bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurotrophic Factors in the Tongue: Expression Patterns, Biological Activity, Relation to Innervation and Studies of Neurotrophin Knockout Micea
Authors: NOSRAT CHRISTOPHER A.
Published: February 2006

ABSTRACT: How taste buds develop and how they become innervated has been a matter of debate for a long time. Brain‐derived neurotropic factor (BDNF) and neurotrophin‐3 (NT3) mRNA expression patterns suggested a possible involvement in lingual gustatory and somatosensory innervation. Studies of null‐mutated mice showed that BDNF−/− mice had few abnormal taste buds and were unable to discriminate between primary tastes. NT3−/− mice had a severe loss of lingual somatosensory innervation. These novel findings may have clinical implications in rare human conditions such as familial dysautonomia and/or in more common cases of problems with loss of taste and sensation in the mouth such as those seen after injury to the nerves, either by accident or following oral/facial surgery. Knowledge about which proteins that are required to stimulate nerve fibers to grow into mucous membranes of the oral cavity during development suggests that these same proteins might become helpful in stimulating regeneration of injured nerves in patients, perhaps helping them to regain lost taste and sensory functions.

Here, the presence of glial cell‐derived neurotrophic factor (GDNF) families of neurotrophic factors and receptors in the tongue is also discussed. Further, a model for the development and innervation of taste buds in mammals is proposed.
The Role of Innervation in the Development of Taste Buds: Insights from Studies of Amphibian Embryosa
Authors: BARLOW LINDA A. , NORTHCUTT R. GLENN
Published: February 2006

ABSTRACT: Amphibian embryos have long been model organisms for studies of development because of their hardiness and large size, as well as the ease with which they can be experimentally manipulated. These particular advantages have allowed us recently to test the role of innervation in the development of vertebrate taste buds using embryos of an aquatic salamander, the axolotl. The predominant model of taste bud genesis has been one of neural induction, in which ingrowing sensory neurites induce taste bud differentiation in the epithelium that lines the mouth and pharynx. However, when we prevented embryonic sensory neurons from contacting the oropharyngeal epithelium by using transplantation or tissue culture techniques, we found that taste bud differentiation was independent of nerve contact. Additionally, using similar types of experimental manipulations, we have recently shown that taste bud differentiation is not a result of interactions of the oropharyngeal epithelium with craniofacial mesenchyme. Surprisingly, we found that although taste bud genesis occurs very late in embryonic development, it is an intrinsic feature of the presumptive oropharyngeal epithelium extremely early, in fact as early as the completion of gastrulation. These data have prompted us to propose a new model for the development of amphibian taste buds: (i) The presumptive oropharyngeal epithelium is specified by the time gastrulation is complete; (ii) Subsequently, a distributed population of taste bud progenitors is set up within this epithelium via local cell‐cell interactions. These progenitor cells give rise to taste buds, which are distributed throughout the mouth and pharynx. How widely applicable this model might be for the genesis of taste buds in other vertebrates remains to be seen. However, since it is likely that the taste system of axolotls more closely resembles the ancestral state from which both the amphibian and mammalian taste systems have evolved, it is possible that many of the same developmental mechanisms that give rise to amphibian taste buds are also used to generate these receptor organs in mammals.
Quantitative Relationships between Taste Bud Development and Gustatory Ganglion Cellsa
Authors: KRIMM ROBIN F. , HILL DAVID L.
Published: February 2006

ABSTRACT: To determine whether patterns of taste bud innervation change during postnatal rat development, the number of geniculate ganglion cells that innervate single taste buds were quantified in adult and developing rats. While there was a large variation in numbers of ganglion cells that innervate individual taste buds, there was a high degree of organization in the system. Namely, the number of labeled geniculate ganglion cells innervating a taste bud was highly correlated with the size of the taste bud. This relationship between taste bud size and number of innervating ganglion cells develops over a prolonged postnatal period and is not established until postnatal day 40 (P40), when taste buds reach their adult size.

In a second series of experiments, we sought to determine whether neural rearrangement of chorda tympani neurons is responsible for the development of this relationship by double‐labeling single taste buds at different ages. We found that the number of ganglion cells innervating individual taste buds on P10 predicts the size that taste buds become by P40. This finding suggests that neural rearrangement is not responsible for establishing the relationship between taste bud size and the number of innervating ganglion cells during development. More importantly, it strongly suggests that the 'neural template' for the mature innervation pattern is determined during early postnatal development.
Central Olfactory Structures in Pax‐6 Mutant Micea
Authors: LOPEZ‐MASCARAQUE LAURA , GARCÍA CONCEPCIÓN , VALVERDE FACUNDO , DE CARLOS JUAN A.
Published: February 2006

ABSTRACT: During the development of the olfactory system, cells located in the olfactory placode/olfactory pit send their axons toward the rostral part of the telencephalic vesicles (TVs). Some of these enter the TV inducing the formation of the olfactory bulbs (OBs), whereas, mitral and tufted cell axons form the lateral olfactory tract (LOT). Our recent studies have shown that the beginning of the central olfactory projections is independent of the arrival of olfactory receptor neuron (ORN) axons to the TV. Here we have used the mouse carrying a mutation in the Pax‐6 gene to study whether the nasal olfactory structures intervene in the formation of central olfactory structures. This mutant as well as lacking a nose and eyes, is reported to lack olfactory epithelium and OB. However, we have found an ovoid cellular structure localized in the rostral part of the brain, and some cells in this structure project axons toward the piriform cortex forming a presumptive LOT. We conclude that the referred structure is an OB, which fails to develop because the mutation in the Pax‐6 gene affects the formation of nasal structures. As such, fibers of the ORNs are necessary for the protrusion and layered formation of the OB, but these inputs are not necessary for the establishment of the central olfactory projections.
Compensatory Responses to Early Olfactory Restrictiona
Authors: LEON MICHAEL
Published: February 2006

