bluuebunny/crossref_metadata_2025 huggingface dataset:
Proliferation Decrease in the Olfactory Epithelium during Postnatal Developmenta
Authors: WEILER ELKE , FARBMAN ALBERT I.
Published: February 2006

ABSTRACT: Olfactory sensory cells are replaced continuously throughout the life of an animal. In postnatal rats proliferation density decreases dramatically, and continues to decrease into adulthood at least up to 11 months of age. This is true in both the basal cell and supporting cell populations. However, correlation analysis revealed there was no correlation in mitotic rate between the two cell types, suggesting that proliferation of the two cell types is regulated differently. With age, the rat body size and the area covered by olfactory epithelium increases. We present evidence that supporting cell proliferation provides only for growth, whereas proliferation of basal cells provides for both growth and replacement. Further, we present evidence that in older animals the sensory cells live longer than they do in younger animals.
Effects of Insulin‐Like Growth Factor 1 on Olfactory Neurogenesis In Vivo and In Vitroa
Authors: PIXLEY SARAH K. , DANGORIA NANDITA S. , ODOMS KELLI K. , HASTINGS LLOYD
Published: February 2006

ABSTRACT: The rate of neurogenesis in the peripheral olfactory neuroepithelium is regulated by unknown mechanisms. The members of the insulin‐like growth factor (IGF) family can influence neuronal generation, survival and/or differentiation. Several members of this family, in particular IGF‐1, are expressed at high levels in the olfactory bulb and epithelium, where they could influence the generation and/or survival of olfactory receptor neurons (ORNs). To explore the role of IGF‐1 in the olfactory epithelium (OE), we asked which cells expressed IGF‐1 receptors (IGF‐1Rs), using olfactory cell cultures and cryostat‐cut tissue sections of neonatal (postnatal day four) and adult rat OE. An antibody specific for the a subunit of the IGF‐1R densely labeled a subset of ORNs but not other cell types in sections and cultures. These ORNs were primarily immature, as determined by double labeling with neuronal markers. The number of IGF‐1R‐labeled cells as well as the levels of IGF‐1R protein (determined by immunoprecipitation and Western blotting) decreased with age, which is consistent with normal developmental changes. To study IGF‐1 effects in the intact animal, we infused IGF‐1 and related growth factors into the noses of newborn Sprague‐Dawley rats, i.e., when the epithelium is still developing. Growth factors or carrier solution (0.9% NaCl with 0.25% bovine serum albumin to prevent nonspecific binding) were applied (10 ml) to the left nostril once per day starting shortly after birth on postnatal day 1 (P1), P2 and P3, and the animals were sacrificed on P4 by decapitation. After paraformaldehyde immersion fixation, cryostat sections of the olfactory area of the nose were immunostained for the proliferating cell nuclear antigen (PCNA). Sections were position‐matched by turbinate structure and then epithelial height and area of PCNA staining at the base of the epithelium (which represents division of primarily neuronal precursors) were measured by image analysis. Both were significantly increased by rat IGF‐1 (20 ng/ml, 2.6 nM), but not insulin (20 ng/ml, 2.6 nM) or an IGF‐1 derivative, LongR3 1GF‐1 (200 ng/ml, 22 nM), that does not bind to the IGF‐1 binding proteins (IGFBPs). Thus IGF‐1 appears to influence the rate of olfactory neurogenesis, and its actions are not modified by the IGFBPs. These data suggest an important role for IGF‐1 in the OE.
Does Olfactory Marker Protein Participate in Olfactory Neurogenesis?a
Authors: FARBMAN ALBERT I. , BUCHHOLZ JUDITH A. , WALTERS ERIC , MARGOLIS FRANK L.
Published: February 2006

ABSTRACT: Olfactory marker protein (OMP) is a phylogenetically conserved, 19‐kDa, acidic, soluble protein found abundantly in mature olfactory sensory neurons. Its function has been enigmatic although recent evidence from studies on OMP null mice suggests that neurons lacking OMP exhibit altered physiological activity, including prolonged onset and recovery kinetics following stimulation.2 We have reported increased expression of OMP in individual surviving sensory neurons that have been deprived of their target, the olfactory bulb.3 Because olfactory epithelia deprived of their target also exhibit an increased rate of cell division we investigated the effect of recombinant OMP on cell division in organotypic cultures of fetal rat (embryonic day 19) epithelium grown for 3 days in vitro. After 3 days, cultures were given a 1‐hr pulse of a mitotic marker, bromodeoxyuridine (BrdU), fixed and prepared for immunohistochemistry to determine the number of proliferating cells. We found a dose‐dependent increase in the number of BrdU‐positive cells/100‐mm length of epithelium. The number of labeled cells increased incrementally, reached a plateau at 25 pM OMP/ml culture medium, 50% higher than in cultures with no OMP added, and remained at that level at 50 and 100 pM doses. Controls included trypsinized OMP and addition of equivalent volumes of TRIS buffer lacking OMP. These results, taken together with previous studies on several growth factors5 indicate that regulation of neurogenesis in olfactory tissue is a multifactorial process and that OMP may play a role.
Cell Death, Phagocytosis, and Neurogenesis in Mouse Olfactory Epithelium and Vomeronasal Organ after Colchicine Treatment
Authors: SUZUKI YUKO
Published: February 2006

