Biomedical subjects

D V Smith

Publications and source records attributed to D V Smith.

At least 37 records · Page 2Linked to original sources

PubMed1997

Amiloride effects on taste quality: comparison of single and multiple response category procedures.

Although there is compelling evidence that amiloride reduces the intensity of Na+ and Li+ salts in humans, its effects on saltiness are conflicting. Many salts elicit not only a salty taste but also one or more side tastes (sweetness, sourness or bitterness). Some studies have shown a suppression of saltiness by amiloride; others show no effect on saltiness but a significant reduction in sourness. In the experiments demonstrating a reduction of saltiness, subjects estimated only saltiness; in those showing an amiloride effect on sourness and not saltiness, subjects estimated all qualities on each trial. The present study examines the role of the psychophysical method in these conflicting results. We have investigated the effects of amiloride on taste quality by modifying only the instructions to the subjects, keeping all other variables constant. One group of subjects (intensity-only) gave magnitude estimates of the overall intensity of a LiCl concentration series. A second group (salty-only) was instructed to estimate the saltiness of the stimuli, and a third group (sour-only) estimated their sourness. Finally, a fourth group (profile) rated all of the taste qualities on each stimulus presentation, using a modified taste profile method. The ratings of all groups were made comparable by the use of 0.1 mM quinine-HCl as a modulus. When subjects used only one response category, amiloride reduced their estimates (of intensity, saltiness or sourness), but if subjects attended to all four qualities, amiloride specifically reduced the sourness of LiCl and had no significant effect on its saltiness. Comparison of the saltiness estimates of the salty-only group to the sum of the salty and sour estimates of the profile group demonstrated that subjects combined these sensations when presented with only one response alternative. To reveal the effect of amiloride on a specific quality of a salt, the psychophysical method must allow subjects to attend to all qualities on each trial. These data and previous results suggest that apical Na+ channels on the taste receptor cell membrane mediate the sourness but not the saltiness of Na+ and Li+ salts.

Amiloride↗

PubMed1997

Glutamate receptor antagonists block gustatory afferent input to the nucleus of the solitary tract.

The effects of excitatory amino acid (EAA) receptor antagonists in blocking the synaptic transmission between gustatory fibers of the chorda tympani (CT) nerve and taste-responsive neurons within the nucleus of the solitary tract (NST) were examined electrophysiologically in urethan-anesthetized hamsters. Single neurons in the NST were recorded extracellularly and drugs were microinjected into the vicinity of the cell with the use of a multibarrel pipette assembly. The activity of each cell was recorded in response to lingual stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid, 0.032 M quinine hydrochloride, and/or 25 microA anodal current pulses. Once a cell was identified as a taste-responsive neuron, one or more EAA receptor antagonists were administered by microinjection. Approximately 27 nl of 50 mM kynurenic acid (KYN), a broad-spectrum EAA receptor antagonist; 0.5 or 2.0 mM DL-2-amino-5-phosphonovalerate (APV), an N-methyl-D-aspartate (NMDA) receptor antagonist; 0.05 or 0.5 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist; or phosphate-buffered physiological saline was applied to the neuron. Responses to chemical stimulation of the anterior tongue were obtained before and after drug administration and again after recovery; responses to anodal current stimulation (0.1 Hz) were obtained continually throughout the drug administration protocol. Microinjection of KYN completely and reversibly abolished responses elicited by both anodal current and chemical stimulation of the anterior tongue. The excitatory responses of cells in the NST to chemical and electrical stimulation of the anterior tongue were also completely and reversibly blocked by CNQX, implicating the involvement of an AMPA/kainate receptor. Microinjection of APV was generally less effective and partially reduced the responses of some taste-responsive NST cells to chemical stimulation of the anterior tongue. There were no effects following microinjection of a 27-nl bolus of phosphate-buffered saline. None of these EAA receptor antagonists had a differential effect on responses to different taste stimuli. The responses to all tastants were completely blocked by both KYN and CNQX; there was no apparent relationship between the response to any particular tastant and the limited effects of APV. These data implicate glutamate as an excitatory neurotransmitter between CT gustatory fibers and taste-responsive NST cells and suggest that it acts primarily on AMPA/kainate receptors, with some contribution from NMDA receptors. This conclusion is strengthened by other data obtained from in vitro slice preparations, which show that responses of cells in the rostral NST to solitary tract stimulation are blocked by both NMDA and AMPA/kainate receptor antagonists.

