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PubMed1998

Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway.

Purpose: To assess the potential of delivering nerve growth factor (NGF) to the brain along the olfactory neural pathway for the treatment of Alzheimer's disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to anesthetized rats. The rhNGF concentrations in the brain were determined by enzyme-linked immunosorbent assay (ELISA). Results: Following olfactory administration, rhNGF reached the brain within an hour, achieving a concentration of 3400 pM in the olfactory bulb, 660–2200 pM in other brain regions and, 240 pM and 180 pM in the hippocampus and the amygdala, respectively. In contrast, little or no rhNGF was found in the brain following intravenous administration. Conclusions: A significant amount of rhNGF can be delivered to the brain via the olfactory pathway. The detection of rhNGF by ELISA indicates that rhNGF is delivered to the brain relatively intact. The rapid appearance of rhNGF in the brain suggests that it may be transported by an extraneuronal route into the brain via intercellular clefts in the olfactory epithelium. Further work to clarify the transport mechanism is underway. The olfactory pathway is a promising, non-invasive route for drug delivery to the brain, which has potential for the treatment of neurodegenerative diseases including Alzheimer's disease.

Journal Article↗
PubMed1997

Computational parallels between the biological olfactory pathway and its analogue 'the electronic nose': Part II. Sensor-based machine olfaction.

Over the last fifteen years, we have witnessed a rapid expansion in the development of artificial odour sensing systems, or so called 'electronic nose' systems. Whilst the power of this approach to flavour has undoubtedly been demonstrated by its recent application to various complex odours, it will be argued that the original research programme, aimed at developing a comparative model of the biological olfactory pathway, has degenerated into an attempt to obtain an ad hoc workable system, based around readily available sensor and pattern recognition (PARC) technologies. At the time, the first 'model' nose system reflected the limited understanding of sensory information processing carried out within the biological olfactory pathway. We are now presented with an opportunity to evaluate and re-assess the architecture for an electronic nose, in view of the recent advances in understanding the key processing principals exploited by the olfactory bulb and cortex in the identification and characterisation of molecular stimuli. In Part II of this paper, we examine the parallels that exist between the biological olfactory system and the electronic nose. It is shown that the two systems share many similarities in their architectures and other properties, such as odour delivery, nonspecific sensor/receptor response, sensor/receptor preprocessing and content addressable memory (CAM) function. Of particular importance, both systems need to overcome similar operating problems, such as sensor/receptor drift, degeneration and poisoning, limited sensor/receptor sensitivity, discrimination of odour quality invariant of intensity and also the identification of particular odour components within a mixture of background odours. Finally, a number of opportunities for improving the biological plausibility of electronic nose systems are suggested that may yield an improvement in performance.

Animals↗
PubMed1991

Spread of the CVS strain of rabies virus and of the avirulent mutant AvO1 along the olfactory pathways of the mouse after intranasal inoculation.

After intranasal instillation in the mouse, rabies virus (CVS strain) selectively infected olfactory receptor cells. In the main olfactory bulb (MOB), infection was observed in periglomerular, tufted, and mitral cells and in interneurons located in the internal plexiform layer. Beyond the MOB, CVS spread into the brain along the olfactory pathways. This infection is specific to chains of functionally related neurons but at the death of the animal some nuclei remain uninfected. CVS also penetrated the trigeminal system. The avirulent mutant AvO1, carrying a mutation in position 333 of the glycoprotein, infected the olfactory epithelium and the trigeminal nerve as efficiently as CVS. During the second cycle of infection, the mutant was able to infect efficiently periglomerular cells in the MOB and neurons of the horizontal limb of the diagonal band, which indicates that maturation of infective particles is not affected in primarily infected neuronal cells. On the other hand, other neuronal cells permissive for CVS, such as mitral cells or the anterior olfactory nucleus, are completely free of infection with the mutant, indicating that restriction is related to the ability of AvO1 to penetrate several categories of neurons. From these observations, we concluded that CVS should be able to bind several different receptors to penetrate neurons, while the mutant would be unable to recognize some of them.

Administration, Intranasal↗
PubMed2005

Localization and role of metallothioneins in the olfactory pathway after exposure to mercury vapor.

We have investigated the localization and physiological roles of metallothioneins (MTs) in the olfactory pathway after exposure to mercury (Hg0) vapor. Male MT-null and wild-type mice were examined for the distribution of mercury, MT immunoreactivity and MT-III mRNA expression. There were no signs of histological changes in MT-null or wild-type mice. Light and electron microscopy of the samples stained with autometallography demonstrated chronological transfer of exposed mercury granules to the olfactory bulb by way of the olfactory tract. Basal expression of MT-I and -II immunoreactivity was observed in supporting cells, basal cells and acinar cells of the Bowman's gland of the olfactory mucosa in wild-type mice even without mercury exposure. In situ hybridization showed that signals for MT-III mRNA dominated in the olfactory cells of the olfactory mucosa, neurons in the olfactory bulb and those of brain in MT-null and wild-type mice. No difference in these findings was observed between samples taken at any interval after mercury exposure.

