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Results for “Olfactory Pathways”

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At least 523 records · Page 29Linked to original sources
PubMed2006

Olfactory shifts parallel superspecialism for toxic fruit in Drosophila melanogaster sibling, D. sechellia.

Olfaction in the fruit fly Drosophila melanogaster is increasingly understood, from ligand-receptor-neuron combinations to their axonal projection patterns into the antennal lobe . Drosophila thus offers an excellent opportunity to study the evolutionary and ecological dynamics of olfactory systems. We compared the structure and function of the generalist D. melanogaster with that of specialist D. sechellia, which oviposits exclusively on morinda fruit . Our analyses show that whereas the fruit's headspace was dominated by acids, antennae responded most strongly to hexanoates. D. sechellia exhibited an extraordinarily strong response to methyl hexanoate (MeHex). Behaviorally, D. sechellia was much more attracted to these morinda fruit volatiles than was D. melanogaster. The high sensitivity to MeHex was paralleled by a 2.5x-3 x overrepresentation of MeHex neurons on the antenna and a concordant 2.9 x increase in volume of the corresponding glomerulus as compared to D. melanogaster. In addition, the MeHex neuron exhibited an extreme sensitivity down to femtograms of its ligand. In contrast, no peripherally mediated shift was found paralleling D. sechellia's increased attraction to acids. These findings are a demonstration of evolution acting at several levels in the olfactory circuitry in mediating a fruit fly's unique preference for fruit toxic to its sibling species .

Adaptation, Physiological↗
PubMed2006

Wiring specificity: axon-dendrite matching refines the olfactory map.

In Drosophila, about 50 classes of olfactory receptor neurons enter the brain where their axons form highly specific synapses with the dendrites of identified partner neurons. A recent study has shown that genetic manipulations that shift the position of one class of postsynaptic dendrites can cause an exact corresponding shift in the location of their partner axons.

Animals↗
PubMed2006

Intranasal immunization with inactivated tick-borne encephalitis virus and the antigenic peptide 89-119 protects mice against intraperitoneal challenge.

Detailed studies of the pathogenesis of certain neuroviral infections allow for a better understanding of the special role of the olfactory neuroepithelial cells in the invasion of viruses into the CNS. Several studies using animal models demonstrated that neurotropic viruses belonging to various families invade the brain via the olfactory tract after parenteral infection. We suppose that intranasal (i.n.) immunization inducing mucosal and systemic immunity will block neurotropic virus propagation into the brain via the olfactory pathway and neutralize virus multiplication in visceral organs. Subject of the present study was the efficacy of i.n. immunization of Balb/c mice with both killed tick-borne encephalitis (TBE) virus and antigenic peptide 89-119 from the envelope protein E of TBE virus in a nanoemulsion formulation. Intranasal immunization with nanoemulsion containing inactivated TBE virus particles induced specific both neutralizing and HAI antibodies. TBE virus specific IgA antibodies were detected in lung and nasal lavages of mice. The fourth i.n. immunization resulted in a drastic titer increase of the specific antibodies to 1:12,800, which was protective in all i.n. immunized mice against intraperitoneal (i.p.) challenge with 100 LD(50) of TBE virus. The ratio of specific IgG2a to IgG1 indicated the occurrence of a Th2 type immune response. We observed a similar balance of TBE virus-specific IgG2a/IgG1 after s.c. immunization of mice with the commercial FSME-Immun Inject vaccine against TBE virus. Thus, the experimental data obtained for the first time demonstrates the feasibility of using nanoparticles containing inactivated TBE virus for effective protection of i.n. immunized mice against the usually lethal infection. We analyzed a number of fragments of E protein of the TBE virus for antigenic similarity with human proteins by computer analysis. Local antigenic similarity of the fragments of E protein of TBE virus and human proteins allows for the identification of the epitopes, which may induce an autoimmune response if applied in a vaccine construct. One of the candidates, peptide 89-119 of E protein of the TBE virus does not contain any epitopes with local similarities to human protein epitopes. This peptide was synthesized and applied intranasally in nanoparticulate formulation. It induced TBE virus-specific antibodies and led to protection in the case of i.p. challenge with TBE virus.

