Mapping social reward and punishment processing in the human brain: A voxel-based meta-analysis of neuroimaging findings using the social incentive delay task.

Social rewards or punishments motivate human learning and behaviour, and alterations in the brain circuits involved in the processing of these stimuli have been linked with several neuropsychiatric disorders. However, questions still remain about the exact neural substrates implicated in social reward and punishment processing. Here, we conducted four Anisotropic Effect Size Signed Differential Mapping voxel-based meta-analyses of fMRI studies investigating the neural correlates of the anticipation and receipt of social rewards and punishments using the Social Incentive Delay task. We found that the anticipation of both social rewards and social punishment avoidance recruits a wide network of areas including the basal ganglia, the midbrain, the dorsal anterior cingulate cortex, the supplementary motor area, the anterior insula, the occipital gyrus and other frontal, temporal, parietal and cerebellar regions not captured in previous coordinate-based meta-analysis. We identified decreases in the BOLD signal during the anticipation of both social reward and punishment avoidance in regions of the default-mode network that were missed in individual studies likely due to a lack of power. Receipt of social rewards engaged a robust network of brain regions including the ventromedial frontal and orbitofrontal cortices, the anterior cingulate cortex, the amygdala, the hippocampus, the occipital cortex and the brainstem, but not the basal ganglia. Receipt of social punishments increased the BOLD signal in the orbitofrontal cortex, superior and inferior frontal gyri, lateral occipital cortex and the insula. In contrast to the receipt of social rewards, we also observed a decrease in the BOLD signal in the basal ganglia in response to the receipt of social punishments. Our results provide a better understanding of the brain circuitry involved in the processing of social rewards and punishment. Furthermore, they can inform hypotheses regarding brain areas where disruption in activity may be associated with dysfunctional social incentive processing during disease.

Ventilator associated pneumonia caused by Raoultella ornithinolytica in two immunocompetent trauma patients.

Infections with Raoultella ornithinolytica have recently been reported more frequently in the medical literature. This pathogen has the potential to cause many types of infections, including pneumonia. Here, we report the first two cases of ventilator-associated pneumonia (VAP) in trauma patients caused by Raoultella ornithinolytica. Both of these infections were successfully treated with antibiotics based on susceptibilities and the patients were able to be transferred out of the intensive care unit.

Taste processing: whetting our appetites.

Two G-protein-coupled receptors have been identified that are present in the apical membranes of rat and mouse taste cells and differentially distributed across the tongue and palate. They are strong candidates for being taste receptors and their discovery has provided new tools for research into gustatory processing.

Neural coding of gustatory information.

The nervous system encodes information relating chemical stimuli to taste perception, beginning with transduction mechanisms at the receptor and ending in the representation of stimulus attributes by the activity of neurons in the brain. Recent studies have rekindled the long-standing debate about whether taste information is coded by the pattern of activity across afferent neurons or by specifically tuned 'labeled lines'. Taste neurons are broadly tuned to stimuli representing different qualities and are also responsive to stimulus intensity and often to touch and temperature. Their responsiveness is also modulated by a number of physiological factors. In addition to representing stimulus quality and intensity, activity in taste neurons must code information about the hedonic value of gustatory stimuli. These considerations suggest that individual gustatory neurons contribute to the coding of more than one stimulus parameter, making the response of any one cell meaningful only in the context of the activity of its neighbors.

Distribution of gustatory sensitivities in rat taste cells: whole-cell responses to apical chemical stimulation.