The emphasis on the effects of early olfactory restriction has been on the deleterious nature of the consequences of this abnormal early experience. While these effects are certainly present and dramatic, it is also the case that the olfactory system is left fairly intact by this experimental manipulation. If one asks what mechanisms may account for the preservation of the developing olfactory system in the face of diminished activity, there are a number of neural response that could help the system compensate for the damage inflicted upon the system by the loss of early sensory stimulation. I describe what may be compensatory responses to the decrease in dopamine, the increase in norepinephrine, the structural changes induced in the glomeruli and the increase in cell death within the olfactory bulb that follow neonatal unilateral naris occlusion.
The Arginine Taste Receptor: Physiology, Biochemistry, and Immunohistochemistrya
Authors: GROSVENOR WILLIAM , FEIGIN ALEXANDER M. , SPIELMAN ANDREW I. , FINGER THOMAS E. , WOOD MALCOLM R. , HANSEN ANNE , KALINOSKI D. LYNN , TEETER JOHN H. , BRAND JOSEPH G.
Published: February 2006

ABSTRACT: The amino acid, l‐arginine (L‐Arg), is a potent taste stimulus for the channel catfish, Ictalurus punctatus. Receptor binding studies demonstrated a high‐affinity binding of L‐Arg to putative taste receptor sites. This binding could be inhibited by preincubation of the tissue in the lectins Phaseolus vulgaris agglutinin (PHA) and Ricinus communis agglutinin I (RCA I). Neurophysiological studies demonstrated that the L‐Arg receptor is a stimulus‐gated ion channel type receptor whose conductance was stimulated by L‐Arg and inhibited by d‐arginine (D‐Arg). To purify the receptor we subjected CHAPS solubilized partial membrane preparation from barbel epithelium to RCA I lectin affinity chromatography. The bound proteins were eluted with d‐galactose. When these proteins were reconstituted into lipid bilayers, L‐Arg activated single channel currents with conductances between 45 and 85 pS. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS‐PAGE) of the eluted protein showed a distinct band at ∼ 83 kDa. Polyclonal antibodies raised against this 83‐kDa band in guinea pigs reacted with numerous small (∼ 1μm) sites within the taste pore of every taste bud when applied to fixed nonpermeabilized barbels. This observation suggests that the antibodies recognize an externally‐facing epitope of the putative Arg receptor. The antibodies also inhibited L‐Arg‐stimulated currents in reconstitution studies. Sephacryl S‐300 HR chromatography of the eluant from the affinity column showed a high molecular weight peak (>700 kDa) which was recognized by the antibodies. Reconstitution of the protein from this peak into a lipid bilayer resulted in L‐Arg‐stimulated channels that could be inhibited by D‐Arg. This high molecular weight component may be aggregates of the arginine taste receptor.
Taste Preference in Nonhuman Primates to Compounds Sweet in Mana
Authors: GLASER DIETER , TINTI JEAN‐MARIE , NOFRE CLAUDE
Published: February 2006

ABSTRACT: Primates have stimulated more interest than any other group as humans are ranked in this same mammalian order. Gustatory responses of human and nonhuman primates have already been compared for compounds such as monosaccharides, oligosaccharides, polyols, amino acids, dipeptides, proteins, dihydrochalcones, sulfamates, saccharin, acesulfame, diterpenes or urea derivatives, all known to be sweet in man. But no rational comparison in primates has been attempted. Using a structure‐activity relationship study in primates, it is now possible to classify the primate sweetness receptors into four types according to the behavioral responses observed from various selected compounds sweet in humans. The four types are represented by (1) the Callitrichidae and (2) the Cebidae, both from the infraorder Platyrrhini (New World monkeys), (3) the Lemuridae and Lorisidae, from the suborder Prosimii (prosimians), and (4) the Cercopithecidae (Old World monkeys), Hylobatidae (lesser apes), Pongidae (great apes), and Hominidae (humans) from the infraorder Catarrhini (Old World simians). By a comparative study of the putative receptor recognition sites postulated for each type of receptor, it is inferred that the Callitrichidae (marmosets and tamarins) have retained the most primitive sweetness receptor among primates. As we believe that the evolution of the sweetness receptor is a key factor involved in the raising of nonhuman primates from a ‘primitive grade’ towards a more ‘advanced’ or ‘simian grade,’ the possible phylogenetic implications of these findings will be discussed.
Genome Dynamics, Evolution, and Protein Modeling in the Olfactory Receptor Gene Superfamilya
Authors: SHARON DROR , GLUSMAN GUSTAVO , PILPEL YITZHAK , HORN‐SABARN SHIRLEY , LANCET DORON
Published: February 2006