Administration, Intranasal↗
PubMed2005

Maturation of odor representation in the honeybee antennal lobe.

The antennal lobe (AL) is the first center for processing odors in the insect brain, as is the olfactory bulb (OB) in vertebrates. Both the AL and the OB have a characteristic glomerular structure; odors sensed by olfactory receptor neurons are represented by patterns of glomerular activity. Little is known about when and how an odor begins to be perceived in a developing brain. We address this question by using calcium imaging to monitor odor-evoked neural activity in the ALs of bees of different ages. We find that odor-evoked neural activity already occurs in the ALs of bees as young as 1 or 2 days. In young bees, the responses to odors are relatively weak and restricted to a small number of glomeruli. However, different odors already evoke responses in different combinations of glomeruli. In mature bees, the responses are stronger and are evident in more glomeruli, but continue to have distinct odor-dependent signatures. Our findings indicate that the specific glomerular patterns for odors are conserved during the development, and that odor representations are fully developed in the AL during the first 2 weeks following emergence.

Acyclic Monoterpenes↗
PubMed2006

Manganese-enhanced 3D MRI of established and disrupted synaptic activity in the developing insect brain in vivo.

The antennal lobe of the sphinx moth Manduca sexta serves as a model for the development of the olfactory system. Here, the establishment of the glomerular synaptic network formed by the olfactory receptor axons and antennal lobe neurons at pupal stage P12 was followed by transection of the right antenna and - within 24 h - by injection of MnCl2 into the hemolymph. In vivo 3D MRI at 100 and 60 microm isotropic resolution was then performed at P13 to P17. Whereas the left antennal lobe revealed a pronounced increase of the signal-to-noise ratio (SNR) reflecting normal synaptic activity, the observation of only a small SNR increase within the right antennal lobe indicated the disruption of pertinent activity after antennal transection. The accumulation of manganese in the intact antennal system became observable within 3 h and lasted for at least 2 days after injection. Intra-individual comparisons between the right and left side yielded a statistically significant differential SNR increase in the left antennal lobe. Because such an effect was not observed in younger animals studied at pupal stages P10/P11, the MRI findings confirm the development of functional synapses in the antennal lobe of Manduca sexta by P13.

Animals↗
PubMed2004

The transcriptional repressor Mecp2 regulates terminal neuronal differentiation.

Rett syndrome (RTT) is a severe neurodevelopmental disorder with features of autism that results from mutation of the gene encoding the transcriptional repressor methyl-CpG binding protein (MECP2). The consequences of loss of a transcription factor may be complex, affecting the expression of many proteins, thus limiting understanding of this class of diseases and impeding therapeutic strategies. This is true for RTT. Neither the cell biological mechanism(s) nor the developmental stage affected by MECP2 deficiency is known. In vivo analysis of the olfactory system demonstrates that Mecp2 deficiency leads to a transient delay in the terminal differentiation of olfactory neurons. This delay in maturation disrupts axonal targeting in the olfactory bulb, resulting in abnormal axonal projections, subglomerular disorganization, and a persistent reduction in glomerular size. These results indicate a critical cell biological function for Mecp2 in mediating the final stages of neuronal development.

Animals↗
PubMed2005

Transient changes in the limbic histaminergic system after systemic kainic acid-induced seizures.

