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PubMed2000

Expression of semaphorins in developing and regenerating olfactory epithelium.

Semaphorins provide signals that guide growing axons to their appropriate destinations. The secreted semaphorin, Sema3A, mediates repulsive effects on axons from various neuronal populations in embryonic rats. The authors localized Sema3A mRNA expression in the primary olfactory pathway during development, in adult rats, and in adult rats that were subjected to a unilateral olfactory bulbectomy. Developing rats at ages from embryonic day 14 (E14) to E19 expressed Sema3A in the olfactory receptor neurons (ORNs) of the olfactory epithelium and in chondrogenic structures surrounding the nasal cavity. In vitro, ORN axons at E14 avoided substrate-bound Sema3A. Low levels of Sema3A expression persisted in the normal adult epithelium both in ORNs scattered throughout the epithelium and in small clusters. Three days after a unilateral olfactory bulbectomy, Sema3A transcript levels increased in regenerating neurons. High levels of Sema3A transcript were found at 1 week postbulbectomy, persisted for 2 weeks, and diminished by 3 weeks. Several other murine semaphorins (Sema4A, Sema4B, and Sema4C) were expressed differentially in the primary olfactory pathway both during development and regeneration. These findings suggest that Sema3A and perhaps other semaphorins play a role in directing ORNs out of the epithelium and to the olfactory bulb, their target structure, during both development and regeneration.

Age Factors↗
PubMed2005

Study on brain targeting of raltitrexed following intranasal administration in rats.

PURPOSE: To investigate the levels of raltitrexed (RTX) in blood and different brain tissues in rats and to find out whether there is any direct drug transport from nasal cavity to brain tissues following intranasal (i.n.) administration. METHODS: Raltitrexed was administered to male Sprague-Dawley rats either intranasally or intravenously. Drug concentrations in blood and brain tissues were determined at different times post dosing. RESULTS: The plasma levels achieved after i.n. administration were significantly lower than those following intravenous (i.v.) administration (P < 0.05) before 120 min; but were significantly higher (P < 0.05) after 120 min. Following i.n. administration, RTX concentrations in different brain tissues were constantly detected for quite a long time and differed significantly from each other, the rank order being C (OB) > C (OT) > C (CR) > C (CL). On the contrary, RTX appeared only at the initial two or three time points in different brain regions after i.v. injection, and the concentrations were similar. AUC values in four brain regions by the nasal route were 54- to 121-fold compared with the i.v. route, the drug targeting index (DTI) values of nasal route were 71-158 for different brain regions, and about 99% of RTX content within 360 min in the brain were transported via the olfactory pathway. CONCLUSIONS: These results showed that antineoplastic RTX could be directly transported into the brain via the olfactory pathway in rats.

Administration, Intranasal↗
PubMed2005

Olfaction: diverse species, conserved principles.

Olfaction is a vitally important sense for all animals. There are striking similarities between species in the organization of the olfactory pathway, from the nature of the odorant receptor proteins, to perireceptor processes, to the organization of the olfactory CNS, through odor-guided behavior and memory. These common features span a phylogenetically broad array of animals, implying that there is an optimal solution to the problem of detecting and discriminating odors.

Animals↗
PubMed2001

A central neural circuit for experience-independent olfactory and courtship behavior in Drosophila melanogaster.

We have studied the function of the major central olfactory pathway in fruit flies. Key elements of this pathway, the projection neurons (PNs), connect the antennal lobes with the lateral protocerebrum both directly and indirectly, the latter via the mushroom bodies (MBs). Transgenic expression of tetanus toxin in the majority of PNs and few MB neurons leads to defects in odor detection and male courtship. Considering behavioral data from flies lacking MBs, our results argue that the direct PN-to-lateral protocerebrum pathway is necessary and sufficient to process these experience-independent behaviors. Moreover, the involvement of an olfactory pathway in male courtship suggests a role of volatile attractive female pheromones in Drosophila.

Animals↗
PubMed1989

Neuroanatomical substrates involved in the control of food intake.