Animals↗
PubMedDate not supplied

Sensory information processing in the frog olfactory pathways. Experimental basis for modeling studies.

In the frog, unitary electrophysiological recordings have been extensively used to investigate odor processing along the olfactory pathways. By comparing spontaneous and odor-evoked activities of neuroreceptor, mitral and cortical cells, we have collected fundamental data relating to coding abilities of the three olfactory levels, the olfactory mucosa, the bulb and the cortex. Based on a synthesis of our experimental data related to GABAergic and dopaminergic involvement in the olfactory bulb, this paper aims to match this information with computational data and to discuss some questions on bulbar processing. This paper is also devoted to further analyze original results on coding properties of two functionally evidenced neuron subpopulations in the olfactory cortex. Thus, the assumption according to which some cortical neurons may work as temporal integrators while others as coincidence detectors is presented. Moreover, the pertinence that the neural code may be carried by a single spike with varying latency was demonstrated.

Animals↗
PubMed2000

Transfer of dopamine in the olfactory pathway following nasal administration in mice.

PURPOSE: The aim of the study was to investigate whether dopamine is transferred along the olfactory pathway to the brain following nasal administration to mice. METHODS: [3H]-Dopamine was administered nasally or intravenously to female mice. Brain tissue samples were excised and the radioactive content was measured. The precise localisation of dopamine radioactivity in the brain was studied using autoradiography. The presence of dopamine or its metabolites in the olfactory bulb and mucosa was ascertained using thin layer chromatography (TLC). RESULTS: After administration of [3H]-dopamine into the right nostril, the amount of dopamine in the right bulb increased with time until. after 4 h, it was 27 times higher than in the left bulb. Among the other brain tissue samples, significantly higher amount of radioactivity was detected in the lateral olfactory tract. Radioactivity in the right olfactory bulb was shown by autoradiography to be selectively located in the peripheral layers 1 to 4 h after administration. Selective uptake of radioactivity was not seen in other regions of the brain. TLC data indicated that approximately 75% and 10% of the radioactivity in the olfactory bulb and mucosa, respectively, coeluted with dopamine. CONCLUSIONS: The results indicate that unchanged dopamine is transferred into the olfactory bulb following nasal administration of [3H]-dopamine.

Administration, Intranasal↗
PubMed2000

Convergence of multimodal sensory input onto higher-level neurons of the crayfish olfactory pathway.

Intracellular electrophysiological studies of lateral protocerebral interneurons (LPIs) in the crayfish Procambarus clarkii have revealed convergence of multimodal sensory information onto these higher-level cells of the crustacean central olfactory pathway. Antennular stimulation by odors or electrical shocks generates excitatory-inhibitory sequences in some LPIs as does electrical or hydrodynamic stimulation of the antennae. Photic stimulation of the ipsilateral compound eye generates excitatory responses in LPIs, usually in the form of trains of impulse bursts that are timed to the peaks of the spontaneous oscillatory activity that characterizes these neurons. Focal electrical stimulation of the olfactory lobe, the termination point of antennular afferent input, or the accessory lobe, where higher-level visual and tactile inputs converge, also generates brief excitation and a delayed, prolonged inhibition in LPIs. Both phases of this activity are thought to be transmitted to the lateral protocerebrum via deutocerebral projection neurons, which have extensive dendritic arborizations in the olfactory lobe and the accessory lobe. The excitatory pathway is thought to synapse directly with target LPIs, whereas the inhibitory pathway is probably indirect and mediated through GABAergic interneurons within the lateral protocerebrum. There is evidence that both presynaptic and postsynaptic inhibition suppress activity in LPIs. Preliminary observations suggest that a small cluster of neurons adjacent to the hemi-ellipsoid body are inhibitory to LPI activity. Multimodal inhibitory and excitatory modulation of LPI activity may play a part in the contextual identification of odors in the crayfish olfactory system.

Action Potentials↗
PubMed2000

Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities.

This study investigated how changes in nutritional motivation modulate odour-related oscillatory activities at several levels of the olfactory pathway in non-trained rats. Local field potential recordings were obtained in freely moving animals in the olfactory bulb (OB), anterior and posterior parts of the piriform cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic signal analysis detected changes in power during odour presentation for several frequency bands The results showed that in most cases odour presentation was associated with changes in a wide 15-90 Hz frequency band of activity in each olfactory structure. However, nutritional state modulated initial responses to food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band. Changes in nutritional state also modulated responses to repeated FO stimuli. Habituation was expressed differentially across structures with a clear dissociation between the two parts of the piriform cortex. Finally, systemic injections of scopolamine (0.125 mg/kg) selectively blocked expression of the nutritional modulation in the OB found in the beta band. These results suggest that internal state can differentially modulate odour processing among different olfactory areas and point to a cholinergic-sensitive beta band oscillation during presentation of a behaviourally meaningful odorant.

