave sleep (SWS) aroused them significantly more often than in a food satiated condition; (3) during wakefulness, the multiunit mitral cell responsiveness towards FO was selectively enhanced. The same 3 parameters have also been tested in animals where projections of one olfactory bulb were completely sectioned, or intact either in the medial or in the lateral part of one peduncle; the other olfactory peduncle was completely severed. The results showed that waking rats needed both medial and lateral projection pathways to perform normally in the food odor detection task, and to display the normal mitral cell excitability. However, in SWS, one medial pathway at least was needed to mediate normal rates of neocortical arousal in response to FO stimulations. The results are considered in terms of functional complementarity/redundance of the medial and lateral olfactory pathways.

Animals↗
PubMed1995

Quantitative analysis of the olfactory pathway for drug delivery to the brain.

Following intranasal administration to rats, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) concentrated in the olfactory nerve and glomerular layers of the olfactory bulb resulting in a mean olfactory bulb concentration of 140 nM. A negligible amount of label was detected in the olfactory bulb following intravenous administration of WGA-HRP or intranasal administration of unconjugated HRP. This is the first quantitative assessment of intraneuronal transport of a protein into the brain using the olfactory route.

Administration, Intranasal↗