ABSTRACT: The human olfactory subgenome represents several hundred olfactory receptor (OR) genes in a dozen or more clusters on several chromosomes. One OR gene cluster on human chromosome 17 has been characterized by us in detail. Based on a large‐scale DNA sequence analysis, we have identified events of gene duplication and fusion as well as the generation of pseudogenes. The latter instances of 'gene death' could underlie the widespread phenomenon of human specific anosmias. Sixteen OR coding regions were found on this cluster, and six of them are pseudogenes. One of these pseudogenes, OR17‐23, was found to be an intact open reading frame in an old world monkey. This may be a reflection of an OR repertoire diminution in man. A homology model of the OR protein was constructed by utilizing the rich information available on ~ 200 OR sequences. The putative odorant complementarity determining regions (CDR) was found to consist of 20 hypervariable residues facing an interior caving defined by transmembrane helices 3, 4 and 5. Such a model could be useful in analyzing additional OR gene sequences in the human genome in terms of odorant binding.
Generation of Neurons from a Nonneuronal Precursor in Adult Olfactory Epithelium in Vitro
Authors: Sicard G. , Féron F. , Andrieu J. L. , Holley A. , Mackaysim A.
Published: February 2006

ABSTRACT: Within the olfactory epithelium is a stem cell which can divide and differentiate to produce new sensory neurons. The identity of the neuronal stem cell is unknown but one candidate is the horizontal basal cell which lies adjacent to the basement membrane and expresses keratin. Previous attempts to generate mature sensory neurons from purified horizontal basal cells in vitro were unsuccessful. We show here for the first time that olfactory neurogenesis can be reproduced in vitro from partially‐purified cultures of adult rat precursor cells cultivated in a serum‐free medium. Rat olfactory epithelium was dissected from the nasal septum and separated from the underlying lamina propria, and its cells were dissociated and grown in a medium containing epidermal growth factor for 5 days. Immunochemistry showed that only supporting cells (SUS1‐positive) and horizontal basal cells (keratin‐positive) survived for this period. At day 6, the cells were stressed either by passaging them or by a simple mechanical stress. In each case, a morphological and immunological differentiation was observed within 24‐48 hr. Newly formed bipolar cells were found to be S100−, glial fibrillary acidic protein (GFAP−), neural cell adhesion molecule (N‐CAM+), and/or microtubule‐associated protein 5 (MAP‐5+). After passaging 14% of the surviving cells were immature neurons (MAP‐5+) and 4% were mature olfactory neurons (MAP‐5+) and olfactory marker protein (OMP+)). In addition the same experiment was conducted on transgenic mice in which the lacZ gene was linked to the OMP promoter. Using 5‐bromo‐4‐chloro‐3‐indolyl‐β‐D‐galactopyranoside (X‐Gal) staining we showed that OMP+ cells disappeared before day 5 in culture but reappeared after passaging. These results suggest that olfactory sensory neurons can arise from a nonneuronal precursor, probably the keratin‐positive horizontal basal cell.
Differentiation in an Olfactory Cell Line: Analysis via Differential Displaya
Authors: ZEHNTNER SIMONE P. , MACKAY‐SIM ALAN , BUSHELL GILLIAN R.
Published: February 2006

ABSTRACT: The olfactory epithelium is a unique system, in which new neurons are continually generated throughout adult life. Olfactory neurons are derived from stem cells that lie adjacent to the basal lamina of the olfactory epithelium; these stem cells divide several times and their progeny differentiate into mature sensory neurons. In our laboratory immortalized cell lines have been derived from these dividing cells. The morphology of these cell lines and their expression of neuronal markers varies with culture conditions. When grown in low serum medium one of these cells lines, OLF 442, differentiates by extending long neurites and increasing its expression of neurofilament and B50/GAP43 proteins at the same time reducing expression of glial fibrillary acidic protein (GFAP).

Identification of differentially expressed mRNA in cell lines has previously relied on both screening for known markers, and the use of subtractive techniques for identification of unique mRNA species. The differential display technique allows simultaneous detection of differentially expressed mRNA at different time periods and growth conditions. A modified Liang and Pardee differential display technique was used to screen OLF 442 over a number of time intervals in serum‐depleted media, and compared with OLF 442 grown in complete media. The differentially displayed fragments were cloned and sequenced, leading to the identification of a number of sequences, both known and unknown. The known sequences include SPARC (encoding a Ca2+ binding secreted Protein which is Acidic and Rich in Cysteine), which is reported to function as a modulator of the cell matrix, and RHAMM, the receptor for hyaluronan‐mediated motility. Both the known and the unknown sequences are being studied further to provide insight into the differentiation of olfactory neurons.
Influence of Olfactory Innervation on Neurogenesis in the Developing Olfactory Bulb of the Frog, Xenopus laevisa
Authors: BURD GAIL D. , SEIN VICTOR
Published: February 2006