ABSTRACT: The cytotoxic agent colchicine induced apoptotic cell death in the mouse olfactory epithelium and vomeronasal organ. The terminal deoxynucleotidyl transferase‐mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) method revealed the presence of many apoptotic bodies in the middle to basal region of the septal olfactory epithelium and vomeronasal organ near the boundary of the respiratory epithelium at 1 day after intraperitoneal (i.p.) injection of colchicine (4 mg/kg). In some areas of the nasal turbinates, massive apoptosis was observed in the olfactory epithelium. Electron micrographs showed that immature olfactory cells and globose basal cells were killed by the colchicine and had been phagocytized by the suppor ting cells and macrophages. In some areas of the nasal turbinates, mature olfactory cells were also killed, and thus only the supporting cells and horizontal basal cells remained in the epithelium. Bromodeoxyuridine (BrdU) labeling showed that regeneration occurred in the septum and vomeronasal organ at 4‐6 days after colchicine treatment; however, there were no regenerated olfactory cells in some areas of the turbinates up to 30 days after colchicine treatment.
ErbB‐3 and ErbB‐4 Expression in the Mouse Olfactory Systema
Authors: PERROTEAU ISABELLE , OBERTO MICHELA , IERACI ALESSANDRO , BOVOLIN PATRIZIA , FASOLO ALDO
Published: February 2006

ABSTRACT: The interplay between neuregulins and the ErbB receptor family has a pivotal role in the development of several tissues, including the nervous system, and is maintained in the adult olfactory system where extensive plasticity and neurogenesis are retained. In the present work we show the immunohistochemical localization of ErbB‐3 and ErbB‐4 in the olfactory system of adult normal and lesioned mice. The expression of ErbB‐3 is demonstrated to be restricted to the ensheathing cells of the olfactory nerve and to a few substentacular cells of the olfactory epithelium (OE). ErbB‐3 staining circumvents the glomeruli but is never observed inside them or elsewhere in the adult olfactory bulb. Conversely, ErbB‐4 immunoreactivity is found in all the periglomerular and mitral/tufted cells of the olfactory bulb (OB) and to a minor extent in the olfactory neurons and basal cells of the OE. Interestingly enough, cells coming out from the rostral migratory stream of the subependymal layer (SEL), as well as isolated cells in the granule cell layer, possibly migrating cells, strongly stained for ErbB‐4 expression. Lesions of the olfactory epithelium have been performed by unilateral intranasal irrigation with ZnSO4 and 3 weeks after the irrigation, the olfactory bulbs were analyzed for olfactory marker protein (OMP), tyrosine hydroxylase (TH), ErbB‐3 and ErbB‐4 expression. In the deafferented OB, the drastic loss of immunoreactivity for OMP was accompanied by a strong reduction of ErbB‐3 expression. Most of the deafferented dopaminergic interneurons switched off TH expression. In the deafferented periglomerular and mitral/tufted cells ErbB‐4 expression was turned off and down, respectively. No differences were noted at the granular cell layer level in the deafferented OB with respect to control. Taken together our results suggest that, in normal conditions, neuregulins are involved in the survival of the ensheathing cells of the olfactory nerve through ErbB‐3 activation and in the functional activity of postsynaptic neurons through ErbB‐4 activation.
The Influence of Ensheathing Cells on Olfactory Receptor Cell Neurite Outgrowth In Vitroa
Authors: KAFITZ KARL W. , GREER CHARLES A.
Published: February 2006

ABSTRACT: We previously reported that laminin substrates increased primary (1°) neurite outgrowth from olfactory receptor cells (ORCs) in vitro.5 To further explore mechanisms underlying the outgrowth of ORC neurites, we have cocultured ORCs with the ensheathing cells (ENSH) from the olfactory nerve.

ORCs were plated either: (i) directly on monolayers of ENSH (prepared with minor modifications as reported by Doucette and Devon,8 or (ii) on coverslips suspended above the ENSH monolayer to investigate diffusible trophic influences of ENSH. In addition, ORCs were cocultured with either olfactory bulb glia (OBG) or hippocampal astrocytes (HG) or grown on either laminin (LN) substrates or poly‐l‐lysine (PLL) controls. The length of ORC neurites was determined after 48 hr in vitro. Immunocytochemical characterization of the ENSH cultures for p75 nerve growth factor (NGF) receptor and glial fibrillary acidic protein (GFAP) revealed that those cultures contained more than 80% ENSH. In OBG cultures ~10% and in HG cultures no cells with ENSH characteristics were found. All cells with ENSH characteristics were also LN‐immunoreactive. After 48 hr in culture ORCs had the longest 1° neurites when they were cocultured with ENSH. No significant differences in the 1° neurite length were found comparing ORCs grown directly on ENSH and ORCs physically separated from ENSH. ORCs cultured on HG and on EHS‐LN showed no significant differences in the ORC 1° neurite length, but on both substrates the ORC 1° neurites were significantly shorter than on ENSH. The length of the ORC secondary neurites did not vary significantly in the different culture conditions. Our results suggest that while LN appears to contribute to ORC neurite extension, additional diffusible factors released from ENSH are likely to be further determinants of neurite outgrowth. Because the OBG and HG cocultures did not influence ORC neurite outgrowth as significantly as did the ENSH, it seems plausible to suggest that these diffusible factors may be specific to subpopulations of glial cells.
Addition of New Cells to the Olfactory Bulb of Adult Zebrafisha
Authors: BYRD CHRISTINE A. , BRUNJES PETER C.
Published: February 2006