Increased brain histamine is reported to protect against convulsions. We used systemic kainic acid (KA) administration to study possible changes of the histaminergic system in rat brain in status epilepticus (SE). Robust increases in brain histamine concentrations and numbers of histamine-immunoreactive nerve fibers were detected in the piriform cortex (Pir) and amygdala after KA injection, suggesting a reactive increase, which is opposite to other published aminergic transmitter responses. These changes, lasting several weeks, might be coupled to a mechanism unrelated to the anticonvulsive function of histamine. Transient increases in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop, coupled to mitogen-activated protein kinase pathway, were detected first in the hippocampal CA3c area, followed by the Pir and amygdala and then the hippocampal CA1 area. These results suggest that histamine and H3 receptors, which also control the release of GABA and glutamate, might be involved in convulsive SE.

Amygdala↗
PubMed2006

First detection of olfactory marker protein (OMP) immunoreactivity in the olfactory epithelium of a cartilaginous fish.

Olfactory marker protein (OMP) is a protein expressed in the mature olfactory and vomeronasal neurons of many vertebrates, such as mammals, amphibians and bony fishes. Aim of this work was to investigate the OMP expression in the olfactory epithelium of the shark Scyliorhinus canicula (Linnaeus, 1758), by immunohistochemistry (IHC). Immunoreactivity was detected in the olfactory receptor neurons, in the crypt neurons and in the nerve fibers below the epithelium. Although very little is known about the OMP's function, its involvement in synaptogenesis, transduction cascade, neurogenesis and development of olfactory system has been suggested. The present work shows for the first time OMP's presence in a cartilaginous fish.

Animals↗
PubMed2006

Reproducibility of odor maps by fMRI in rodents.

The interactions of volatile odorants with the approximately 1000 types of olfactory receptor neurons in the olfactory mucosa are represented in the olfactory bulb by glomerular spatial activity maps. If these spatial maps underlie the perceptual identification of odorants then, for a given organism, they must be both specific and reproducible. However, this intra-organism reproducibility need not be present between organisms because genetic and developmental studies of olfactory bulb wiring suggest that there is substantial variation between the glomerular arrangements of closely related organisms and even between the two bulbs in a given animal. The ability of functional MRI (fMRI) to record responses of the entire rodent olfactory bulb repeatedly within the same subject has made it possible to assess the reproducibility of odor-induced spatial activity maps both within and between subjects exposed to equivalent stimuli. For a range of odorants, representing multiple chemical classes, a level of fMRI reproducibility (at 7.0 T and 9.4 T) comparable or superior to other cortical regions was demonstrated. While the responses of different bulbs to the same odorant could be localized within the same broad regions of the glomerular sheet, the precise magnitude and topology of the response within those regions were both often highly variable. These results demonstrate the robustness of high-field fMRI as a tool for assaying olfactory bulb function and provide evidence that equivalent perceptual outcomes may arise from divergent neural substrates.

Animals↗
PubMed2004

Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction.

Fruit flies are attracted by a diversity of odors that signal the presence of food, potential mates, or attractive egg-laying sites. Most Drosophila olfactory neurons express two types of odorant receptor genes: Or83b, a broadly expressed receptor of unknown function, and one or more members of a family of 61 selectively expressed receptors. While the conventional odorant receptors are highly divergent, Or83b is remarkably conserved between insect species. Two models could account for Or83b function: it could interact with specific odor stimuli independent of conventional odorant receptors, or it could act in concert with these receptors to mediate responses to all odors. Our results support the second model. Dendritic localization of conventional odorant receptors is abolished in Or83b mutants. Consistent with this cellular defect, the Or83b mutation disrupts behavioral and electrophysiological responses to many odorants. Or83b therefore encodes an atypical odorant receptor that plays an essential general role in olfaction.

Animals↗
PubMed2005

Drosophila OBP LUSH is required for activity of pheromone-sensitive neurons.