Five neural pathways were reviewed regarding their specific role in the control of food intake in birds. The five pathways included the trigeminal sensorimotor system, the visual system/basal ganglia pathway, the gustatory system, the olfactory pathway, and the autonomic nervous system/parasympathetic pathway. The trigeminal system is the pathway best understood among the five systems associated with feeding. It begins with sensory nerves innervating the upper and lower mandibles and buccal cavity and ends with nerves projecting to jaw muscles. The function of the pathway is to control the grasping and mandibulation of pellets or seeds. The visual system includes both the tectofugal and thalamofugal pathways. Both visual pathways interact with the avian paleostriatal complex. The latter is equivalent to the mammalian basal ganglia. The second pathway is important in food recognition as well as in orienting the body with respect to its position in three-dimensional space. The third neural circuit involves the sense of taste. Approximately 300 taste buds have been identified within the buccal cavity of the chicken, suggesting that the gustatory system is better developed than once thought. The fourth pathway involves the olfactory system; as in the visual system, more than one pathway has been identified. The dominant pathway appears to project to the piriform cortex, a structure that may play a role in monitoring essential amino acid contents of the brain. The fifth pathway involves an interaction of the hypothalamus and the dorsal motor nucleus of the vagus. This pathway is important in activating the parasympathetic nervous system and in preparing an organism to feed. All five pathways play different roles in controlling food intake in birds.

Animals↗
PubMed1990

Rapid activation of alternative second messenger pathways in olfactory cilia from rats by different odorants.

The molecular mechanisms mediating the chemo-electrical signal transduction in olfactory receptor cells are still elusive. In this study odor induced formation of second messengers in rat olfactory cilia was monitored in a subsecond time range using a rapid kinetic device. Application of micromolar concentration of citralva induced a rapid, transient elevation of the cyclic adenosine monophosphate level, whereas the concentration of inositol trisphosphate was not affected. In contrast, pyrazine caused a rise in the concentration of inositol trisphosphate, not affecting the level of cyclic adenosine monophosphate. Analysis of the kinetic parameter for the odorant induced reaction indicated that apparently two systems are operating simultaneously. The activating effects of odorants appear to be mediated via different G-proteins. Thus, at least two different second messenger pathways appear to be involved in olfactory signal transduction.

Animals↗
PubMed2005

Non-olfactory chemoreceptors in asymmetric setae activate antennular grooming behavior in the Caribbean spiny lobster Panulirus argus.

In the spiny lobster Panulirus argus the antennules carrying olfactory sensilla called aesthetascs and several types of other non-olfactory sensilla accompanying them are frequently groomed by the third maxillipeds in a stereotyped behavioral pattern. This behavior can be elicited by chemical stimulation with l-glutamate. Using selective sensillar ablations, we tested whether this behavior is driven by the numerous aesthetascs, which have been implicated as mediating this chemically elicited antennular grooming behavior in a previous investigation, or other, less numerous sensilla called asymmetric setae, which are tightly associated with aesthetascs. The selective sensilla ablations showed that the asymmetric setae are necessary and sufficient for driving chemically elicited antennular grooming. Bilateral elimination of the ca. 160 asymmetric setae almost completely abolished the behavior, whereas bilateral elimination of the ca. 2600 aesthetascs or of another type of sensilla associated with them (guard setae) did not cause a reduction in chemically elicited antennular grooming. Microscopical analysis of the morphological properties of the asymmetric setae revealed the presence of a terminal pore at the tip of the seta and a phalloidin-positive scolopale below its base. Since these structures have been identified in decapod crustaceans as modality-specific structures of bimodal chemo- and mechanosensory sensilla, we conclude that the asymmetric setae belong to this type of sensilla and thus have the appropriate features to function as chemoreceptors in the elicitation of antennular grooming. The identification of asymmetric setae and not aesthetascs as the drivers of chemically elicited antennular grooming suggests that it is not the olfactory pathway in the brain but a parallel pathway, constituted mainly by the lateral antennular neuropils, that is the neuronal substrate of this behavior. The lateral antennular neuropils receive non-olfactory sensory input from the antennule and contain the major arborizations of antennular motoneurons, allowing that direct sensory-motor coupling is involved in mediating the chemical elicitation of antennular grooming behavior.

Analysis of Variance↗
PubMed2001

Imaging and coding in the olfactory system.

Functional imaging methods permit analysis of neuronal systems in which activity is broadly distributed in time and space. In the olfactory system the dimensions that describe odorant stimuli in "odorant space" are still poorly defined. One way of trying to characterize the attributes of this space is to examine the ways in which its dimensions are encoded by the neurons and circuits making up the system and to compare these responses with physical-chemical attributes of the stimuli and with the output behavior of the animal. For documenting distributed events as they occur, imaging methods are among the few tools available. We are still in the early stages of this analysis; however, a number of recent studies have contributed new information to our understanding of the odorant coding problem. This paper describes imaging results in the context of other data that have contributed to our understanding of how odors are encoded by the peripheral olfactory pathway.

Animals↗
PubMed2004

Extrabulbar olfactory system and nervus terminalis FMRFamide immunoreactive components in Xenopus laevis ontogenesis.