Animals↗
PubMed1990

Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein.

The regeneration of the olfactory neuroepithelium following olfactory bulbectomy or peripheral deafferentation was studied with mRNA probes and antibodies for B-50/GAP43 and for olfactory marker protein (OMP). Two stages in the regeneration of the olfactory epithelium could be discerned with these reagents. The first stage occurs following either peripheral deafferentation of the olfactory epithelium with Triton X-100 (TX-100) or after bulbectomy and is characterized by the formation of a large population of immature olfactory receptor neurons. These newly formed neurons express B-50/GAP43, a phosphoprotein related to neuronal growth and plasticity. During the second stage of the regeneration process the newly formed olfactory neurons mature, as evidenced by a decrease in their expression of B-50/GAP43 and an increase in the expression of OMP. This stage is only manifested if the developing neurons have access to the target olfactory bulb. Formation of a full complement of OMP-expressing neurons occurs only after peripheral lesion with TX-100. In contrast, following bulbectomy the reconstituted olfactory epithelium lacks its normal target and is compromised in its ability to recover from nerve damage, as evidenced by the presence of a large number of B-50/GAP43-expressing neurons up to 3 months after the lesion and its failure to establish a full complement of OMP-expressing neurons. These results demonstrate that the olfactory epithelium is capable of replacing its sensory neurons independently of the presence of its target, the olfactory bulb. However, the differential patterns of expression of B-50/GAP43 and OMP at long times after peripheral lesion with TX-100 or bulbectomy illustrate the profound effect the olfactory bulb has on neuronal maturation in reconstituted olfactory neuroepithelium.

Animals↗
PubMed1976

Denervation in the primary olfactory pathway of mice. III. Effect on enzymes of carnosine metabolism.

Carnosine (beta-Ala-L-His) is localized within the receptor neurons of the primary olfactory system. Carnosine synthetase, the enzyme responsible for its synthesis, is found in the primary olfactory pathway of the mouse at activities higher than that found in other body tissues and brain regions. Carnosinase, the degradative enzyme, is present at high activities, only in the olfactory epithelial portion of this pathway. Peripheral deafferentation or central denervation cause a selective decrease in the activity of carnosine synthetase in the reciprocal portion of the primary olfactory system implying specific localization within the receptor neurons. These data are consistent with a role for the dipeptide carnosine in olfactory neural transmission.

Animals↗
PubMedDate not supplied

Polysynaptic potentiation at different levels of rat olfactory pathways following learning.

This study was aimed at investigating the consequences of learning on late polysynaptic components of evoked field potential signals recorded in parallel at different levels of the olfactory pathways. For this, evoked field potentials induced by electrical stimulation of the olfactory bulb were recorded simultaneously in the anterior piriform cortex, the posterior piriform cortex, the lateral entorhinal cortex, and the dentate gyrus. The different parameters of late components were measured in each site before and after completion of associative learning in anesthetized rats. In the learning task, rats were trained to associate electrical stimulation of one olfactory bulb electrode with the delivery of sucrose (positive reward) and stimulation of a second olfactory bulb electrode with the delivery of quinine (negative reward). In this way, stimulation of the same olfactory bulb electrodes used for inducing field potentials served as a discriminative cue in the learning paradigm. The data confirmed previous observation that learning was associated with a lowering in late-component-1 intensity of induction in the posterior piriform cortex. The use of simultaneous recording allowed us to further specify the consequences of learning on late-component distribution in the studied network. Indeed the data showed that whereas before learning, late component 1 was rather uniformly distributed among the recorded sites; following learning, its expression was facilitated preferentially in the posterior piriform cortex and lateral entorhinal cortex. Furthermore, learning was accompanied by the emergence of a new late component (late component 2), which occurred simultaneously in the four recording sites. The possible involvement of potentiation of polysynaptic components in recognition and/or consolidation processes will be discussed.

Animals↗
PubMed1992

Olfactory pathways and the sense of smell.

Rats were trained using operant conditioning to detect isoamyl acetate vapor generated by an olfactometer. They received lesions of olfactory pathways and were tested for retention of the odor detection task and trained on two-odor tasks. Deficits in odor detection and two-odor discrimination were related to the extent to which lesions disconnected the olfactory bulb from the forebrain. Transection of only the lateral olfactory tract, only the anterior limb of the anterior commissure, or lesions of the olfactory tubercle had little effect but combined lesions of these structures produced severe deficits in both odor detection and discrimination. Only rats with almost complete transection of the olfactory peduncle or cortex were anosmic; those with transections that spared a small segment of tissue between the olfactory bulb and olfactory cortex had detectable olfactory function. The results are discussed with regard to efferent connections of the olfactory bulb.