Several taste transduction mechanisms have been demonstrated in mammals, but little is known about their distribution within and across receptor cells. We recorded whole-cell responses of 120 taste cells of the rat fungiform papillae and soft palate maintained within the intact epithelium in a modified Ussing chamber, which allowed us to flow tastants across the apical membrane while monitoring the activity of the cell with a patch pipette. Taste stimuli were: 0.1 m sucrose, KCl, and NH(4)Cl, 0.032 m NaCl, and 3.2 mm HCl and quinine hydrochloride (QHCl). When cells were held at their resting potentials, taste stimulation resulted in conductance changes; reversible currents >5 pA were considered reliable responses. Sucrose and QHCl produced a decrease in outward current and membrane conductance, whereas NaCl, KCl, NH(4)Cl, and HCl elicited inward currents accompanied by increased conductance. Combinations of responses to pairs of the four basic stimuli (sucrose, NaCl, HCl, and QHCl) across the 71-84 cells tested with each pair were predictable from the probabilities of responses to individual stimuli, indicating an independent distribution of sensitivities. Of 62 cells tested with all four basic stimuli, 59 responded to at least one of the stimuli; 16 of these (27.1%) responded to only one, 20 (33.9%) to two, 15 (25.4%) to three, and 8 (13.6%) to all of the basic stimuli. Cells with both inward (Na(+)) and outward (K(+)) voltage-activated currents were significantly more broadly tuned to gustatory stimuli than those with only inward currents.

Responsiveness of neurons in the hamster parabrachial nuclei to taste mixtures.

Responses from hamster parabrachial nuclei neurons to stimulation of the anterior tongue with sucrose, NaCl, HCl, quinine hydrochloride, and the six two-component mixtures of these stimuli were recorded. A cell's response to a mixture approached its response to the mixture's more effective component in the majority of cases, but was sometimes greater or smaller than this response. The best predictor of a neuron's response to a mixture, then, was its response to the mixture's more effective component. The single-component stimulus producing the maximum response was determined for each neuron and the response to this stimulus was compared with the responses evoked by the six mixtures. For 30% of the cells, a mixture elicited a response reliably, but only 1.1-2.1 times greater than the response to the best single-component stimulus. Thus, there were no neurons specialized to respond to these mixtures. The across-neuron patterns elicited by mixtures and the responses of best-stimulus classes to mixtures were studied for comparison with psychophysical data on taste mixtures. Mixtures were usually correlated with single-component stimuli in the mixture, but not with stimuli not in the mixture. In fact, five of the six mixtures fell directly between their components in a multidimensional scaling plot. In addition, a mixture was most effective in stimulating only those classes of neurons maximally stimulated by the mixture's components. These results correlate with psychophysical data suggesting that mixtures of taste stimuli evoke the same taste qualities as evoked by the mixture's components.

The organization of taste sensibilities in hamster chorda tympani nerve fibers.

Electrophysiological measurements of nerve impulse frequencies were used to explore the organization of taste sensibilities in single fibers of the hamster chorda tympani nerve. Moderately intense taste solutions that are either very similar or easily discriminated were applied to the anterior lingual surface. 40 response profiles or 13 stimulus activation patterns were considered variables and examined with multivariate statistical techniques. Three kinds of response profiles were seen in fibers that varied in their overall sensitivity to taste solutions. One profile (S) showed selectivity for sweeteners, a second (N) showed selectivity for sodium salts, and a third (H) showed sensitivity to salts, acids, and other compounds. Hierarchical cluster analysis indicated that profiles fell into discrete classes. Responses to many pairs of effective stimuli were covariant across profiles within a class, but some acidic stimuli had more idiosyncratic effects. Factor analysis of profiles identified two common factors, accounting for 77% of the variance. A unipolar factor was identified with the N profile, and a bipolar factor was identified with the S profile and its opposite, the H profile. Three stimulus activation patterns were elicited by taste solutions that varied in intensity of effect. Hierarchical cluster analysis indicated that the patterns fell into discrete classes. Factor analysis of patterns identified three common unipolar factors accounting for 82% of the variance. Eight stimuli (MgSO4, NH4Cl, KCl, citric acid, acetic acid, urea, quinine HCl, HCl) selectively activated fibers with H profiles, three stimuli (fructose, Na saccharin, sucrose) selectively activated fibers with S profiles, and two stimuli (NaNO3, NaCl) activated fibers with N profiles more strongly than fibers with H profiles. Stimuli that evoke different patterns taste distinct to hamsters. Stimuli that evoke the same pattern taste more similar. It was concluded that the hundreds of peripheral taste neurons that innervate the anterior tongue play one of three functional roles, providing information about one of three features that are shared by different chemical solutions.

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.

Postnatal development of palatal and laryngeal taste buds in the hamster.