Animals↗

PubMed1996

Distribution and synaptology of glossopharyngeal afferent nerve terminals in the nucleus of the solitary tract of the hamster.

The distribution and synaptology of the afferent fibers of the glossopharyngeal nerve (IXN) in the hamster were studied by using horseradish peroxidase (HRP) histochemistry visualized with light and electron microscopy. Crystals of HRP were applied to the trunk of IXN in the vicinity of the petrosal ganglion. The densest IXN afferent label was distributed within the nucleus of the solitary tract (nst), just caudal to but overlapping with the area of termination of the facial nerve. Labeled IXN fibers extended rostrally to the principal trigeminal nucleus and caudally to the cervical spinal cord. There was significant labeling within the spinal trigeminal complex; the area postrema and the medullary reticular formation contained some labeled fibers. Ultrastructurally, the synaptic arrangements of anterogradely labeled IXN fibers were examined in the nst. Quantitative measures were taken of the area, maximum diameter, perimeter, and vesicles of labeled endings and the length of their synaptic junctions with dendritic processes. These endings were compared to comparable endings in control material and to published descriptions of VIIth nerve afferent terminals in the hamster nst. The synaptic relations of IXN afferent endings were predominantly with dendritic spines and shafts. The majority (86.6%) of IXN afferent endings were with dendritic processes that were not in apparent contact with other, unlabeled processes. Only 13.4% of IXN synaptic relationships were with dendritic processes that were also contacted by unlabeled vesicle-containing processes. This is in contrast to 31.2% of facial nerve afferent endings in the nst which make synaptic contact with such processes. There were more direct synaptic contacts between facial endings and unlabeled vesicle-containing processes (26.1%) than between IXN endings and unlabeled vesicle-containing processes (1.3%). Thus, unlike the glomerular-like endings of the gustatory fibers of the VIIth nerve, less complex relations appeared to characterize IXN synapses in the nst. These differences were related to the differential physiology of gustatory fibers in the VIIth nerve and IXN.

Afferent Pathways↗

PubMed1996

Amiloride suppresses the sourness of NaCl and LiCl.

The transduction of Na+ salts in many species is mediated by both apical and submucosal ion channels on the taste receptor-cell membrane. The apical ion channel is blockable by the diuretic amiloride, whereas the submucosal pathway is not. Previous human psychophysical studies have shown a decrease in NaCl taste intensity caused by amiloride that is smaller than the reduction of the electrophysiological response produced by amiloride in other species. Many salts, including NaCl, elicit not only a salty taste to humans, but also sweet, sour, or bitter side tastes. Amiloride has been shown to reduce the sourness, but not the saltiness, of NaCl and Na gluconate and to have no effect on the taste of KCl. The present experiment further evaluated the hypothesis that the sour taste of Na+ and Li+ salts is mediated by the amiloride-sensitive transduction mechanism, by examining the effect of amiloride on the taste of LiCl, which is considerably more sour than NaCl. Four concentrations of NaCl, LiCl, and KCl were presented to the anterior tongue following adaptation to water or after 10 microM amiloride treatment. Subjects estimated the intensity of the taste of each stimulus and divided this estimate among the appropriate taste qualities. There was a significant decrease in the total taste intensity of NaCl and LiCl after amiloride, but no effect on KCl; LiCl was more greatly suppressed than NaCl. These data show no effect on the saltiness of LiCl or NaCl, except for a small reduction in the saltiness of 0.1 M NaCl. On the contrary, there was a significant effect on the sourness of both NaCl and LiCl. Citric acid (3.2 mM) was also used as a stimulus, but amiloride treatment had no effect on its sourness. These data indicate that the amiloride-sensitive channel plays a key role in the perception of the sour taste of NaCl and LiCl (but not citric acid) and little role in the perception of saltiness. The salty taste of these salts may arise from other transduction pathways.

Adult↗

PubMed1996

Responses of gustatory cells in the nucleus of the solitary tract of the hamster after NaCl or amiloride adaptation.