ABSTRACT: Previous research on development of the Xenopus olfactory bulb from our laboratory has shown that mitral cells begin to differentiate after olfactory axons make contact with the olfactory bulb, and the number of olfactory axons is correlated with the number of mitral cells throughout development. In embryos, removal of all afferent innervation before the mitral cells begin to differentiate results in a failure of the bulb to form; removal of half the olfactory axons, results in development of half the normal number of mitral cells. At larval stages, transection of the olfactory nerve results in a decrease in the number of neurons in the olfactory bulb. Thus, the olfactory axons play a major role in stimulating or maintaining development of the olfactory bulb neurons. Since we have found that neurogenesis in the bulb continues through metamorphosis, the goal of the current study was to determine whether olfactory axons influence cell genesis and/or neuronal maturation in the larval olfactory bulb. To study cell genesis, we cut the olfactory nerves, and 6 days later, injected the animals with [3H]thymidine. After 6 hr, the animals were killed and the tissue was processed for autoradiography. The number of labeled cells in the ventricular zone of the olfactory bulb was determined in every fifth section through the bulb in control and experimental animals. There was no statistical difference (Mann‐Whitney rank sum test) in the number of labeled ventricular cells between controls and experimentals. Thus, olfactory axon innervation does not appear to play a role in precursor cell division during larval development. To study the influence of olfactory axon innervation on the ability of newly generated neurons to mature, we followed the same procedures. However, the animals were killed 21 days after the [3H]thymidine injection. The results from this experiment showed that there are many fewer labeled mitral cells in the experimental animals at 21 days. Together these results suggest that sensory deafferentation influences mitral cell differentiation or survival even during late stages of larval development.
Neurogenesis in the Central Olfactory Pathway of Adult Decapod Crustaceansa
Authors: SCHMIDT MANFRED , DEMUTH STEFAN
Published: February 2006

ABSTRACT: Based on the previous findings that the number of olfactory projection neurons increases continuously in adult shore crabs, Carcinus maenas, and that this increase is associated with the presence of 5‐bromo‐2′‐deoxyuridine (BrdU)‐positive, proliferating cells in the appropriate soma clusters (lateral soma clusters),1 we studied the further fate of these proliferating cells and the presence of apparent adult neurogenesis throughout the central olfactory pathway of diverse species of decapod crustaceans. Double labeling experiments combining biocytin‐backfills and in vivo BrdU labeling as well as BrdU labelings with extended survival times (1 month) indicate that the cells proliferating in the lateral soma clusters of adult Carcinus undergo neuronal differentiation in about 3‐4 weeks. In vivo BrdU labeling of different species representing important taxa of decapod crustaceans (shrimps, spiny lobsters, clawed lobsters, crayfish) revealed that neurogenesis among olfactory projection neurons is a constitutive feature of the adult decapod brain. In contrast, adult neurogenesis of the other neuron types present in the central olfactory pathway occurs in a taxon‐specific manner and appears to be related to the development and reduction of accessory lobes throughout decapod phylogeny.
Inhibitors of Sensillar Esterase Block Reversibly the Responses of Moth Pheromone Receptor Cells
Authors: POPHOF B.
Published: February 2006

ABSTRACT: The Pheromone of Antheraea polyphemus is slowly (within min) degraded by a sensillum lymph specific esterase. The effects of two volatile alkyl‐thio‐trifluoro‐methyl‐ketones with alkyl chain length of six (HTFP) and ten carbons (DTFP), which selectively inhibit the activity of the sensillar esterase, were tested.

Single sensillum recordings from sensilla trichodea were performed on isolated antennae either held in a continuous stream of clean air, or exposed to an airstream containing one of the esterase inhibitors. Afterwards the antennae were stimulated with the Pheromone components (E,Z)‐6,11‐hexadecadienyl acetate and (E,Z)‐6,11‐hexadecadienal. Both esterase inhibitors caused a reduction of electrophysiological responses to each of the two Pheromone compounds. The DTFP was slightly more effective then HTFP. An almost complete block of the receptor potential amplitude and nerve impulse response was achieved within seconds of exposure to the inhibitors. Responses of both Pheromone receptor cells were reduced to the same extent. The half‐times of rise and decline of the receptor potential remained unaffected in most cells. The responses to Pheromone partially recovered to ~50‐70% within several min in clean air.

An inhibition of the sensillar esterase cannot explain the observed effects. The inhibitors could either react directly with the receptor molecules, thereby inhibiting the action of the Pheromone, or bind to the Pheromone‐binding protein (PBP) and prevent the formation of the Pheromone‐PBP complex stimulating the receptor.
Vomeronasal, Olfactory, Hormonal Convergence in the Brain: Cooperation or Coincidence?a
Authors: MEREDITH MICHAEL
Published: February 2006

ABSTRACT: This paper briefly reviews three topics: (a) Convergent vomeronasal and olfactory chemosensory input into a common circuit considered important for mating in male golden hamsters; (b) Apparent activation of this circuit by intracerebral luteinizing hormone‐releasing hormone (LHRH) and (c) Interaction of the LHRH and the two chemosensory inputs. Mapping of c‐fos protein in male hamsters mating with females or exposed to female Pheromones indicates intense activation in the central vomeronasal pathways, induced by both olfactory and vomeronasal input. This input appears to activate the medial preoptic area, where chemosensory activation is greater in experienced than in inexperienced animals. Intracerebral injection of LHRH facilitates mating behavior and increases Fos expression in the medial preoptic area of mating males. Despite evidence that the release of LHRH in response to female chemosignals is dependent on vomeronasal input, no activation of LHRH neurons has been demonstrated in males exposed to such chemosignals. Electrical stimulation of the vomeronasal organ can induce Fos expression in chemosensory pathways and in medial preoptic LHRH neurons.
The Human Vomeronasal System: A Review
Authors: MONTI‐BLOCH LOUIS , JENNINGS‐WHITE CLIVE , BERLINER DAVID L.
Published: February 2006