The extrabulbar olfactory system (EBOS) is a collection of nerve fibers which originate from primary olfactory receptor-like neurons and penetrate into the brain bypassing the olfactory bulbs. Our description is based upon the application of two neuronal tracers (biocytin, carbocyanine DiI) in the olfactory sac, at the cut end of the olfactory nerve and in the telencephalon of the developing clawed frog. The extrabulbar olfactory system was observed already at stage 45, which is the first developmental stage compatible with our techniques; at this stage, the extrabulbar olfactory system fibers terminated diffusely in the preoptic area. A little later in development, i.e. at stage 50, the extrabulbar olfactory system was maximally developed, extending as far caudally as the rhombencephalon. In the metamorphosing specimens, the extrabulbar olfactory system appeared reduced in extension; caudally, the fiber terminals did not extend beyond the diencephalon. While a substantial overlapping of biocytin/FMRFamide immunoreactivity was observed along the olfactory pathways as well as in the telencephalon, FMRFamide immunoreactivity was never observed to be colocalized in the same cellular or fiber components visualized by tracer molecules. The question whether the extrabulbar olfactory system and the nervus terminalis (NT) are separate anatomical entities or represent an integrated system is discussed.

Animals↗
PubMed2002

Rare cause for short stature--Kallmann's syndrome--a case report.

Kallmann's syndrome is a neuroendocrine disorder, characterized by hypogonadotropic hypogonadism with hyposmia. We report a 27 year old male who presented with short stature and pain in the lumbar region. On detailed evaluation he had growth retardation, features of hypothalamic hypogonadism as evidenced by endocrimological tests and anosmia since birth. He had co-existent caries spine T10,T11 causing pain in the lumbar region-MRI brain showed normal olfactory pathway while the response to nasal stimulants was markedly attenuated. We present this case for its very care occurrence in the eastern part of the world and the typical feature being normal MRI brain with functional defect of the olfactory pathway.

Adolescent↗
PubMed2006

The vomeronasal system in mice: from the nose to the hypothalamus- and back!

The vomeronasal pathway in rodents runs parallel to the main olfactory pathway and mediates responses to different classes of chemosensory stimuli. Both olfactory systems can converge and synergize to control reproductive behaviors and hormonal changes triggered by chemosensory cues. Novel experimental approaches expressing genetic transneuronal tracers in hypothalamic neurons regulating reproduction have set the stage to analyze how chemosensory inputs are integrated in the brain to elicit reproductive behaviors and hormonal changes, and how neuroendocrine status might modulate susceptibility to chemosensory cues.

Animals↗
PubMed2000

Direct olfactory transport of inhaled manganese ((54)MnCl(2)) to the rat brain: toxicokinetic investigations in a unilateral nasal occlusion model.

Inhalation exposure of humans to high concentrations of manganese (Mn) is associated with elevated Mn levels in the basal ganglia and an extrapyramidal movement disorder. In the rat, direct olfactory transport of Mn from the nose to the brain has been demonstrated following intranasal instillation of (54)MnCl(2). However, the contribution this route makes to brain Mn delivery following inhalation is unknown and was the subject of our study. Male 8-week old CD rats underwent a single 90-min nose-only exposure to a (54)MnCl(2) aerosol (0.54 mg Mn/m(3); MMAD 2.51 microm). The left and right sides of the nose and brain, including the olfactory pathway and striatum, were sampled at 0, 1, 2, 4, and 8 days postexposure. Control rats were exposed to (54)MnCl(2) with both nostrils patent to evaluate the symmetry of Mn delivery. Another group of rats had the right nostril plugged to prevent nasal deposition of (54)MnCl(2) on the occluded side. Gamma spectrometry (n = 6 rats/group/time point) and autoradiography (n = 1 rat/group/time point) were used to compare the levels of (54)Mn found on the left and right sides of the nose and brain to determine the contribution of olfactory uptake to brain (54)Mn levels. Brain and nose samples from the side with the occluded nostril had negligible levels of (54)Mn activity, validating the nasal occlusion procedure. High levels of (54)Mn were observed in the olfactory bulb and tract/tubercle on the side or sides with an open nostril within 1-2 days following inhalation exposure. These results demonstrated, for the first time, that the olfactory route contributes the majority (up to >90%) of the (54)Mn found in the olfactory pathway, but not in the striatum, of the rat brain up to 8 days following a single inhalation exposure. These findings suggest that the olfactory route may make a significant contribution to brain Mn levels following inhalation exposure in the rat.