1. The responses of single nucleus of the solitary tract (NST) neurons in the hamster were recorded to an array of Na+ and non-Na+ stimuli under each of three adaptation conditions: distilled H2O, 0.032 M NaCl, and 10 microM amiloride. Each adapting solution flowed for 60 s before delivery of one of seven test stimuli: 0.032 M NaCl, NaNO3, and Na-gluconate, 0.1 M KCl and sucrose, 1 mM HCl, and 3 mM quinine hydrochloride (QHCl). Stimuli were dissolved in distilled H2O (H2O and NaCl adaptation conditions) or 10 microM amiloride (amiloride adaptation condition). 2. Both amiloride treatment and NaCl adaptation reduced responses to the Na+ stimuli. The effects of NaCl adaptation were generally greater than those of amiloride, and the responses to the Na+ salts were reduced by NaCl adaptation in every cell that responded to NaCl, regardless of its best-stimulus classification. Amiloride treatment suppressed the responses to Na+ salts with larger anions (NaNO3 and Na-gluconate) more than the response to NaCl. 3. Unlike amiloride treatment, NaCl adaptation also reduced responses to several non-Na+ stimuli (KCl, HCl, and QHCl). This effect occurred primarily in the NaCl-best neurons that were most highly responsive to NaCl and that showed a postexcitatory suppression after NaCl. This suppression has been observed in recordings from the chorda tympani nerve in both rats and hamsters and in taste receptor cell responses recorded in situ in the rat. If it is a receptor phenomenon, these data would imply that some NaCl-sensitive receptor cells are also responsive to these non-Na+ electrolytes. 4. The effects of amiloride on the responses to Na+ stimuli were not limited to NaCl-best neurons, but occurred in sucrose-best cells as well. These results suggest that the sucrose-best cells in the NST receive converging input from sucrose- and NaCl-best chorda tympani fibers, because there is little Na+ sensitivity in the peripheral sucrose-best fibers and the amiloride sensitivity is restricted to NaCl-best chorda tympani fibers. The responses to NaCl in the few HCl- and QHCl-best NST neurons were not affected by amiloride. 5. Rinsing the tongue with amiloride for 60 s resulted in a reduction in the baseline response rate of NST cells. This effect occurred primarily in NaCl- and sucrose-best NST neurons and implies that much of the spontaneous activity in these brain stem cells arises from amiloride-sensitive channel activity in the peripheral receptor cells. 6. The results of human psychophysical studies show very different effects of NaCl adaptation and amiloride treatment. Adaptation to NaCl produces a robust and specific reduction in the saltiness of all salts. The present results show that NaCl adaptation reduces the responses of all cells sensitive to NaCl. Treatment of the human tongue with amiloride produces a proportionately smaller reduction in the response to NaCl than it does in rodents, and it appears to have no effect on saltiness. Rather, amiloride has been shown to specifically reduce the sour side taste of NaCl, Nagluconate, and LiCl. Therefore conclusions about the effects of amiloride on taste quality based on rodent electrophysiology are questionable.

Adaptation, Physiological↗

PubMed1995

Evaluation of the medical diagnostic imaging support system based on 2 years of clinical experience.

The Medical Diagnostic Imaging Support (MDIS) system at Madigan Army Medical Center (MAMC) has been operational in a phased approach since March 1992. Since then, nearly all image acquisition has been digital with progressively increasing primary softcopy diagnosis used. More than 375,000 computed radiography (CR) images as well as other modality images have been archived. Considerable experience in installation and implementation phasing has been gained. The location and ergonomic aspects of equipment placement were refined with time. The original clinical scenario was insufficiently detailed and additions were made to facilitate smoother and more complete transition toward a filmless environment. The MDIS system effectiveness and performance have been good in terms of operational workload throughout, background operations, and reliability. The important areas regarding reliability are image acquisition, output, display, database operations, storage, and the local area network. Fail-safe strategies have been continually improved to maintain continuous clinical image availability during the times when the MDIS system or components malfunction. Many invaluable lessons have been learned for effective quality assurance in a hospital-wide picture archiving and communication system. These issues include training, operational quality control, practical aspects of CR image quality, and increased timeliness in the generation and distribution of radiographic reports. Clinical acceptability has been a continuous process as each phase has been implemented. Clinical physicians quickly used the workstations soon after the start of MDIS at MAMC. The major advantage for clinicians has been the amount of time saved when retrieving multimodality images for review. On the other hand, the radiologists have been slower in their acceptance of the workstation for routine use.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers↗

PubMed1995

Amiloride suppression of the taste intensity of sodium chloride: evidence from direct magnitude scaling.