Mammalian taste buds are distributed within several distinct subpopulations, innervated by branches of three cranial nerves. These taste bud populations originate and mature at different times in various mammalian species and are thought to play differential roles in the control of taste-mediated behaviors. The hamster is a common animal for the electrophysiological study of the gustatory system, and it has been shown that taste buds innervated by the IXth nerve develop postnatally in this species. To delineate further the development of the gustatory system of hamsters, we quantified the number of taste buds appearing on the palatal, nasopharyngeal, and laryngeal epithelium from birth through 120 days of age. Taste buds are present in almost adult numbers on the soft palate at birth, but only 39% of these are mature. Distinct taste pores, indicative of mature taste buds, increase in number until about 20-30 days of life, at which time all of the taste buds on the soft palate and on the nasoincisive papillae are fully developed. Taste buds are concentrated primarily on the posterior and medial portions of the soft palate. Taste buds located on the laryngeal surface of the epiglottis and the aryepiglottal folds are absent at birth and originate and mature over the following 120 days. Laryngeal taste buds are more concentrated on the aryepiglottal folds than on the epiglottis. On the soft palate and in the epiglottal region, the maturation of taste buds is well characterized by a logarithmic function (Y = a log X + B) relating the number of mature taste buds to postnatal age. On the soft palate, the length of the taste buds from base to apex correlates with the thickness of the epithelium, which increases with development. The diameter of mature taste buds on the soft palate does not change with age. In contrast to many mammalian species, in rodents taste bud development occurs mostly after birth. Rapid postnatal development progresses at a time when ingestive behavior is undergoing a number of significant changes. Taste buds in the larynx have been implicated in a number of laryngeal reflexes (i.e., apnea, swallowing) in several nonrodent species. The electrophysiological properties of superior laryngeal nerve fibers would suggest a similar function for epiglottal taste buds in the hamster.

Gustatory innervation in the rabbit: central distribution of sensory and motor components of the chorda tympani, glossopharyngeal, and superior laryngeal nerves.

Although rabbits have been used extensively in neurophysiological studies of the gustatory system, there is little information about the anatomical organization of taste in this species. Afferent and efferent central connections of three nerves innervating oral or laryngeal taste buds in the rabbit, including the chorda tympani (CT), the lingual-tonsillar branch of the glossopharyngeal (IX), and the superior laryngeal nerve (SLN), were traced by means of horseradish peroxidase neurohistochemistry. After entering the brainstem, most afferent fibers of CT, IX, and SLN turned caudally in the solitary tract, with fibers of the CT terminating in the nucleus of the solitary tract from 1.0 mm rostral to 3.8 mm caudal to the caudal border of the dorsal cochlear nucleus. There was terminal label from the CT also in the principal trigeminal nucleus. There was terminal label from the CT also in the principal trigeminal nucleus and the oral and intermediate divisions of the spinal trigeminal nucleus. Preganglionic parasympathetic cell bodies of the superior salivatory nucleus were labeled retrogradely in the reticular formation ventral to the rostral pole of the solitary nucleus. Afferent fibers of the IXth nerve terminated in the solitary nucleus from 0.6 mm rostral to 5.0 mm caudal to the caudal border of the dorsal cochlear nucleus. There were also labeled terminals in the principal trigeminal nucleus and in all three divisions of the spinal trigeminal nucleus. Cell bodies composing the inferior salivatory nucleus were labeled in and around the solitary nucleus and subadjacent reticular formation just rostral to the caudal border of the dorsal cochlear nucleus. There were also a few lightly labeled cells within the nucleus ambiguus at its most rostral extent. Afferent fibers of the SLN terminated in the solitary nucleus from 1.2 to 6.8 mm caudal to the dorsal cochlear nucleus. There was also some terminal label in the intermediate and caudal divisions of the spinal trigeminal nucleus. Many cells were retrogradely labeled in the nucleus ambiguus following application of HRP to the SLN and a few cells were labeled in and around the solitary nucleus just caudal to the dorsal cochlear nucleus. These three nerves show an overlapping rostral to caudal distribution of afferent input within the nucleus of the solitary tract that may be related to their gustatory and visceral functions.