ABSTRACT: Recent publications show that the human vomeronasal organ (VNO) develops and grows during gestation, and is present in all adult humans. The human VNO has a unique ultrastructure, with elongated bipolar microvillar cells that stain with several immunomarkers. These cells show physiological properties similar to chemosensory receptor cells of other mammalian species. The adult human VNO displays species‐specific, gender‐dimorphic and highly stereospecific responses to ligands. The organ's local response, or electrovomerogram, is followed by gender‐specific behavioral changes, modulation of autonomic nervous system function, or the release of gonadotropins from the pituitary gland. Functional brain imaging studies revealed consistent activation of the hypothalamus, amygdala and cingulate gyrus‐related structures during adult human VNO stimulation. These findings present new information supportive of a functional vomeronasal system in adult humans.
Development and Genetics of Glutamate Taste Preferencea
Authors: BEAUCHAMP GARY K. , BACHMANOV ALEXANDER , STEIN LESLIE J.
Published: February 2006

ABSTRACT: The sodium salt of glutamic acid, monosodium glutamate (MSG), and certain other amino acids and ribonucleotides impart a unique taste sensation often called 'umami.' We have been studying preference for umami substances in two systems: inbred mice and human infants. In 48‐hr tests, C57BL/6J (C57) mice exhibit a lower preference threshold for MSG than do 129/J mice. Moreover, C57 mice show a greater preference across a wide range of concentrations and, at high (e.g., 300‐600 mM) concentrations, consume greater amounts of MSG. To examine whether the strain difference in MSG preference might be related to a similar strain difference in preference for sucrose and other sweeteners, as might be suggested from studies with rats, preferences for MSG and sucrose in the second (F2) generation were examined. Preferences for sucrose and for MSG were not positively correlated in the F2 indicating that these strain differences depend on different genes. For human adults, unlike mice, the taste of aqueous MSG is not palatable. Our studies of human infants also indicate that MSG alone is not preferred to plain water, but, when it is added to soup, the soup plus MSG is preferred to soup alone. Ongoing studies are designed to determine whether simple mixtures of MSG with other tastants, in particular NaCl, are preferred to water alone, NaCl alone, and MSG alone.
Hypothalamic Control of Amino Acid Appetitea
Authors: Torii K. , Kondoh T. , Mori M. , Onoc T.
Published: February 2006

ABSTRACT: Preference for umami taste materials, such as monosodium l‐glutamate (MSG) and the 5'‐ribonucleotides, inosine 5'‐monophosphate (IMP) and guanosine 5'‐monophosphate (GMP), varies as a consequence of protein nutrition. Rats fed diets deficient in dietary protein or an essential l‐amino acid (AA), l‐lysine (Lys), avidly consumed Lys, glycine and NaCl but not umami substances. However, when the rats' protein nutrition was normal or when they were recovering from deficiency, a preference for umami substances was evident. These data suggest that the central mechanism for recognition of protein malnutrition may be coupled with umami taste preference. To test this, Lys‐deficient and normal rats were employed as a model for taste preference changes. AA levels in plasma and brain remain essentially unchanged throughout the day while the rat is on standard chow but are altered during Lys deficiency. The recognition site for the deficit in the rats' brains was localized to the ventromedial (VMH) and lateral (LHA) hypothalamus as determined by functional magnetic resonance imaging (fMRI, 4.7 Telsa). Studies of single neuron activity in the LHA of Lys‐deficient rats suggested that neuronal plasticity occurred. Following Lys deficiency, cells responded specifically to Lys, both iontophoretically applied and during ingestion of AA. Other LHA neurons of nondeficient rats differentially responded to MSG. The present results suggest that the LHA and probably the VMH play important roles in recognition of deficient nutrients. Neural plasticity of hypothalamic cells helps maintain AA homeostasis. Furthermore, a preference for umami substances may be an indicator that the organism (rat or human) is free of protein malnutrition.
Excitatory and Inhibitory Modulation of Taste Responses in the Hamster Brainstema
Authors: SMITH DAVID V. , LI CHENG‐SHU , DAVIS BARRY J.
Published: February 2006

ABSTRACT:The rostral portion of the nucleus of the solitary tract (NST) contains second‐order gustatory neurons, sends projections to the parabrachial complex and brainstem reticular formation, and receives descending projections from several nuclei of the ascending gustatory pathway. Electrophysiological responses of NST neurons can be modulated by several factors, including blood glucose and insulin levels and taste aversion conditioning. We are using extracellular electrophysiological recordingin vivo,combined with local microinjection of neurotransmitter agonists and antagonists, to study the mechanisms by which taste responses of cells in the hamster NST can be modulated. Afferent fibers of the chorda tympani (CT) nerve make excitatory synaptic contact with NST neurons; this excitation is probably mediated by the excitatory amino acid glutamate. Microinjection of kynurenic acid, a nonspecific glutamate receptor antagonist, into the NST completely and reversibly blocks afferent input from the CT nerve, produced by either anodal electrical or chemical stimulation of the anterior tongue. The non‐NMDA ((RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate) receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX) also completely blocks gustatory input to these cells, whereas theN‐methyl‐d‐aspartate (NMDA) antagonist dl‐2‐amino‐5‐phosphonovalerate (APV) produces only a small effect. There are many γ‐aminobutyric acid (GABA)‐containing neurons within the NST and taste‐responsive NST cells are maintained under a tonic GABAergic inhibition. Microinjection of the GABAAreceptor antagonist bicuculline methiodide increases the taste responsiveness of NST neurons, whereas application of GABA inhibits taste responses in these cells. Preliminary data show that GABAergic inhibition can be produced by stimulation of the gustatory cortex. There are both intrinsic substance P (SP)‐containing neurons and extrinsic SP‐immunoreactive fibers in the rostral NST. Microinjection of SP into the NST enhances the responses of many NST cells to gustatory stimulation; NaCl‐best neurons are preferentially excited by SP.
Glutamate and Synaptic Plasticity at Mammalian Primary Olfactory Synapsesa
Authors: ENNIS MATTHEW , LINSTER CHRISTIANE , ARONIADOU‐ANDERJASKA VASSILIKI , CIOMBOR KELLY , SHIPLEY MICHAEL T.
Published: February 2006