The transduction of Na+ salts has been shown in many species to be mediated in part by an epithelial ion channel on the apical surface of the taste receptor cell membrane, which is blockable by the diuretic amiloride. In addition to this apical ion channel, Na+ is also transduced via a paracellular pathway, which is not sensitive to amiloride. There are significant species differences in the contribution of the amiloride-sensitive pathway to Na+ transduction. Previous human psychophysical studies have reported conflicting results on the effects of amiloride in suppressing the intensity of NaCl. In general, these studies used amiloride doses that were much higher than those showing clear suppressive effects in electrophysiological studies in other species. In the present experiment, we used direct magnitude scaling of the intensities of five NaCl concentrations flowed over the anterior portion of the tongue to determine the effects of amiloride treatment at lower doses. NaCl was presented after adaptation of the tongue to water or mixed with and presented after adaptation to 10, 50, or 100 microM amiloride-HCl. Subjects estimated the intensity of NaCl and of these concentrations of amiloride in each treatment condition using magnitude estimation with a 0.1 M NaCl modulus presented following a water rinse prior to each session. Results showed that amiloride had a significant suppressive effect on the perceived intensity of NaCl, with a similar effect seen at all three amiloride doses. The psychophysical function after amiloride showed a parallel shift to the right. The average suppression over all NaCl concentrations was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Taste quality profiles for fifteen organic and inorganic salts.

Biophysical studies of isolated taste receptor cells show that one transduction mechanism for Na+ salts involves the inward movement of Na+ through an apical ion channel, which is sensitive to the diuretic amiloride. An additional paracellular pathway also appears to be involved in NaCl transduction, but not in the transduction of organic Na+ salts. Little is known, however, about how these receptor mechanisms relate to taste perception. Recent human psychophysical studies suggest that the amiloride-sensitive transduction pathway is coupled to the sour side taste of these salts rather than to their saltiness. In the present study, we employed direct magnitude estimation of taste intensity and quality of fifteen organic and inorganic Na+, Li-, K+, and Ca+2 salts. Many salts had multiple taste qualities, such as the salty and bitter tastes of NH4Cl and KCl; the Ca+2 salts were predominantly bitter. Taste quality often changed with stimulus concentration. Multivariate analyses of their taste profiles resulted in a grouping of these 18 stimuli within a taste space bounded by NaCl, sucrose, citric acid, and QHCl, with the organic salts positioned between NaCl and citric acid. The organic Na+ salts and the Li+ salts were considerably less salty and proportionately more sour than NaCl. These results, combined with previous work showing that amiloride suppresses the sourness of NaCl and Na-gluconate, predict that the organic Na+ salts and the Li+ salts would be more greatly suppressed by amiloride treatment than would NaCl.

Adult↗

PubMed1995

Effect of amiloride on the taste of NaCl, Na-gluconate and KCl in humans: implications for Na+ receptor mechanisms.

Sodium-salt transduction in many species may be mediated by both apical and submucosal ion channels on the taste receptor cell membrane. The apical ion channel is blockable by the diuretic amiloride, whereas the submucosal pathway is not. Sodium salts with small anions, such as NaCl, can stimulate submucosal as well as apical ion channels; sodium salts with large anions, such as Na-gluconate, activate primarily the apical channels. In humans, reports on the effects of amiloride on the taste of NaCl are conflicting and no data exist on the effects of amiloride on organic sodium salts. In the present experiment, subjects gave magnitude estimates of the total intensity and of each of the basic taste qualities for NaCl, Na-gluconate and KCl. Five concentrations of each of these stimuli were presented to the anterior tongue following distilled water adaptation and after amiloride treatment. There was a significant decrease in the total taste intensity of NaCl and Na-gluconate after amiloride, but no effect on KCl. The saltiness of all three salts was unaffected, but amiloride decreased the perceived sourness of the sodium salts. KCl sourness was unaffected by amiloride. There was a proportionately larger effect of amiloride on Na-gluconate than on NaCl, which is consistent with a larger role for the apical ion channel in Na-gluconate transduction. However, an appreciable amiloride-insensitive component is present for both NaCl and Na-gluconate, suggesting that an amiloride-insensitive pathway also plays a role in the transduction of both sodium salts. These data support the hypothesis that an amiloride-sensitive transduction component exists in humans, but suggest that it is considerably smaller than in many other species.