Odorant binding proteins (OBPs) are extracellular proteins localized to the chemosensory systems of most terrestrial species. OBPs are expressed by nonneuronal cells and secreted into the fluid bathing olfactory neuron dendrites. Several members have been shown to interact directly with odorants, but the significance of this is not clear. We show that the Drosophila OBP lush is completely devoid of evoked activity to the pheromone 11-cis vaccenyl acetate (VA), revealing that this binding protein is absolutely required for activation of pheromone-sensitive chemosensory neurons. lush mutants are also defective for pheromone-evoked behavior. Importantly, we identify a genetic interaction between lush and spontaneous activity in VA-sensitive neurons in the absence of pheromone. The defects in spontaneous activity and VA sensitivity are reversed by germline transformation with a lush transgene or by introducing recombinant LUSH protein into mutant sensilla. These studies directly link pheromone-induced behavior with OBP-dependent activation of a subset of olfactory neurons.

Action Potentials↗
PubMed2005

The molecular basis of odor coding in the Drosophila larva.

We have analyzed the molecular basis of odor coding in the Drosophila larva. A subset of Or genes is found to be expressed in larval olfactory receptor neurons (ORNs). Using an in vivo expression system and electrophysiology, we demonstrate that these genes encode functional odor receptors and determine their response spectra with 27 odors. The receptors vary in their breadth of tuning, exhibit both excitation and inhibition, and show different onset and termination kinetics. An individual receptor appears to transmit signals via a single ORN to a single glomerulus in the larval antennal lobe. We provide a spatial map of odor information in the larval brain and find that ORNs with related functional specificity map to related spatial positions. The results show how one family of receptors underlies odor coding in two markedly different olfactory systems; they also provide a molecular mechanism to explain longstanding observations of larval odor discrimination.

Animals↗
PubMed2005

Humans as an animal model for systems-level organization of olfaction.

The past 15 years have seen significant advances in the study of olfaction, with particular emphasis on elucidating the molecular building blocks of the sensory process. However, much of the systems-level organization of olfaction remains unexplored. Here, we provide an overview at this level, highlighting results obtained from studying humans, whom we think provide an underutilized, yet critical, animal model for olfaction.

Animals↗
PubMed2006

Strong single-fiber sensory inputs to olfactory cortex: implications for olfactory coding.

Olfactory information is first encoded in a combinatorial fashion by olfactory bulb glomeruli, which individually represent distinct chemical features of odors. This information is then transmitted to piriform (olfactory) cortex, via axons of olfactory bulb mitral and tufted (M/T) cells, where it is presumed to form the odor percept. However, mechanisms governing the integration of sensory information in mammalian olfactory cortex are unclear. Here we show that single M/T cells can make powerful connections with cortical pyramidal cells, and coincident input from few M/T cells is sufficient to elicit spike output. These findings suggest that odor coding is broad and distributed in olfactory cortex.

Action Potentials↗
PubMed2006

Odorant receptor map in the mouse olfactory bulb: in vivo sensitivity and specificity of receptor-defined glomeruli.

Odorant identity is represented in the olfactory bulb (OB) by the glomerular activity pattern, which reflects a combination of activated odorant receptors (ORs) in the olfactory epithelium. To elucidate this neuronal circuit at the molecular level, we established a functional OR identification strategy based on glomerular activity by combining in vivo Ca(2+) imaging, retrograde dye labeling, and single-cell RT-PCR. Spatial and functional mapping of OR-defined glomeruli revealed that the glomerular positional relationship varied considerably between individual animals, resulting in different OR maps in the OB. Notably, OR-defined glomeruli exhibited different ligand spectra and far higher sensitivity compared to the in vitro pharmacological properties of corresponding ORs. Moreover, we found that the olfactory mucus was an important factor in the regulation of in vivo odorant responsiveness. Our results provide a methodology to examine in vivo glomerular responses at the receptor level and further help address the long-standing issues of olfactory sensitivity and specificity under physiological conditions.

Animals↗
PubMed2007

Semaphorin-1a controls receptor neuron-specific axonal convergence in the primary olfactory center of Drosophila.