ABSTRACT: Glutamate is the transmitter at synapses from the olfactory nerve (ON) to mitral (Mi)/tufted cells, but very little is known about the functional properties of this synapse. This report summarizes in vitro physiological and computational modeling studies investigating glutamatergic neurotransmission at ON → Mi cell synapses. Single ON shocks in rat main olfactory bulb (MOB) slices elicit distinct early and late spiking components triggered, respectively, by (RS)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainic acid (KA) and N‐methyl‐d‐aspartate (NMDA) receptor activation. Modeling simulations showed that the placement of both AMPA/KA and NMDA receptors on Mi apical dendrites replicates the experimentally observed early and late Mi spiking responses to ON shocks. Brief, tetanic ON stimulation in vitro induced robust, selective long‐term potentiation (LTP) of NMDA receptor‐dependent spiking. Modeling experiments disclosed several potential mechanisms underlying the selective LTP of NMDA receptor‐dependent spiking. These findings demonstrate that ON → Mi cell transmission exhibits a novel form of plasticity whereby high frequency synaptic activity induces selective LTP of NMDA receptor‐dependent spiking.
Neural Circuits for Taste: Excitation, Inhibition, and Synaptic Plasticity in the Rostral Gustatory Zone of the Nucleus of the Solitary Tracta
Authors: BRADLEY ROBERT M. , GRABAUSKAS GINTAUTAS
Published: February 2006

ABSTRACT: The rostral nucleus of the solitary tract (rNST) plays a key role in modulating, organizing and distributing the sensory information arriving at the central nervous system from gustatory receptors. However, except for some anatomical studies of rNST synapses, the neural circuits responsible for this first stage in synaptic processing of taste information are largely unknown. Over the past few years we have used an in vitro brain slice preparation of the rNST to study synaptic processing, and it has become apparent that the rNST is a very complex neural relay.

Synaptic potentials recorded in rNST neurons resulting from stimulation of afferent taste fibers are a composite of excitatory and inhibitory post synaptic potentials. Pure excitatory postsynaptic potentials (EPSP) can be isolated by using γ‐aminobutyric acid type A (GABAA) receptor blockers to eliminate the inhibitory postsynaptic potentials (IPSP). Application of glutamate ionotropic receptor blockers effectively eliminates all postsynaptic activity, indicating that glutamate is the transmitter at the first central synapse in the taste pathway. Stimulation of the afferent taste fibers originating from the anterior (chorda tympani) and posterior (glossopharyngeal) tongue results in a postsynaptic potential that is a complex sum of the two individual potentials. Thus, rNST neurons receive convergent synaptic input from the anterior and posterior tongue.

The IPSP component of the synaptic potentials in rNST results from stimulation of interneurons. If these IPSPs are initiated by tetanic stimulation they undergo both short‐term and long‐term changes. Short‐term changes result in the development of biphasic depolarizing IPSPs, and long‐term changes result in potentiation of the IPSPs that can last over an hr in some neurons. This remarkable synaptic plasticity may be involved in the mechanism of learned taste behaviors.

Synaptic transmission in rNST consists of excitation combined with inhibition. The inhibition does not simply depress excitation but probably serves many roles such as shaping and limiting excitation, coordinating the timing of synaptic events and participating in synaptic plasticity. Knowledge of these synaptic mechanisms is essential to understanding how the rNST processes taste information.
Ionic Mechanism of GABAA Biphasic Synaptic Potentials in Gustatory Nucleus of the Solitary Tracta
Authors: Grabauskas Gintautas , Bradley Robert M.
Published: February 2006

ABSTRACT: Gamma‐aminobutyric acid (GABA) is the principal neurotransmitter of synaptic inhibition in the gustatory nucleus of the solitary tract (rNST). High‐frequency activation of GABA neurons in the rNST results in biphasic inhibitory postsynaptic potentials (IPSPs) that are initially hyperpolarizing but then became depolarizing. Our results indicate that high‐frequency stimulation evokes redistribution of Cl− and K+ ions that shifts IPSP reversal potential in a more positive direction, which produces a biphasic or depolarizing IPSP.
Complex Functional Attributes of Amygdaloid Gustatory Neurons in the Rhesus Monkeya
Authors: KARÁDI Z. , SCOTT T. R. , OOMURA Y. , NISHINO H. , AOU S. , LÉNÁRD L.
Published: February 2006