ABSTRACT: We have been examining patterns of cell proliferation in the brain of adult zebrafish. Understanding this process in fish may lead to important insights due to the tremendous regenerative capabilities of these animals. Fish were exposed to a 1% solution of the thymidine analog 5‐bromo‐2′‐deoxyuridine (BrdU) for 1 hr before being returned to small aquaria that received frequent water changes. Animals were overanesthetized and perfused with Bouin's fixa tive solution after two survival periods (4 hr or 3‐4 weeks). Paraffin immunohistochemistry using a monoclonal antibody against BrdU was used to visualize the newly generated cells. Quantitative analyses were performed on serial, 10‐mm sections from 4 animals for each survival group. Statistical determinations were based on the nonparametric Mann‐Whitney U test. The ave rage number of BrdU‐labeled nuclear profiles in the bulbs, from analysis of every 5th section, was significantly different between the two groups (22.0 ± 6.8 [SEM] for the 4‐hr group and 136.7 ± 11.3 for the 4‐wk group; p < 0.05). The volumes of the bulbs, however, were not different between the two groups (p > 0.5). These data indicate that either cells divided repeatedly during the longer survival period or cells migrated into the bulb from other brain regions. To examine this phenomenon further, the location of the new cells was analyzed in three mid‐bulb sections (20 μm apart) from each animal. Both the area and number of labeled nuclei in each lamina were measured to obtain an average profile density. Comparison of the 4‐hr and the 4‐wk groups showed that density was significantly greater in all bulb layers in the long survival group (p < 0.05 for all). In the 4‐hr survival group, cells were found mainly in the olfactory nerve layer. When examined after 4 wk, proportionately more labeled cells were found in the internal cell layer. This addition of new cells could be a result of neurogenesis, gliogenesis, and/or angiogenesis. We are currently performing double‐labeling experiments to determine the types of cells that are added to the adult bulb. In addition, our future plans include investigating the origin of these cells and the signals that direct their formation.
Odorant‐Binding Proteins: Structural Aspects
Authors: PELOSI PAOLO
Published: February 2006

ABSTRACT: Structural data on odorant‐binding proteins (OBPs), both in vertebrates and in insects, are reviewed and discussed. OBPs are soluble proteins interacting with odor molecules and Pheromones in the perireceptor areas, the nasal mucus in vertebrates and the sensillar lymph in insects. The physiological function of these proteins is still uncertain, but information on their structure is abundant and accurate. Based on complete amino acid sequences, several subclasses have been identified, suggesting a role in odor discrimination. The OBPs of vertebrates belong to the family of lipocalins that includes proteins involved in the delivery of pheromonal messages. Those of insects do not bear significant similarity to any other class of proteins. The three‐dimensional structure of the bovine OBP is a β‐barrel, while for insect OBPs a model has been proposed, mainly containing α‐helix motifs. In some cases the amino acid residues involved in ligand binding have been identified with the use of photoaffinity label analogues.
Evolution of Olfactomedin: Structural Constraints and Conservation of Primary Sequence Motifs
Authors: KARAVANICH CHRISTY , ANHOLT ROBERT R.H.
Published: February 2006

ABSTRACT: Olfactomedin is a glycosylated extracellular matrix protein originally identified at the mucociliary surface of the amphibian olfactory neuroepithelium and subsequently localized throughout the mammalian central nervous system. Although olfactomedin homologues have been identified in fish, frog, rat, mouse and human, its function is still unknown. As a first step toward elucidating the function of olfactomedin, sequences of teleost, amphibian and human homologues were compared to identify invariant, and hence, potential functionally important motifs. Previous studies revealed 33% amino acid sequence identity between rat and frog olfactomedin in their carboxyl terminal segments.3 Further analysis, however, reveals more extensive homologies throughout the molecule. Despite significant sequence divergence, cysteines essential for homo‐polymer formation, such as the CXC motif near the amino terminus, are conserved as is the characteristic glycosylation pattern, suggesting that these posttranslational modifications are essential for function. Furthermore, alignment of a region of 53 amino acids of fish, frog, rat and human olfactomedin reveals seven invariant residues including a negatively charged cluster of aspartic and glutamic acid residues. Molecular evolutionary genetic analysis reveals an accelerated rate of nucleotide substitutions in the mammalian lineage. The evolutionary rate at the protein level, however, is constant, indicating that evolution of olfactomedin is constrained by structural limitations. Whereas considerable evolutionary divergence is evident between fish, frog and mammalian olfactomedins, olfactomedins of rat and human show 98% amino acid sequence identity. It appears that an ancestral olfactomedin gene arose before the evolution of terrestrial vertebrates and evolved independently in teleost, amphibian and mammalian lineages. The apparent evolutionary pressure toward conservation of primary structure supports the notion that olfactomedin has an important function in the mammalian nervous system.
Pheromone‐Binding Proteins of Scarab Beetlesa
Authors: LEAL WALTER SOARES , WOJTASEK HUBERT , MIYAZAWA MITSUHIRO
Published: February 2006