Administration, Inhalation↗
PubMed2002

Expression of netrin-1 and netrin-1 receptor, DCC, in the rat olfactory nerve pathway during development and axonal regeneration.

Netrin-1 is a bifunctional secreted protein that directs axon extension in various groups of developing axonal tracts. The transmembrane DCC (deleted in colorectal cancer) receptor is described as netrin-1 receptor and is involved in the attractive effects of netrin-1. In this study, we examined the spatio-temporal expression patterns of both netrin-1 and DCC in the rat olfactory system at different stages of development and during axonal regeneration following unilateral bulbectomy. High DCC expression was detected on the pioneer olfactory axons as they are extending toward the telencephalon. This expression was transient since from embryonic day 16 onwards, DCC was no longer detected along the olfactory nerve path. From embryonic day 14 until birth, DCC was also expressed within the mesenchyme surrounding the olfactory epithelium. During the same period, netrin-1 protein was detected along the trajectory of olfactory axons up to the olfactory bulb and its expression pattern in the nasal mesenchyme largely overlapped that of DCC. Moreover, netrin-1 continued to be present during the two first post-natal weeks, and a weak protein expression still persisted in the dorso-medial region of the olfactory epithelium in adult rats. While unilateral bulbectomy induced a transient up-regulation of netrin-1 in the lamina propria, particularly in the dorso-medial region of the neuroepithelium, no DCC expression was detected on the regenerating olfactory axons. In the developing olfactory bulb, the extension of mitral cell axons was associated with DCC presence while netrin-1 was absent along this axonal path. DCC was also highly expressed in the newly formed glomeruli after birth, and a weak DCC expression was still detected in the glomerular layer in adult rats. Taken together, these data support the notion that netrin-1, via DCC expressed on axons, may play a role in promoting outgrowth and/or guidance of pioneering olfactory axons toward the olfactory bulb primordium. Moreover, association of netrin-1 with mesenchymal DCC may provide a permissive environment to the growth of both pioneer and later-growing axons. The maintenance of netrin-1 expression in the nasal mesenchyme of adult rats as well as its regional up-regulation following unilateral bulbectomy infer that netrin-1, even in the absence of DCC, may be involved in the process of axonal growth of newly differentiated olfactory receptor neurons probably through the use of other receptors.

Animals↗
PubMed2003

Coordination of central odor representations through transient, non-oscillatory synchronization of glomerular output neurons.

At the first stage of processing in the olfactory pathway, the patterns of glomerular activity evoked by different scents are both temporally and spatially dynamic. In the antennal lobe (AL) of some insects, coherent firing of AL projection neurons (PNs) can be phase-locked to network oscillations, and it has been proposed that oscillatory synchronization of PN activity may encode the chemical identity of the olfactory stimulus. It remains unclear, however, how the brain uses this time-constrained mechanism to encode chemical identity when the stimulus itself is unpredictably dynamic. In the olfactory pathway of the moth Manduca sexta,we find that different odorants evoke gamma-band oscillations in the AL and the mushroom body (a higher-order network that receives input from the AL), but oscillations within or between these two processing stages are not temporally coherent. Moreover, the timing of action potential firing in PNs is not phase-locked to oscillations in either the AL or mushroom body, and the correlation between PN synchrony and field oscillations remains low before, during, and after olfactory stimulation. These results demonstrate that olfactory circuits in the moth are specialized to preserve time-varying signals in the insect's olfactory space, and that stimulus dynamics rather than intrinsic oscillations modulate the uniquely coordinated pattern of PN synchronization evoked by each olfactory stimulus. We propose that non-oscillatory synchronization provides an adaptive mechanism by which PN ensembles can encode stimulus identity while concurrently monitoring the unpredictable dynamics in the olfactory signal that typically occur under natural stimulus conditions.

Animals↗
PubMed1995

Analysis of chemical signals by nervous systems.

Intraspecific and interspecific communication and recognition depend on olfaction in widely diverse species of animals. Olfaction, an ancient sensory modality, is based on principles of neural organization and function that appear to be remarkably similar throughout the zoosphere. Thus, the "primitives" of olfactory stimuli that determine the input information of olfaction, the kinds of "molecular images" formed at various levels in the olfactory pathway, and the cellular mechanisms that underlie olfactory information processing are comparable in invertebrates and vertebrates alike. A case in point is the male-specific olfactory subsystem in moths, which is specialized to detect and analyze the qualitative, quantitative, and temporal features of the con-specific females' sex-pheromonal chemical signal. This olfactory subsystem can be viewed, and is here presented, as a model in which common principles of organization and function of olfactory systems in general are exaggerated to serve the requirements of a chemical communication system that is crucial for reproductive success.