Light and dark cells of rat vallate taste buds are morphologically distinct cell types.

Cells of mammalian taste buds have been classified into morphological types based on ultrastructural criteria, but investigators have disagreed as to whether these are distinct cell types or the extremes of a continuum. To address this issue, we examined taste buds from rat vallate papillae that had been sectioned transversely, rather than longitudinally, to their longest axis. In these transverse sections, dark (Type I) and light (Type II) cells were easily distinguished by their relative electron density, shape and topological relationships. Cells with electron-lucent cytoplasm (light cells) were circular or oval in outline, while those with electron-dense cytoplasm (dark cells) had an irregular outline with sheetlike cytoplasmic projections that separated adjacent light cells. A hierarchical cluster analysis of 314 cells across five morphological parameters (cell shape and area, and nuclear ellipticity, electron density and invagination) revealed two distinct groups of cells, which largely corresponded to the dark and light cells identified visually. These cells were not continuously distributed within a principal components factor solution. Differences in the means for dark and light cells were highly significant for each morphological parameter, but within either cell type, changes in one parameter correlated little with changes in any other. These analyses all failed to reveal cells with a consistent set of intermediate characteristics, suggesting that dark and light cells of rat vallate taste buds are distinct cell types rather than extremes of a continuum. Sections of taste buds were stained with antibodies to several carbohydrates, then observed by indirect immunofluorescence. Optical sections taken with a confocal laser-scanning microscope showed that the Lewis antigen was present only on spindle-shaped cells with circular or oval outlines and lacking transverse projections; these characteristic shapes matched those of light cells seen by electron microscopy. The H blood group antigen and the 2B8 epitope appeared at most cell-cell interfaces in the bud and are present on dark cells and possibly on some light cells. These findings relate molecular markers to morphological phenotypes and should facilitate future studies of taste cell turnover, development and regeneration.

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.

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.

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)

Differential expression of carbohydrate blood-group antigens on rat taste-bud cells: relation to the functional marker alpha-gustducin.

An afferent nerve fiber supplying a taste bud receives input from several taste receptor cells, yet is predominantly responsive to one of the classic taste qualities (salt, acid, sweet, or bitter). This specificity requires recognition between taste receptor cells and nerve fibers that may be mediated by surface markers correlating with function. In an effort to identify potential markers, we used immunofluorescence and confocal microscopy to examine expression of the oligosaccharide blood-group antigens Lewis(b), A, and H type 2 in taste buds of the rat oral cavity. We compared the distributions of these antigens with that of alpha-gustducin, a G-protein subunit implicated in responses to sweet- and bitter-tasting substances. The A and Lewis(b) antigens were present only on spindle-shaped cells whose apical processes reached the taste pore. These antigens were not present on epithelial cells surrounding taste buds, and Lewis(b) was not found elsewhere in the digestive tract. Lewis(b) and A were not removed by lipid extraction, suggesting that they are present on glycoproteins rather than glycolipids. All Lewis(b)-positive cells expressed alpha-gustducin, but only a fraction of alpha-gustducin-positive cells expressed Lewis(b). The fraction of taste-bud cells expressing Lewis(b) decreased in the order: vallate papillae > foliate papillae > nasoincisor duct. The epiglottis had almost no taste-bud cells that expressed Lewis(b). The A antigen appeared on taste-bud cells that also expressed alpha-gustducin in the order: foliate and vallate papillae > nasoincisor duct and epiglottis > fungiform papillae. In addition, the A antigen was present on many cells that lacked alpha-gustducin in foliate and vallate papillae. In vallate papillae, cells expressed either A or Lewis(b), but not both. Lewis(b) appears to be restricted to differentiated light cells that also express alpha-gustducin and may be involved in intercellular interactions of these cells.

Cellular expression of alpha-gustducin and the A blood group antigen in rat fungiform taste buds cross-reinnervated by the IXth nerve.