Amiloride↗

PubMed1995

The perception of saltiness is eliminated by NaCl adaptation: implications for gustatory transduction and coding.

The tastes of salts to humans are complex. NaCl is the most purely salty of all salts, but even this stimulus tastes sweet at low concentrations and somewhat sour at mid-range intensities. Other salts taste significantly sour or bitter in addition to salty. Previous studies have shown that the saltiness of simple halide salts is reduced by adaptation to NaCl, suggesting that a single mechanism might be responsible for the salty taste of these stimuli. In electrophysiological studies in rodents, the response to NaCl is reduced by application to the tongue of the Na(+)-channel blocker amiloride. Organic Na+ salts are more heavily dependent on this amiloride-sensitive transduction component than NaCl, and are generally less salty and more sour. In order to investigate the relationship between NaCl saltiness and that evoked by other salts, we adapted the tongue to distilled H2O and to 0.1 M NaCl and obtained direct magnitude estimates of the taste intensity of 15 organic and inorganic Na+, Li+, K+ and Ca2+ salts, matched for total intensity. Subjects divided these magnitude estimates among the component taste qualities. Adaptation to NaCl abolished the taste of NaCl and LiCl, and eliminated the saltiness of all other salts. The magnitude estimates of the bitterness and sourness of many salts increased after NaCl adaptation. Since recent biophysical data suggest that adaptation in taste receptors may involve whole-cell mechanisms, we propose that saltiness is reduced by NaCl adaptation because it originates in the subset of taste receptors responsive to NaCl. This implies that saltiness is coded within the CNS in cells whose receptive fields include the NaCl-sensitive receptor cells and that the degree to which any salt tastes salty is determined by its ability to drive these receptors. This model proposes, for example, that KCl has a salty component because it stimulates some of the same receptor cells as NaCl, even though the transduction mechanisms for KCl are different than those engaged by NaCl. Adaptation to NaCl blocks the saltiness of KCl and other salts because they stimulate NaCl-sensitive receptor cells.

Adaptation, Psychological↗

PubMed1994

Expression of the neural cell adhesion molecule (NCAM) and polysialic acid during taste bud degeneration and regeneration.

Taste receptor cells are replaced throughout life, accompanied by continuing synaptogenesis between newly formed taste cells and first-order gustatory fibers. The neural cell adhesion molecule (NCAM) is expressed by a subset of taste cells in adult rodents and appears on gustatory nerve fibers during development prior to differentiation of the taste buds. We employed antibodies against the extracellular domain of the NCAM polypeptide (mAb 3F4) and against polysialic acid (PSA) residues found on embryonic forms of NCAM (mAb 5A5) to investigate the relationship between the expression of these molecules and the innervation of taste buds in adult rats. In unoperated rats, anti-NCAM recognized a subset of cells within the vallate taste buds and also the fibers of the glossopharyngeal (IXth) nerve, including those innervating the gustatory epithelium. Taste bud cells did not express PSA but mAb 5A5 immunoreactivity was observed on some fibers of the IXth nerve, including a few that entered the taste buds. Bilateral crush of the IXth nerve resulted in the loss of NCAM expression from the gustatory epithelium within 8 days. As IXth nerve fibers reinnervated the epithelium, NCAM expression was seen first in the nerve, followed by increased expression in the epithelium as the taste cells differentiated from their precursors. PSA expression by fibers of the IXth nerve did not return to normal until well after the regeneration of the vallate taste buds. The present results demonstrate that taste cell expression of NCAM is dependent upon innervation by the IXth nerve and that NCAM expression appears in the nerve prior to its expression in the differentiating epithelium during regeneration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Taste bud expression of human blood group antigens.