Animal Communication↗
PubMed2001

Levels of dopamine in blood and brain following nasal administration to rats.

The aim of this study was to investigate the levels of [(3)H]dopamine in blood, the cerebrospinal fluid (CSF) and brain tissue samples in rats and to find out whether the drug is transferred along the olfactory pathway to the central nervous system following nasal administration. [(3)H]Dopamine (50 microCi) was given to male Sprague-Dawley rats either intravenously or nasally to the right nostril. For the absorption study, blood samples were withdrawn from the carotid artery. The CSF samples were taken by cisternal puncture and then brain tissue samples were excised. The presence of unchanged dopamine in the samples was ascertained using thin layer chromatography (TLC). The radioactivity in the samples was measured using liquid scintillation. The greatest amount of the total radioactivity absorbed from the nasal mucosa into the systemic circulation was observed at the first sampling point 15 min after administration. The bioavailability of the total radioactivity was 68+/-30%. The uptake of [(3)H]dopamine in the brain was significantly higher 30 min after nasal administration than after intravenous administration (P<0.01). TLC data showed that approximately 59%, 14% and 68% of the radioactivity in the olfactory bulb, CSF and olfactory mucosa, respectively, coeluted with dopamine. In conclusion, these results show that unchanged dopamine is transferred into the olfactory bulb via the olfactory pathway in rats.

Administration, Intranasal↗
PubMed2005

Chemosensory selectivity of output neurons innervating an identified, sexually isomorphic olfactory glomerulus.

The antennal lobe (AL) of insects, like the olfactory bulb of vertebrates, is characterized by discrete modules of synaptic neuropil called glomeruli. In some insects (e.g., moths and cockroaches), a few glomeruli are sexually dimorphic and function in labeled lines for processing of sensory information about sex pheromones. Controversy still exists, however, about whether projection (output) neurons (PNs) of glomeruli in the main AL are also narrowly tuned. We examined this critical issue in the AL of the moth Manduca sexta. We used intracellular recording and staining techniques to investigate the chemosensory tuning of PNs innervating an identifiable, sexually isomorphic glomerulus, G35, in the main AL. We found that the morphological features and chemosensory tuning of G35-PNs were nearly identical in females and males. G35-PNs responded to low concentrations of the plant-derived volatile compound cis-3-hexenyl acetate (c3HA), but the sensitivity threshold of female PNs was lower than that of male PNs. The propionate and butyrate homologs of c3HA could evoke excitatory responses but only at moderate-to-high concentrations. Other plant volatiles did not evoke responses from G35-PNs. Moreover, PNs innervating glomeruli near G35 (in females) showed little or no response to c3HA. Female G35-PNs were hyperpolarized by (+/-)linalool, a compound that excites PNs in an adjacent glomerulus, thus providing evidence for lateral-inhibitory interactions between glomeruli. Our results show that PNs arborizing in an identified glomerulus in the main olfactory pathway are morphologically and physiologically equivalent in both sexes and have characteristic, limited molecular receptive ranges that are highly conserved across individuals.

Acetates↗
PubMed2003

A diffusible signal attracts olfactory sensory axons toward their target in the developing brain of the moth.

The signals that olfactory receptor axons use to navigate to their target in the CNS are still not well understood. In the moth Manduca sexta, the primary olfactory pathway develops postembryonically, and the receptor axons navigate from an experimentally accessible sensory epithelium to the brain along a pathway long enough for detailed study of regions in which axon behavior changes. The current experiments ask whether diffusible factors contribute to receptor axon guidance. Explants were made from the antennal receptor epithelium and co-cultured in a collagen gel matrix with slices of various regions of the brain. Receptor axons were attracted toward the central regions of the brain, including the protocerebrum and antennal lobe. Receptor axons growing into a slice of the most proximal region of the antennal nerve, where axon sorting normally occurs, showed no directional preference. When the antennal lobe was included in the slice, the receptor axons entering the sorting region grew directly toward the antennal lobe. Taken together with the previous in vivo experiments, the current results suggest that an attractive diffusible factor can serve as one cue to direct misrouted olfactory receptor axons toward the medial regions of the brain, where local cues guide them to the antennal lobe. They also suggest that under normal circumstances, in which the receptor axons follow a pre-existing pupal nerve to the antennal lobe, the diffusible factor emanating from the lobe acts in parallel and at short range to maintain the fidelity of the path into the antennal lobe.

Animals↗