ABSTRACT: We have characterized Pheromone binding proteins (PBPs) present in the antennae of several species of scarab beetles. In most cases there was only one class of PBP, which was expressed in both sexes. Both Anomala osakana and Popillia japonica possess a single PBP, highly homologous to each other. In each species the same PBP seems to recognize both enantiomers of japonilure, which have opposite biological functions, i.e., the sex Pheromone and the behavioral antagonist (stop signal). The purified PBP of A. osakana binds both enantiomers apparently with the same low affinity. Unexpectedly, these ligands were bound by moth PBPs, which utilize Pheromones with unrelated structures. These findings suggest that the ligand specificity in this class of proteins may not be as high as it has been postulated.
Odorant‐Binding Proteins of True Bugs: Generic Specificity, Sexual Dimorphism, and Association with Subsets of Chemosensory Sensilla
Authors: DICKENS JOSEPH C. , CALLAHAN FRANKLINE E. , WERGIN WILLIAM P. , MURPHY CHARLES A. , VOGT RICHARD G.
Published: February 2006

ABSTRACT: Odorant‐binding proteins (OBPs) in insects occur within olfactory sensilla, and are thought to transport chemical stimuli to receptors on dendrites of sensory neurons. Until recently, knowledge of OBPs in insects was limited to moths and Drosophila. We discovered an antennal‐specific protein (Lygus [lineolaris] antennal protein, LAP) with a unique N‐terminal sequence in the true bug, Lygus lineolaris. We localized LAP to antennae, determined its molecular weight (16 kDa), and showed that while it was expressed in nymphal antennae, its levels dramatically increased in adults concurrent with increases in numbers of olfactory sensilla and electrical responses to odors. In our current study, we used immunological techniques to demonstrate in more detail that LAP occurs only in antennae, and to show its expression within Lygus species. LAP was expressed more in male antennae than in antennae of females for the Lygus species examined. Anti‐LAP did not recognize antennal proteins of two other genera of bugs. Immunocytological studies showed LAP primarily within the sensillar lymph of type 1 and type 4 sensilla on antennae. These observations strongly suggest LAP to be an OBP, and our discovery and characterization of OBPs in true bugs provides a third order for use in the study of evolution of OBPs in insects.
Olfactory Coding in a Compound Nose: Coexpression of Odorant‐Binding Proteins in Drosophilaa
Authors: HEKMAT‐SCAFE DARIA S. , STEINBRECHT R. ALEXANDER , CARLSON JOHN R.
Published: February 2006

ABSTRACT: Odorant‐binding proteins (OBPs) are small, soluble proteins present in the aqueous medium surrounding olfactory receptor neurons. Their function in olfaction is unknown: they have been proposed to facilitate the transit of hydrophobic molecules to olfactory receptors, to deactivate the odorant stimulus, and/or to play a role in chemosensory coding. We have examined the genomic organization and expression patterns of two olfactory‐specific genes (OS‐E and OS‐F) of Drosophila melanogaster, the products of which are members of a protein family in Drosophila sharing sequence similarity with moth OBPs. We found that the OS‐E and OS‐F transcription units are located <1 kb apart. They are oriented in the same direction and display a similar intron‐exon organization. Expression of both OS‐E and OS‐F proteins is spatially restricted to the ventro‐lateral region of the Drosophila antenna. Within this region, both OS‐E and OS‐F proteins are expressed within two different types of sensory hairs: in most, if not all, sensilla trichodea and in ∼40% of the interspersed small sensilla basiconica. We consistently observe that OS‐E and OS‐F are coexpressed, indicating that an individual sensillum can contain more than one odorant‐binding protein. This finding has potential implications for the roles of odorant‐binding proteins in olfactory coding.
A Quantitative Model of Odor Deactivation Based on the Redox Shift of the Pheromone‐Binding Protein in Moth Antennae
Authors: KAISSLING KARL‐ERNST
Published: February 2006

ABSTRACT: Recent in vitro experiments with homogenates of isolated olfactory hairs of Antheraea polyphemus suggest that the Pheromone‐binding protein (PBP) is involved not only in Pheromone solubilization and transport but also in Pheromone deactivation.1 PBP occurs in a reduced form with one or two disulfide bridges (PBPred) and in the oxidized form with three bridges (PBPox). From kinetic experiments it was concluded that the Pheromone is first bound to PBPred. This complex activates the receptor molecules and then turns into the oxidized form which‐according to our working hypothesis‐is unable to activate further receptor molecules.1 Apparently, the Pheromone bound to the PBP (both forms) is protected from enzymatic degradation into nonexcitatory metabolites.2 A quantitative kinetic model of Pheromone deactivation was developed (in collaboration with J. Thorson, Oxford) in which the receptor molecules are considered to act as enzymes catalyzing the redox shift of the binding protein.
Odorant‐Binding Proteins: Expression and Function
Authors: STEINBRECHT RUDOLF ALEXANDER
Published: February 2006

ABSTRACT: Odorant‐binding proteins (OBPs) are a major constituent of the aqueous perireceptor compartment in vertebrates and in insects. Although different in primary structure, they are supposed to serve similar functions in both animal groups: (i) OBPs may act as solubilizers and carriers of the lipophilic odorants in the aqueous mucus or sensillum lymph; (ii) OBPs may act in addition as peripheral filters in odor discrimination by selectively binding certain classes of odorants; (iii) OBPs may present the stimulus molecule in a particular way to the receptor proteins to facilitate signal transduction; (iv) OBPs may clean the perireceptor space from unwanted and toxic compounds; (v) OBPs may rapidly deactivate odorants after stimulation of the receptors. Experimental evidence in favor of this multiple role of OBPs is reviewed.
Pheromones, the Vomeronasal System, and Communication: From Hormonal Responses to Individual Recognition
Authors: Johnston Robert E.
Published: February 2006