Some human blood group antigens are expressed by rodent epithelial cells at different stages of differentiation. Since adult taste cells are continually replaced throughout life, we investigated the expression of the H, B, A and Lewisb blood group determinants by cells of the rat fungiform, foliate and vallate papillae. We employed antibodies against the trisaccharide structures of the H, B, and A blood group antigens and against the Lewisb blood group epitope in studies of normal and denervated taste buds. The antibody against the H antigen reacted with the majority of cells in all taste buds and with cells in the spinous layer of the tongue epithelium. The B antigen was expressed by the majority of taste cells but not by other epithelial cells. The expression of the A antigen was significantly less in the fungiform taste buds than in the vallate or foliate taste buds. The A antigen was also abundantly expressed in the acini of the lingual salivary glands. The Lewisb epitope was expressed by a subset of cells in taste buds of the fungiform, foliate and vallate papillae. Taste buds are trophically dependent upon gustatory nerve innervation. Transection of the chorda tympani or the IXth nerve resulted in the loss of expression of these molecules from the gustatory epithelium, indicating that they are expressed only on differentiated taste cells. The blood group antigens are lactoseries carbohydrates; they are differentially expressed in developing cochlear hair cells and olfactory neurons and may play roles in cell-cell recognition, adhesion, and other interactions important in the developing nervous system. They could have similar functions in the taste and olfactory systems, where the receptors are continually renewed and new synapses between the receptors and their neural targets continually form.

ABO Blood-Group System↗

PubMed1994

Neural coding of aversive and appetitive gustatory stimuli: interactions in the hamster brain stem.

There is increasing evidence, both electrophysiological and behavioral, that bitter and sweet stimuli drive parallel pathways in the gustatory brainstem. Here we report two lines of investigation that suggest significant interactions among these parallel systems. First, responses recorded from single cells in the hamster's parabrachial nuclei (PbN) show that quinine hydrochloride (QHCl) produces a substantial suppression (> 40%) of the responses of PbN cells to sucrose. Sucrose stimulation has a reciprocal suppressive effect on the response to QHCl. These results imply that aversive and appetitive stimuli produce mutual inhibition in the gustatory system; studies of the chorda tympani nerve response suggest that this inhibition likely arises within the brainstem. A second line of investigation, using both an in vitro brainstem slice preparation and in vivo pharmacological manipulations of cells in the hamster NST, has demonstrated an inhibitory network within the rostral NST that plays a role in the modulation of taste activity. Patch-clamp and extracellular recording studies in vitro show that cells within the rostral central subdivision of the NST are inhibited by gamma-aminobutyric acid (GABA); this mediation is largely through the GABAA receptor subtype. Here we show that responses to taste stimulation recorded extracellularly from NST cells in vivo can be inhibited by local microinjections of GABA; this inhibition is blocked by the GABAA receptor antagonist bicuculline methiodide. Responses to sucrose are significantly more inhibited than those to NaCl or KCl. These combined lines of evidence show that appetitive and aversive stimuli activate mutually inhibitory systems within the brainstem and suggest that the basis for this interaction is a GABAergic inhibitory network within the NST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Responses of single hamster parabrachial neurons to binary taste mixtures of NaCl with sucrose or QHCl.

1. Although human psychophysical responses to taste mixtures have been investigated extensively, there have been few reports on the neurophysiological coding of taste mixtures in the mammalian gustatory system. In recent studies we have investigated the responses of single third-order neurons in the hamster parabrachial nucleus (PbN) to anterior tongue stimulation with binary mixtures of heterogenous taste stimuli including sucrose+QHCl, sucrose+citric acid, and NaCl+citric acid. Some of these stimulus combinations evoked mixture suppression, or response frequencies that were less than that evoked by the more effective component (MEC) presented alone, which is analogous to the mixture suppression reported in human psychophysical studies of similar taste mixtures. In the current report we extend our investigation to include NaCl+QHCl and NaCl+sucrose mixtures. 2. The action potentials of single PbN neurons were recorded extracellularly. Four concentrations of each stimulus were employed: NaCl and sucrose at 0.001, 0.01, 0.1, and 1.0 M; QHCl at 0.00032, 0.0032, 0.032, and 0.1 M. All stimuli were tested alone and in mixture; the NaCl+sucrose and NaCl+QHCl mixtures were formed by pairing the four concentrations of each stimulus with the strongest concentration of the other stimulus. 3. For both NaCl+sucrose and NaCl+QHCl mixtures, the response frequencies evoked by the mixtures did not differ from those evoked by the MEC presented alone, whether averaged across all neurons or across subgroups of NaCl- or sucrose-best cells. Furthermore, the across-neuron patterns (ANPs) of mixture responses were similar to those of the MECs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

NCAM expression by subsets of taste cells is dependent upon innervation.