Animals↗
PubMed1997

Developmental anatomy of the primary olfactory pathway in the opossum Monodelphis domestica.

It has been shown in previous studies that the marsupial central nervous system is born at a relatively immature state. Although olfaction is thought to play a role in guiding the locomotion of the newborn, the cellular substrates on which this notion is based have not been systemically investigated. This review article summarises the anatomical development of the primary olfactory pathway in the postnatal Monodelphis. The olfactory epithelium and bulb appear morphologically immature at birth although some of the olfactory neurons are shown to express olfactory marker protein. The olfactory tissues subsequently undergo a rapid sequence of developmental events during the first two postnatal weeks. The evidence shows that the marsupial and eutherian olfactory system share a similar temporal sequence of developmental processes although the former proceeds at a lag time of about 10-14 days compared to that a mice (using the date of birth as a common reference point). Much physiological and behavioral studies remain to be done before we can be certain about the time at which functional maturity is attained in this system.

Aging↗
PubMed1993

Developmentally regulated expression of CGRP in the mouse olfactory pathway.

The pattern of expression of the neuropeptide CGRP and its encoding mRNA has been determined by immunohistochemistry and in situ hybridization in the mouse olfactory pathway during development. Specific CGRP transcripts are first detected at E13 followed by the appearance of the peptide at E15. Both peptide and transcript are present until birth; their expression then appears to be down-regulated since postnatally the peptide is only observed in some olfactory receptor neurons. A monoclonal antibody that specifically recognizes the neurofilament subunit NF-M has been used in order to identify olfactory and trigeminal axons. Our results demonstrate that CGRP is expressed in olfactory neurons and their axons during development, thus supporting further its role as a differentiation factor during olfactory bulb ontogenesis.

Aging↗
PubMed1984

Functional anatomy of the peripheral olfactory system of the African lungfish Protopterus annectens owen: development of the primary olfactory pathway during postembryonic growth.

Seven specimens of the African lungfish ranging in size from 4 to 350 gm were used for the study of changes in the olfactory nerve and bulb during postembryonic growth as expressed by the increasing number of lamellae of the olfactory organ. Serial semithin sections were used, and the data were studied mathematically. The number of axons of the olfactory nerve, the surface area of the bulb, and the number of mitral cells increase exponentially; the mitral cell density decreases exponentially; and the calculated average convergence (counted axons/counted mitral cells) of axons onto the cells of the bulbar relay increases exponentially. Convergence figures obtained are smaller than those cited by other authors; two factors might explain this: first the mode of calculation, and second the fact that every year this fish undergoes a 6-month starvation stage marked by degeneration of the primary olfactory structure. A preliminary view of the primary olfactory pathway using serial-section reconstructions is proposed: An orderly projection of the mucosa onto the bulb takes place after a 90 degrees rotation of the system of two perpendicular axes which apply to both the olfactory organ and the olfactory bulb. This study suggests an original attempt at relating the postembryonic change in convergence and projection to the primary processing of the olfactory message.

Animals↗
PubMed1996

Immunohistochemical localization of metallothionein in the olfactory pathway of dogs.

Dogs raised in the open air were used in this study. Metallothionein (MT) immunoreactivity was observed in the nucleus and/or cytoplasm of sustentacular cells of the olfactory epithelium in the nasal mucosa, whereas there was few MT-positive cells in the respiratory epithelium. MT immunoreactivity was also observed in astrocytes in all layers of the the olfactory bulb cortex; glial cells surrounding the glomeruli in the olfactory bulb showed prominent immunoreactivity for MT. Adult dogs exhibited stronger immunoreactivity for MT than young. Northern blot analysis demonstrated substantial levels of MT mRNA in the olfactory mucosa and olfactory bulb. Physiological roles of MT localized in the olfactory pathway of dogs were discussed.

Age Factors↗
PubMed1999

In rats, odor-induced Fos in the olfactory pathways depends on the phase of the circadian clock.

We used immunostaining for Fos to study the effect of circadian clock phase on odor-induced neuronal activation in the olfactory system in rats. Brief presentation of cedar odor to rats housed in constant darkness stimulated Fos expression in the main olfactory bulb, anterior olfactory nucleus, piriform cortex, and several other odor-responsive structures, both in the subjective day and subjective night phases of the cycle. Fos expression in response to odor, but not basal expression, was greatly enhanced in the subjective night in all structures examined. These findings are consistent with the idea that odor-induced neuronal activation in the olfactory pathways is modulated by the phase of the circadian clock.

Animals↗