ABSTRACT: The functions of the vomeronasal and olfactory systems are evaluated within the broad context of chemical communication in mammals. Five main points are stressed. First, there are a variety of types of chemical signals, ranging from classic Pheromones to odor quality signals, all of which are important for communication. Second, the vomeronasal organ is primarily responsible for mediating responses to some, but by no means all, Pheromone‐like signals. Third, the olfactory system mediates responses to some Pheromone‐like signals. Fourth, the vomeronasal system mediates some responses to odor quality signals. Thus, not all receptors in the vomeronasal organ are involved in detection of Pheromones. Fifth, the vomeronasal and olfactory systems often interact to mediate responses to odor signals. In sum, it is important to maintain a broad, balanced view and to avoid oversimplifications if we are to advance our understanding of the sensory mechanisms underlying responses to chemical signals and other odors.
Integration of Chemosensory and Hormonal Input in the Male Syrian Hamster Brain
Authors: WOOD RUTH I.
Published: February 2006

ABSTRACT: Mating in the male Syrian hamster requires the interaction of chemosensory and hormonal stimuli. Chemosensory cues from the vomeronasal organ and olfactory mucosa are transmitted through limbic nuclei that contain receptors for gonadal steroid hormones, including the medial amygdaloid nucleus (Me) and medial preoptic area (MPOA). This pathway is essential for mating, as lesions that interrupt transmission of chemosensory cues to MPOA will abolish copulation. Likewise, gonadal steroids facilitate sexual behavior through Me and MPOA, as demonstrated using intracranial implants in the brains of castrate males. In addition, odor and hormonal signals must be integrated in the brain for copulation to occur. Mating is prevented when olfactory bulbectomy is performed ipsilateral to an intracranial testosterone implant, thereby preventing the interaction of odors and hormones. According to our current model, hormones may act as a gating signal to strengthen synaptic contacts along the chemosensory pathway, thereby permitting or enhancing transmission of chemosensory cues.
On the Nature of Mammalian and Human Pheromones
Authors: McCLINTOCK MARTHA K.
Published: February 2006

ABSTRACT: Communication by chemical (Pheromone) signals is important in many species, including mammals. Chemosensory and hormonal systems can interact in at least two ways: (i) chemosensory input, especially but not exclusively that through the vomeronasal organ, may elicit hormonal release, which, in turn, may facilitate behavioral or physiological responses; and (ii) hormones, especially steroids, may be essential for some responses to chemosensory, including vomeronasal, input. Recent, still controversial reports, suggest that chemosensory communication may occur in humans via a residual vomeronasal organ and that chemosensory/hormonal interactions also operate in humans.

In this symposium these matters are examined critically. Johnston explores the concept of Pheromone communication and suggests that the notion of a single‐chemical 'magic bullet' irresistably leading to a preprogrammed result is too simplistic despite documented examples of special stimuli acting via the vomeronasal organ. Meredith briefly reviews evidence for hormonal mediation of the effects of vomeronasal input; including a situation where vomeronasal and hormonal facilitation of a behavior appear to be interchangable‐but where vomeronasal input appears important only in inexperienced animals. Wood discusses evidence that the effectiveness of chemosensory input to particular brain nuclei depends critically on the simultaneous presence of a steroid hormone within the same nucleus. Monti‐Bloch presents his evidence that steroids may act as gender‐specific chemical signals in humans, exciting an electrical response from the residual human vomeronasal organ and affecting human hormone levels.
Introductory Remarks on Umami Taste
Authors: KURIHARA KENZO , KASHIWAYANAGI MAKOTO
Published: February 2006

ABSTRACT: Psychophysical and electrophysiological studies indicated that the umami substances have no enhancing activity on other primary tastes. Experiments using amiloride clearly show that the umami component of canine chorda tympani nerve response to umami substances is independent of the salt component. Single fiber analysis of the responses of the mouse glossopharyngeal nerve and the monkey primary taste cortex neuron show that the responses to umami substances are independent of other primary tastes. A large synergism between monosodium glutamate (MSG) and disodium 5'‐inosinate (IMP) or disodium 5′‐guanylate (GMP) is observed in dogs and is explained in terms of allosteric effect. The order of intensity of umami taste induced by a mixture of 0.5 mM GMP and 1.5 mM of various agonists for the glutamate receptors was glutamate>ibotenate>dl(+)‐2‐amino‐4‐phosphonobutyric acid (DL‐AP4)‐(+)‐1‐aminocyclopentane‐trans‐1,3‐dicarboxylic acid (trans‐ACPD). Kainate, N‐methyl‐d‐aspartate (NMDA) and (RS)‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA), which are agonists for ionotropic receptors, have no umami taste. It was concluded that the umami receptor is not identical to any of known glutamate receptors, and there seems to be a unique receptor for umami.
Molecular and Physiological Evidence for Glutamate (Umami) Taste Transduction via a G Protein‐Coupled Receptora
Authors: CHAUDHARI NIRUPA , ROPER STEPHEN D.
Published: February 2006