ABSTRACT: To reveal specific functions of glucose‐sensitive (GS) and glucose‐insensitive (GIS) cells in chemical information processing, single neuron activity was recorded in the amygdaloid body (AMY) of macaques during: 1) gustatory stimulations and 2) microelectrophoretic administration of chemicals. Of the 629 neurons tested, 56 (8.9%) responded to, usually two or more, taste qualities. Hedonically distinct tastants usually elicited opposite firing rate changes of the gustatory cells. Seventy percent of the gustatory responses were recorded from GS neurons (17% of all AMY cells). Catecholamines (CAs) induced discharge rate changes in a majority of taste‐responsive neurons: The GS gustatory cells were suppressed by norepinephrine (in the form of noradrenaline HCl, NA), whereas the GIS taste‐responsive neurons were facilitated by dopamine (DA). Furthermore, NA‐ and/or DA‐antagonists were able to attenuate or suppress taste‐elicited responses of several of these cells. These and previous data indicate a specific functional organization of AMY gustatory cells: The GS and GIS taste neurons appear to be involved in differential integration of feeding‐associated humoral‐metabolic, motivational and exogenous chemical information.
Electrophysiological Responses to Bitter Stimuli in Primate Cortexa
Authors: SCOTT THOMAS R. , Giza Barbara K. , Yan Jianqun
Published: February 2006

ABSTRACT: Studies investigating fine details of gustatory coding in the domain of each basic taste quality have been completed for sweet, salt, and sour stimuli. In the present experiment, we used chemicals that humans describe as predominantly bitter. We recorded the activity of 50 taste neurons in insular cortex of two cynomolgus macaques. Stimuli were water, fruit juice, glucose, NaCl, HCl, and 16 bitter solutions. In a multidimensional taste space the 16 bitter stimuli formed a coherent cluster composed of three main subgroups: (1) QHCl, phenylalanine, theophylline, caffeine, propyl‐thiouracil (PROP), and phenylthiocarbamide (PTC), all of which humans describe as rather purely bitter, (2) MgCl2, CaCl2, NH4Cl, and arginine, which humans describe as salty‐bitter, and (3) urea, cysteine, and vitamin B1, which are described as sour‐bitter. Vitamin B2, histidine and nicotine were in the center of the bitter cluster. Human descriptions of taste qualities conformed well to the presumed quality of each stimulus as inferred from its position in the multidimensional space (MDS), reinforcing the use of the macaque as a neural model for human gustation.
Glomerular Cytoarchitectures in Chemosensory Systems of Arachnidsa
Authors: Brownell Philip H.
Published: February 2006

ABSTRACT: In most animals the central pathways of olfactory systems are associated with glomerular neuropil and lack topographic mapping of sensory inputs. Among arthropods, the insect and crustacean olfactory (antennal) pathways are typical examples. Two orders of chelicerate arthropods, the scorpions and solpugids (Cl. Arachnida), present striking exceptions to this generalization. The major chemosensory organs of scorpions are the pectines, two ventral appendages that contact the substrate intermittently as the animal searches for food or mates. In solpugids chemosensory input is from the antennalized pedipalps and first leg pairs, and from ten fan‐shaped malleoli extending ventrally to the substrate from the 4th leg pair. The pectinal and malleolar sensory systems have highly ordered arrangements of 105 to 106 primary chemoreceptors, with one (pectines) forming a two‐dimensional array and the other (malleoli) assembled in linear array. The spatial frequencies of these chemoreceptive inputs exceed 100/mm and 1000/mm, respectively, indicating a capacity for resolving structure of chemical deposits on substrates. Using several histological and axonal tracing techniques, the organization of pectinal and malleolar central projections has been resolved. The pectinal projection terminates posteriorly in the cephalothoracic mass and shows a high degree of topographic precision, perhaps to the level of individual receptors in the sensory field. This chemosensory 'map7' is imposed on laminar cytoarchitecture posteriorly in the brain but merges anteriorly into glomerular substructures. The sensory projection from the malleoli shows less topographic order with fewer and larger glomeruli reminiscent of the insect olfactory system. These comparisons between arthropod taxa suggest that olfactory projections are, to varying degrees, typically glomerular but may evolve topographic and laminar organization when the stimulus field is of fixed form.
Responses of Cockroach Antennal Lobe Projection Neurons to Pulsatile Olfactory Stimuli
Authors: LEMONA WILLIAM C. , Getz WAYNE M.
Published: February 2006

ABSTRACT: Behavioral evidence indicates that insects preferentially orient toward pulses of odorants as they occur downwind from a point source. Our recent results have shown that cockroach olfactory receptor neurons are able to reliably resolve 10‐Hz pulses of the general 'green' odorant 1‐hexanol, but it is unknown to what extent the central olfactory pathway is able to resolve temporal aspects of a general odor stimulus. In the present study, temporal response characteristics were measured in antennal lobe projection neurons of female American cockroaches, Periplaneta americana in response to series of short odor pulses (2.5‐20 Hz). Odor pulses were delivered to olfactory sensilla in a moving airstream controlled by electromagnetic valves and quantified by replacing the odorant with oil smoke and measuring the concentration of smoke passing through a light beam. The responses of projection neurons were recorded with an intracellular microelectrode placed in the projection neuron cell body. A variety of time courses of responses were recorded. Response patterns were consistent among identical stimuli within a neuron and varied among neurons. Some neurons increased spike frequency with stimulus onset while others decreased spike frequency. The latency to the change in spike frequency and the duration of the response also varied among neurons. Regardless of the temporal characteristics of the responses, nearly all projection neurons were able to resolve pulses of 1‐hexanol presented at 5 Hz and some could resolve 10‐Hz pulses. Thus, responses of antennal lobe projection neurons can reflect fine structures of non‐uniform distributions of general odorants in a turbulent odor plume. In addition, the variety of temporal response characteristics to identical stimuli suggests that odor quality is coded by a temporal code expressed across a population of projection neurons.
Sex Pheromones and Amino Acids Evoke Distinctly Different Spatial Patterns of Electrical Activity in the Goldfish Olfactory Bulba
Authors: HANSON LEAH R. , SORENSEN PETER W. , COHENC YOSEF
Published: February 2006