Although taste buds are trophically dependent on their innervation, cross-reinnervation experiments have shown that their gustatory sensitivities are determined by the local epithelium. Both the gustatory G-protein, alpha-gustducin, and the cell-surface carbohydrate, the A blood group antigen, are expressed by significantly fewer fungiform than vallate taste cells in the rat. In these experiments, one side of the anterior portion of the tongue was cross-reinnervated by the IXth nerve in order to determine whether the molecular expression of taste bud cells is determined by the epithelium from which they arise or by the nerve on which they are trophically dependent. The proximal portion of the IXth nerve was anastomosed to the distal portion of the chorda tympani (CT) nerve using fibrin glue (IX-CT rats). Control animals had the CT cut and reanastomosed using the same technique (CT-CT rats), or had the CT avulsed from the bulla and resected to prevent regeneration (CTX rats). The animals survived for 12 weeks postoperatively, and the tongues were removed, stained with methylene blue, and the fungiform taste pores counted on both sides. Tissue from the anterior 5 mm of the tongue was cut into 50-microm sections, which were incubated with antibodies against alpha-gustducin and the human blood group A antigen. In both CT-CT and IX-CT rats, there was regeneration of fungiform taste buds, although in both groups there were significantly fewer taste buds on the operated side of the tongue. The normal vallate papilla had a mean of 8.37 alpha-gustducin-expressing cells and 5.22 A-expressing cells per taste bud, whereas the fungiform papillae contained 3.06 and 0.23 cells per taste bud, respectively. In both CT-CT and IX-CT rats there was a normal number of cells expressing alpha-gustducin or the A antigen in regenerated taste buds; in the CTX animals there was a significant decrease in the expression of these markers. These results demonstrate that the molecular phenotype of taste bud cells is determined by the local epithelium from which they arise and not by properties of the innervating nerve.

Excitatory and inhibitory modulation of taste responses in the hamster brainstem.

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 recording in 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)-alpha-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 the N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate (APV) produces only a small effect. There are many gamma-aminobutyric acid (GABA)-containing neurons within the NST and taste-responsive NST cells are maintained under a tonic GABAergic inhibition. Microinjection of the GABAA receptor 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.

Substance P modulates taste responses in the nucleus of the solitary tract of the hamster.

The effects of substance (SP) microinjections on the electrophysiological response of gustatory neurons within the nucleus of the solitary tract (NST) were examined in hamsters following either anodal electrical or NaCl stimulation of the anterior tongue. For both types of stimulation, SP produced excitatory and suppressive effects on the activity of gustatory NST neurons, with excitatory effects being more common. In response to repetitive anodal stimulation of the tongue, the modulatory effect of SP lasted 30-400 s. In the presence of SP, the firing rate of 48% of the neurons was increased and that of 9% was decreased following NaCl stimulation. This dual action of SP could be due to direct excitation of teste-responsive neurons and to excitation of inhibitory local circuit neurons which, in turn, decrease the responsiveness of gustatory neurons.

Response properties of fibers in the hamster superior laryngeal nerve.

The purpose of the present investigation was to record electrophysiological responses from single fibers in the hamster superior laryngeal nerve (SLN) that were responsive to chemical stimulation of the larynx. Twenty chemical solutions, commonly used in studies of mammalian gustatory physiology, were applied to taste buds on and around the epiglottis. These stimuli were dissolved in physiological saline. Responses were the number of impulses elicited over a 15-s period following stimulus onset, above or below the background activity elicited by a previous rinse with saline. Unlike fibers in the hamster chorda tympani or glossopharyngeal nerves, SLN units were not easily classifiable into response types. Excitatory stimuli were primarily acids and bitter-tasting stimuli, with the order of their effectiveness being urea much greater than tartaric acid greater than HCl greater than KCl greater than citric acid greater than caffeine greater than quinine hydrochloride greater than acetic acid. The sweet-tasting stimuli and most salts other than KCl were primarily inhibitory, with the order of inhibitory effectiveness being CaCl2 greater than sucrose greater than fructose greater than LiCl greater than NaNO3 greater than Li2SO4 greater than NaCl. A hierarchical cluster analysis of fibers yielded no distinct clusters, yet differing sensitivities across the fibers were suggested. SLN fibers are highly responsive to sour and bitter stimuli, although they are not sensitive to fine differences in taste quality, as are fibers in other gustatory nerves.