ABSTRACT: Recent molecular analyses have demonstrated that a metabotropic glutamate receptor, mGluR4, is expressed in taste buds from rat circumvallate and foliate papillae. Behavioral studies demonstrated that l(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4), an agonist for mGluR4 and related receptors, mimics the taste of monosodium glutamate (MSG) in rats. mGluR4 is known to signal through inhibition of the cyclic adenosine‐5′,3′‐monophosphate (cAMP) cascade. Circumvallate and foliate taste buds exhibit decreases of cAMP levels following stimulation with MSG, and the response is potentiated by 5′‐inosine monophosphate, suggesting that it is related to umami taste. Further, experiments on mice with the mGluR4 gene knocked out support the interpretation that mGluR4 is a key component in glutamate taste. Glutamate may also stimulate taste buds through an ionotropic receptor pathway. In patch‐clamp studies, glutamate evokes two types of currents, similar to those elicited by N‐methyl‐d‐aspartate (N MDA) and L‐AP4. We speculate upon the significance of two glutamate receptor pathways in taste buds.
Responses to Monosodium Glutamate and Guanosine 5′‐Monophosphate in Rat Fungiform Taste Cellsa
Authors: Lin W. , Kinnamon S. C.
Published: February 2006

ABSTRACT: Monosodium glutamate (MSG) elicits a unique taste sensation called umami. The umami sensation is potentiated by the presence of 5′‐ribonucleotides such as guanosine 5′‐monophosphate (5′‐GMP). We have used giga‐seal whole cell recording to examine glutamate transduction in individual cells of isolated rat fungiform taste buds. Approximately 56% of fungiform taste cells responded to bath application of glutamate. Three types of responses occurred: decrease in inward holding current; increase in inward holding current; and a biphasic response, with an increase followed by a decrease in holding current. Similar responses were observed in response to 5′‐GMP. Further, responses to 5′‐GMP may occur in cells that are glutamate‐insensitive, suggesting that different receptors mediate the transduction of glutamate and 5′‐GMP. Simultaneous bath application of glutamate and 5′‐GMP resulted in a synergistic response in some taste cells.
The Neurophysiology of Taste and Olfaction in Primates, and Umami Flavora
Authors: ROLLS EDMUND T. , CRITCHLEY HUGO D. , BROWNING ANDREW , HERNADI ISTVAN
Published: February 2006

ABSTRACT: To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5′‐monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases this reduction was sensory‐specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.
Effects of Monosodium Glutamate on Human Food Palatabilitya
Authors: Bellisleb FRANCE
Published: February 2006

ABSTRACT: Monosodium glutamate (MSG) is a well‐known flavor enhancer used in both Western and Eastern cuisines. Responsible for the 'umami' (delicious) taste, it is incorporated into a large number of solid and liquid savory foods. Experimental studies have established that the presence of added MSG in foods influences palatability, preference and selection. Sensory evaluation tests have shown that both traditional and novel foods get higher palatability ratings if MSG is added at an appropriate dose. In young adults, behavioral tests have shown that the acquisition of a liking for novel foods is facilitated by the addition of MSG to the recipe. In institutionalized elderly persons as well as hospitalized diabetic patients, the addition of MSG to target foods in a lunch meal induced an increased intake for those specific foods, with a subsequent decreased intake of foods presented later in the meal. In both populations, only prandial food selection was affected by MSG, but meal size (kJoules) remained the same. Experiencing the positive effects of MSG is thus possible without inducing hyperphagia. In conclusion, MSG can be used casually by the consumer in order to increase palatability, and it can also be used selectively by nutrition experts in order to orient food selection toward a healthy diet composition.
Excitatory Amino Acid Neurotransmission in the Primary Gustatory Nucleus of the GoldfishCarassius auratus
Authors: SMERASKI CYNTHIA A. , DUNWIDDIE THOMAS V. , DIAO LIHONG , FINGER THOMAS E.
Published: February 2006

ABSTRACT:The vagal lobe in goldfish is a laminated structure in the midmedulla responsible for processing vagal gustatory input from the oropharynx. The anatomical arrangement of the vagal lobe is conducive to anin vitroslice preparation for investigating the physiology and pharmacology of primary gustatory fibers. Postsynaptic population responses (N2 and N3) were evoked from sensory layers of the vagal lobe following stimulation of the incoming vagal fibers. Application of 100 μM kynurenic acid, a broad spectrum glutamate receptor antagonist, abolished or significantly decreased the evoked responses. These results indicate that excitatory amino acids are the neurotransmitter at the first relay in the taste pathway in the central nervous system.
Differential Distribution of Amygdaloid Input across Rostral Solitary Nucleus Subdivisions in Rata
Authors: Halsell Christopher B.
Published: February 2006