ABSTRACT: Until now, electrophysiological studies of the vertebrate olfactory bulb have tested only ‘generalist’ cues. These studies suggest that odorants are discriminated by a broadly distributed spatial map. In this study, we tested for the first time in a vertebrate the hypothesis that 'specialist' cues (Pheromones) are discriminated by a more restricted component of the olfactory bulb. Our model is the male goldfish, Carassius auratus, for which five sex Pheromones with both behavioral and physiological activity have now been identified. Electrical activity (electroencephalography: EEG) was recorded over a 12‐point grid from the surface of the olfactory bulb, while fish were exposed to one of ten stimuli including: five sex Pheromones, two amino acids, two bile steroids and a control. Evoked activity was evaluated by time series analysis. Power ratios were calculated by dividing the power of the dominant frequency in the power spectrum before stimulation, by the power of the dominant frequency during stimulation. Next, the average magnitudes of odorant responses were compared using analysis of variance (ANOVA). The spatial patterning of these responses was also described using cluster analysis, which grouped odorants based on the similarity of their spatial patterns of activity. Although all odorants elicited EEG responses with similar dominant frequencies, odorant‐specific differences were evident in the size and distribution of these responses. Sex Pheromones and bile steroids elicited relatively small responses that were spatially restricted in distinctive manners, although some overlap was evident. In contrast, amino acids consistently produced large responses at all positions. These results are consistent with the hypothesis that vertebrate Pheromones are discriminated by a distinctive subcomponent of the vertebrate olfactory system comprised of a relatively small number of olfactory neurons.
Central Processing of Aggregation Pheromones in Solitary and Gregarious Desert Locusts, Schistocerca gregariaa
Authors: ANTON SYLVIA , HANSSON BILL S.
Published: February 2006

ABSTRACT: In the desert locust, Schistocerca gregaria, a number of behaviorally active aggregation Pheromone components have been identified from adult male S. gregaria, and from third, fourth and fifth instar nymphs. Adult females seem not to produce aggregation Pheromones. Adult males and females, but not nymphs respond to the adult male‐produced mixture, whereas only nymphs respond to the binary nymph‐produced mixture with aggregation behavior. We studied the structure and function of antennal lobe interneurons, responding to single aggregation Pheromone components and adult‐ and nymph‐specific mixtures. Neurons in adult males and females and in first instar nymphs of S. gregaria in the solitary and the gregarious phase were investigated. Projection neurons responded with different degrees of specificity to all behaviorally active aggregation Pheromone components. Component‐specific, blend‐specific and generalist neurons were found in adults and first instar nymphs in both phases. Antennal lobe neurons were slightly more sensitive in solitary than in gregarious locusts. In gregarious adult males and females more neurons responded to the adult male mix than to any of the single components. In gregarious first instar nymphs most neurons responded to the adult male mix and the major component but also nymph mix specific neurons were found. The behavior of adults and nymphs is thus partially reflected by the response characteristics of antennal lobe projection neurons.
Mitral Cells and Ruffed Cells: Two Physiologically Different Types of Relay Neurons in the Offactory Bulb of Goldfisha
Authors: ZIPPEL H. P.
Published: February 2006

ABSTRACT: Anatomical differences characterizing mitral cells (MC) and ruffed (RC) cells were published 10‐15 years ago by Kosaka and Hama in three teleost species (goldfish, catfish and sea eel). Physiological responses from the two different types of relay neurons were recorded extracellularly and simultaneously in the plexiform layer using a single tungsten microelectrode electrode (A‐M systems 5770; 10‐12 MW). During interstimulus intervals MC responded with higher, frequently burst‐like impulse rates (mean value 2.7 s−1) triggered by the activity of epithelial receptor neurons. The MC activity could be totally suppressed during anesthesia of the epithelium. RC impulse rates were low (mean value 0.75 s−1), and each potential triggered a long‐lasting (3‐5 ms), continuously variable, summed granule cells (GC) potential (∼3 ms peak to peak). MC activity via GC laterally inhibited RC potentials. In contrast to MC, blockade of epithelial receptor cells increased the activity of RC. During olfactory stimulation (nonfamiliar stimuli: amyl acetate, β‐ionone, 2‐phenylethanol 10−6 M; relevant natural stimuli: four amino acids 10−6‐10−10 M; preovulatory Pheromone 17,20β‐dihydroxy‐4‐pregnen‐3‐one 10−9‐10−13 M, bile acid taurolithocholic acid, 10−6‐10−10 M) contrasting interactions between MC and RC were present that even in the lowest concentration resulted in a drastic intensification of centrally transmitted information. More frequently an inhibition was recorded from MC, and decreasing lateral inhibition via GC resulted in an activation of RC. Activation of RC resulted in an activation of pools of GC via initial pedunculate protrusions from the long unmyelinated portion of their axons, laterally inhibiting pools of MC in their vicinity.