In the olfactory system of Drosophila, 50 functional classes of sensory receptor neurons (ORNs) project in a highly organized fashion into the CNS, where they sort out from one another and converge into distinct synaptic glomeruli. We identified the transmembrane molecule Semaphorin-1a (Sema-1a) as an essential component to ensure glomerulus-specific axon segregation. Removal of sema-1a in ORNs does not affect the pathfinding toward their target area but disrupts local axonal convergence into a single glomerulus, resulting in two distinct targeting phenotypes: axons either intermingle with adjacent ORN classes or segregate according to their odorant receptor identity into ectopic sites. Differential Sema-1a expression can be detected among neighboring glomeruli, and mosaic analyses show that sema-1a functions nonautonomously in ORN axon sorting. These findings provide insights into the mechanism by which afferent interactions lead to synaptic specificity in the olfactory system.

Animals↗
PubMed2004

The central piriform cortex: anatomical connections and anticonvulsant effect of GABA elevation in the kindling model.

The piriform cortex (PC) is thought to be critically involved in the generation and propagation of forebrain (limbic type) seizures in the rat. The PC extends over a large area at the ventrolateral side of the rat brain with an anterior part highly sensitive for bicuculline-induced and a central part most sensitive for electrically induced seizures. Therefore, distinct parts of the PC might be differentially involved in the generation and spread of seizure activity. Since previous studies indicated that a loss of GABAergic inhibition in the PC is involved in the generation of epileptic activity, we microinjected the GABA-transaminase blocker vigabatrin bilaterally in the anterior, central and posterior PC of previously amygdala-kindled rats and repeatedly tested its effect on kindled seizures. Vigabatrin was anticonvulsant in all groups for up to 13 days with a maximal effect 24 h after injection. However, the anticonvulsant effect on seizure generalization was strongest after microinjection in the central PC suggesting that GABAergic synapses in this part are critically involved in the development of generalized seizures. Since differences in anatomical connections of the PC regions may be responsible for differences in seizure susceptibility, we addressed this question by injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin in different PC subregions. Although there were similarities in the projections from different PC subregions, we also found differences between the PC subregions in their projections to structures known to be important in the limbic seizure network, such as the perirhinal cortex, nucleus accumbens, and striatum. These differences in anatomical connectivity between PC subregions may be involved in the differences in seizure susceptibility observed in the present and previous studies.

Animals↗
PubMed2005

Ciliary neurotrophic factor-immunoreactivity in olfactory sensory neurons.

Ciliary neurotrophic factor (CNTF) has been implicated in processes of neuroprotection, axonal regeneration and synaptogenesis in the lesioned CNS. In the olfactory system, which is characterized by particularly robust neuroplasticity throughout life, the concentration of CNTF is high even under physiological conditions. In the present study, the cellular localization of CNTF-immunoreactivity was studied in the rat and mouse olfactory epithelium. In both species, individual olfactory sensory neurons (ONs) displayed intense CNTF-immunoreactivity. The number of CNTF-ir ONs varied interindividually in rats and was lower in mice than in rats. In olfactory epithelia of mice expressing beta-galactosidase under control of the CNTF promoter, cells of the ON layer were immunoreactive for the reporter protein. CNTF-ir ONs were olfactory marker protein-positive and growth associated protein 43-negative. CNTF-ir ONs lacked apoptotic markers, and the number of specifically labeled ONs was apparently unchanged after light chemical lesioning of the epithelium, indicating that CNTF-immunoreactivity was not associated with ON death. Electron microscopy of CNTF-ir ON axons in innervated olfactory bulb glomeruli documented that they formed typical ON axonal synapses with target neurons. Three dimensional reconstructions of bulb pairs showed a striking similarity of the positions of glomeruli innervated by CNTF-ir ON axons in left and right bulbs of individual animals and interindividually. The number of innervated glomeruli differed interindividually in rats and was lower in mice than in rats. The results show that in rodents CNTF-immunoreactivity occurs in a subset of mature, functionally competent ONs. The localization of target glomeruli suggests that CNTF-immunoreactivity may be associated with the expression and/or activation of specific olfactory receptor proteins.

Animals↗