The expression of the neural cell adhesion molecule (NCAM) and distinct carbohydrate groups by cells of the taste buds of the rat vallate papilla was investigated by immunohistochemical and biochemical techniques. We employed antibodies against 1) the extracellular (mAb 3F4) and cytoplasmic (mAb 5B8) portions of the NCAM polypeptide, 2) the highly sialylated form of NCAM (mAb 5A5), 3) carbohydrate epitopes associated with glycosylated NCAM forms in the rat (mAb 2B8) or frog (mAb 9-OE) olfactory system, and also 4) the Lewisb blood group carbohydrate epitope (mAb CO431). NCAM mRNA was demonstrated by polymerase chain reaction (PCR) in samples of the vallate papilla, suggesting the presence of NCAM in cells of the taste buds. Antibodies against NCAM (mAbs 3F4 and 5B8) recognized a subset (about 20%) of cells within the vallate taste buds; fibers of the glossopharyngeal nerve, including those innervating the gustatory epithelium, were NCAM immunoreactive. Taste bud cells did not express polysialic acid (mAb 5A5), but mAb 5A5 immunoreactivity was observed on fibers of the IXth nerve, including a few that entered the taste buds. All or nearly all of the cells within the vallate taste buds were immunoreactive to mAb 2B8, whereas mAbs 9-OE and CO431 reacted with subsets of cells. The carbohydrates recognized by mAbs 2B8 and 9-OE were also abundantly expressed in the ducts and acini of the lingual salivary glands. Bilateral crush of the IXth nerve resulted in the loss of expression of all of these molecules from the gustatory epithelium. If cells of the taste bud express NCAM during their final stage(s) of differentiation, then NCAM could play a role(s) in the growth of gustatory axons toward their target epithelial cells and in the recognition between the nerve fibers and mature taste receptor cells, or among the taste bud cells themselves.

Animals↗

PubMed1993

Responses of single hamster parabrachial neurons to binary taste mixtures: mutual suppression between sucrose and QHCl.

1. Although taste experience typically arises from a mixture of gustatory stimuli, nearly all previous neurophysiological studies of the mammalian central gustatory system have focused on responses to single chemical stimuli. To begin to systematically examine CNS responses to taste mixtures, we recorded the extracellular activity of single third-order neurons in the hamster PbN to anterior tongue stimulation with binary mixtures of sucrose and QHCl. In experiment 1, neurons were tested with four concentrations of sucrose (0.001, 0.01, and 1.0 M) presented alone and mixed with 0.1 M QHCl. In experiment 2, neurons were tested with four concentrations of QHCl (0.00032, 0.0032, 0.032, and 0.1 M) presented alone and mixed with 1.0 M sucrose. 2. The response to each binary mixture was compared with the response to the more effective component (MEC) presented alone, and those that differed by more than a selected criterion (based on response variability) were identified. Of all mixture responses, 37% (59/158) involved mixture suppression (mixture response < MEC response), only 4% (6/158) were greater than the MEC, and 59% (94/158) were classified as not different than the response to the MEC. Most neurons that displayed mixture suppression did so at several mixture concentrations. 3. Sucrose suppression (mixture response < sucrose response) was prevalent among neurons most responsive to sucrose and for the mixtures that contained the stronger sucrose concentrations. Among neurons that displayed sucrose suppression, the magnitude of suppression was significantly correlated with sucrose response magnitude but not with QHCl response magnitude. These and other factors suggest that a neuron's capacity to display sucrose suppression to sucrose+QHCl mixtures is related to its sucrose sensitivity. 4. QHCl suppression (mixture response < QHCl response) was less prevalent than sucrose suppression, and the neurons that displayed QHCl suppression were almost exclusively a subset of those that displayed sucrose suppression to the same or different mixtures. This finding and the observation that one-third of all mixture responses involved mutual suppression (response to the mixture less than that to either component alone), suggest an association between the factors underlying sucrose suppression and QHCl suppression. 5. The across-neuron patterns (ANPs) of taste responses, which are thought to represent taste quality, were compared for mixtures and components. In general, the ANP for each mixture was similar to (significantly correlated with) the ANP of the more stimulatory component. However, for the mixture that evoked the greatest sucrose suppression, the mixture ANP was more similar to the ANP of the less stimulatory component.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1993