ABSTRACT: The orosensory nucleus of the solitary tract (NST) receives input from the amygdala, a key node in the forebrain feeding‐related network. Despite numerous studies documenting the existence of this pathway, however, too little is known about the input organization to the gustatory brainstem to allow definitive conclusions about its functional role. Therefore, towards the long‐term goal of characterizing such descending regulatory pathways, the purpose of the present study was to describe the distribution of input arising from the amygdala. The anterograde tracer, biotinylated dextran, was injected into the central amygdala based on stereotaxic coordinates in seven adult male rats. Following a 2‐week survival time, the animals were sacrificed. Transverse sections of the brains were processed to visualize transported tracer and NST anatomical topography. Labeled fibers were differentially distributed among subdivisions throughout the rostrocaudal extent of NST. Within the rostral NST, the medial (M) subdivision had the highest density of terminal‐like endings and swellings (30% of total density), followed by the ventral half of rostral central (vRC, 29%), ventral (V, 25%), dorsal half of rostral central (dRC, 12%) and rostral lateral (RL, 4%). In conclusion, it appears that amygdalar input preferentially overlaps with NST subdivisions (M, V, vRC) containing neurons with local efferent projections to the caudal NST and reticular nuclei that are implicated in medullary reflex circuits, rather than with subdivisions (dRC, RL) receiving primary orosensory afferent input and containing neurons having ascending efferent projections to the parabrachial nucleus. Thus, descending feeding‐related pathways may be positioned to act as regulatory substrates controlling the output gain of brainstem circuits which may serve to modulate sensorimotor and autonomic reflexes in response to ingestive behaviors.
Temporal Process from Receptors to Higher Brain in Taste Detection Studied by Gustatory‐Evoked Magnetic Fields and Reaction Times
Authors: Saito Sachiko , Endo Hiroshi , Kobayakawa Tatsu , Ayabe‐Kanamura Saho , Kikuchi Yoshiaki , Takeda Tsunehiro , Ogawa Hisashi
Published: February 2006

ABSTRACT: Using magnetoencephalography (MEG) and a taste stimulator with rapid‐rise time, we previously located the primary gustatory area in the human cerebral cortex and also investigated the relation between the onset latency of the gustatory‐evoked magnetic fields (GEM) and reaction times (RT) in different taste qualities. In the present study, we investigated the temporal process from receptors to the higher brain in taste detection based on the results of the GEM and RT of different tastes. We used 100 mM, 300 mM and 1 M NaCl and 3 mM saccharine. The duration of each stimulus was 400 ms. The interstimulus interval was ∼30 s. The temperature of both taste solution and deionized water was maintained the same as that of the tongue. Four subjects participated in this experiment. The 64‐channel whole‐head SQUID system (CTF Systems Inc., Canada) was used to measure GEM. The sampling rate was 250 Hz, and the low‐pass filter was 40 Hz. In each subject, GEM and RT to a given taste were measured separately by applying 40 trials of stimulation. After each trial of both measurements, subjects showed a perceived intensity by using their fingers. In the GEM study, the trials contaminated with eye movements were rejected and the remaining trials were averaged. Averaged GEM were superimposed on the same sheet with all 64 channels to measure the onset latecy of GEM from the stimulus onset. RT and onset latencies of GEM were longer for saccharine than NaCl, and the value of RT minus the onset latency of GEM from RT, presumably indicating the time for higher brain process plus motor process, did not differ between 3 mM saccharine and 1 M NaCl. With increased concentrations of NaCl, RT became shorter, but onset latencies of GEM remained constant. Sweet taste took a longer time than salty taste at receptor process including the time for diffusion to receptors.
An Improved Model of the Synaptic Organization of Insect Olfactory Glomeruli
Authors: DISTLER PAUL G. , BOECKH JüRGEN
Published: February 2006

ABSTRACT: In order to characterize the neuronal pathways underlying central nervous processing of odor signals, the synaptic circuitry of identified neuron individuals or types within cockroach antennal lobe glomeruli has been studied in the electron microscope. The anatomical findings are consistent with physiological data from other investigations. For the characterization of the synaptic connections, different combinations of neuron labelings have been applied including (a) horseradish peroxidase injection of local interneurons (INs) or uniglomerular projection neurons (uPNs), (b) γ‐aminobutyric acid (GABA)‐immunogold labeling, and (c) experimentally induced degeneration of antennal receptor neuron projections (RNs). The following pathways between glomerular input and output neurons are proposed: (1) A monosynaptic excitatory route, and (2) at least two polysynaptic routes, one of them probably inhibitory and the other disinhibitory. (3) Inhibitory feedback connections exist from these two paths via GABA‐positive INs onto both, RNs as well as uPNs. (4) Since a given GABA‐positive IN innervates a large number of antennal lobe glomeruli, inhibitory signals could also be passed to neighbored glomeruli.
Behavioral Antagonism in the Moth Helicoverpa zea in Response to Pheromone Blends of Three Sympatric Heliothine Moth Species Is Explained by One Type of Antennal Neurona
Authors: BAKER THOMAS C. , COSSÉ ALLARD A. , TODD JULIE L.
Published: February 2006