Responses of single hamster parabrachial neurons to binary taste mixtures of citric acid with sucrose or NaCl.

1. Although taste experience generally arises from a mixture of gustatory stimuli, most neurophysiological studies of the mammalian central gustatory system have focused on responses to single chemical stimuli. Recently, in a study of single third-order neurons in the hamster parabrachial nucleus (PbN), we reported that mixture suppression occurs in the responses to binary mixtures of sucrose and QHCl presented to the anterior tongue. Mixture suppression was reflected both in reduced response frequencies and in an altered pattern of responses across neurons. In the current report we extend our investigation of CNS neuron responses to binary mixtures of heterogeneous stimuli to include sucrose+citric acid mixtures and NaCl+citric acid mixtures. The response to each mixture was compared with the response to the more effective component (MEC) presented alone, and those that differed by more than a selected criterion (based on response variability) were identified. 2. For all mixture responses recorded, 29% (79/256) involved mixture suppression (mixture response < MEC response), only 6% (18/276) were greater than the response to MEC, and 65% (179/276) did not differ from the response to the MEC. 3. In Experiments 1 and 2, neurons were tested with four concentrations of sucrose or citric acid each presented alone and in binary mixtures with a single strong concentration of the other stimulus. Sucrose suppression (mixture response < sucrose response) occurred in 24% of mixture responses and was exhibited almost exclusively by sucrose-best neurons, primarily to the mixtures that contained the stronger sucrose and citric acid concentrations. Sucrose suppression involved a 40% reduction of mixture response frequencies compared with responses to the sucrose component alone. 4. In Experiments 3 and 4, neurons were tested with four concentrations of NaCl or citric acid each presented alone and in binary mixtures with a single strong concentration of the other stimulus. NaCl suppression (mixture response < NaCl response) occurred in 21% of mixture responses and was displayed by both sucrose-best and NaCl-best neurons. NaCl suppression involved a 28% reduction in mixture response frequencies compared with responses to the NaCl component alone. In all experiments citric acid suppression (mixture response < citric acid response) was observed in only 6% of mixture responses and was relatively small in magnitude. 5. The across-neuron patterns (ANPs) of taste responses, which are correlated with behavioral measures of taste similarity, were compared for mixtures and components.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1992

Human olfactory biopsy. The influence of age and receptor distribution.

Thirty-six mucosal specimens were obtained with a biopsy instrument from the upper nasal septum of 12 human autopsy cases before the en bloc removal of the entire olfactory area. Examination of these 36 specimens with transmission electron microscopy demonstrated olfactory epithelium in only 17. A significant negative correlation (r = -.728) was noted between the age of the subject and the probability of obtaining olfactory epithelium, supporting the idea that the olfactory mucosa is gradually replaced by respiratory epithelium with aging. Using the en bloc specimens, the distribution of olfactory epithelium was reconstructed from light microscopic examination of silver-stained sections. Multiple patches of respiratory epithelium were observed over the upper portion of the nasal septum and superior turbinates, ie, the presumptive olfactory area. On transmission electron microscopic examination, frequent respiratory metaplasia was also suggested. Within the area of respiratory metaplasia, supporting cell-like and microvillar cell-like structures often were found; these structures may be remnants of olfactory epithelium. The sampling of olfactory tissue with a biopsy procedure is hampered by the irregular and patchy distribution of olfactory epithelium. The invasion of respiratory epithelial patches into the olfactory mucosa seems to be characteristic of the human olfactory epithelium and may increase as a function of age. Thus, conclusions about the structure of the olfactory mucosa in an individual patient must be based on several tissue samples.

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