ABSTRACT: We have discovered a type of sensillum on the antennae of male corn earworm moths, Helicoverpa zea, that houses two types of receptor neuron (RN) that explains both the upwind flight attraction of males to their own species' Pheromone blend and arrestment to the quite similar blends emitted by females of three other sympatric North American heliothine species. The first RN type is a large‐spiking neuron that is most sensitive to (Z)‐9‐hexadecenal (Z9‐16:Ald), the secondary H. zea Pheromone component that along with the major component, (Z)‐11‐hexadecenal, causes attraction to the female. This RN is also responsive to (Z)‐9‐tetradecenal (Z9‐14:Ald; not a H. zea Pheromone component) at higher dosages. The sensitivity of this RN thus explains the attraction that has been observed in other studies when small proportions of Z9‐14:Ald are added to Z11‐16:Ald to mimic the conspecific blend. The second type of RN in this sensillum is a small‐spiking neuron that is again responsive to Z9‐14:Ald (which in larger proportions acts as a strong antagonist to upwind flight), but this RN is actually more sensitive to two other strong behavioral antagonists, (Z)‐11‐hexadecenyl acetate and (Z)‐11‐hexadecenol. Thus, activation of this single broadly tuned 'antagonist' RN could explain why H. zea males will orient only to their conspecific females. These three compounds are emitted by females of three other North American species, H. subflexa, H. phloxiphaga, and H. virescens, as agonists in their blends, which also contain the H. zea components Z11‐16:Ald and Z9‐16:Ald. This antagonist RN may also explain why a blend of Z11‐16:Ald and a small amount of Z9‐14:Ald is never as attractive to H. zea males as the conspecific blend. Enhanced specificity for the conspecific blend arises because the antagonist RN is never stimulated to fire, even when large proportions of the Pheromone component, Z9‐16:Ald, are added to Z11‐16:Ald. When Z9‐14:Ald is used instead of Z9‐16:Ald, however, and the proportion of Z9‐14:Ald becomes too great, the threshold of the antagonist neuron as well as that of the agonist neuron is exceeded, and the upwind flight response begins to be suppressed.
A Combinatorial Model of Odor Discrimination Using a Small Array of Contiguous, Chemically Defined Glomeruli
Authors: VICKERS NEIL J. , CHRISTENSEN THOMAS A.
Published: February 2006

ABSTRACT: The macroglomerular complex (MGC) is a sexually dimorphic array of contiguous glomeruli in male moths, located at the base of the antennal nerve where it enters the primary olfactory processing area of the brain, the antennal lobe. A new three‐dimensional reconstruction method was used to map this glomerular array, and images obtained with the laser scanning confocal microscope revealed the precise location and spatial arrangement of the MGC glomeruli in two related species of Heliothine moth. Intracellular recording and staining of projection neurons (PNs) that arborize within the MGC has revealed that information about the two attractive components of the Pheromone blend is segregated to different glomeruli in both species. In one species, Helicoverpa zea, a third glomerulus serves as the locus for the processing of odors that antagonize upwind flight. Thus, activation of different but overlapping sets of glomeruli within the MGC may provide a neural substrate for discriminating attractant vs antagonist chemical signals.
Tyrosine Phosphorylation Downregulates a Potassium Current in Rat Olfactory Bulb Neurons and a Cloned Kv1.3 Channela
Authors: FADOOL DEBRA ANN
Published: February 2006

ABSTRACT: We are studying the regulation of ion channels by protein tyrosine kinases (TKs) using olfactory bulb neurons (OBNs) and a cloned voltage‐dependent potassium channel, Kv1.3, as models. Rat OBNs, which express Kv1.3 channels, had whole‐cell outward currents that were suppressed by picomolar quantities of margatoxin and showed a slow inactivation that increased over a 10‐min period. These same pharmacological and kinetic properties were found also in human embryonic kidney (HEK 293) cells transfected with rat Kv1.3 cDNA. The insulin receptor TK was detected in the OB by Western analysis. Exogenous application of insulin was found to suppress whole‐cell outward current in all OBNs tested. Perfusion of the nonreceptor Src kinase likewise suppressed outward current. Current was not suppressed with heat‐inactivated Src or when adenosine triphosphate (ATP) was excluded from the pipette solution. The membrane permeant tyrosine phosphatase inhibitor, pervanadate, was found to suppress current in a subset of neurons, implying the presence of an endogenous tyrosine kinase in these neurons. Using site‐directed mutagenesis of six tyrosine residues contained within good recognition motifs for tyrosine phosphorylation, we constructed conservative Y to F mutations in the Kv1.3 cDNA and expressed the Kv1.3 channels in HEK 293 cells. We found that Tyr449 is a target for both the pervanadate‐ and Src‐induced suppression of Kv1.3 current; Tyr111, 112 and 113 are also important for modulation by pervanadate; and Tyr137 is a target for modulation by Src. In summary, tyrosine phosphorylation of Kv1.3 and related channels may be involved in the modulation of OBN excitability.
fMRI Study of Taste Cortical Areas in Humans
Authors: Faurion Annick , Cerf Barbara , Le Bihan Denis , Pilliasa Anne‐Marie
Published: February 2006

ABSTRACT: We used 3 Tesla functional magnetic resonance imaging (fMRI) with echo planar imaging to map taste projections in the human. Activations were found surrounding and buried in the sylvian fissure; the upper part of insula, the frontal operculum, and the foot of the pre‐ and postcentral gyri were usually activated. Moreover, we could describe, for the first time, a lateralized associative projection located in the lower part of the dominant hemisphere of the subject (n= 10). We also observed activations in the anterior cingulate gyrus, the centromedial thalamus, and other areas related to emotional or cognitive processes.

Thirty subjects were submitted to a familiarization experiment sampling neophobic and nonneophobic stimuli. Measurements of isointense concentrations, magnitude estimates and hedonic values were assessed repetitively for 10 weeks. Five subjects performed 3 fMRI experiments, before, during and after familiarization.

Psychophysical data showed a relationship between the evolution of the hedonic assessment and the intensity of the perception, and fMRI results showed a relationship between the evolution of the hedonic assessment and the evolution of the percent of activated pixels in taste cortical area.