Learned aversions and taste qualities in hamsters

Interralations among taste perceptions in gloden hamsters (Mesocricetusauratus) were examined using generalizaions of learned tasteaversions. If stimulus A is avoided given a taste aversion hasbeen established to stimulus B, and vice versa, A and B ‘cross-generalize’.Stimuli within five groups cross-generalized. The groups ofcompounds were (i) sweeteners (fructose, saccharin, sucrose);(ii) sodium salts (NaCl, NaNO₃, Na₂SO₄): (iii) non-sodium salts(KCl, MgSO₄ NH₄Cl) plus quinine HCl; (iv) acids (acetic, hydrochloric,citric); and (v) urea. Only two pairs of stimuli from differentgroups cross-generalized (HCl—NH₄Cl. quinine HCl—urea).Neural patterns of response recorded form chorda tympam nervefibers in hamsters suggest that taste receptors on the anteriortongue distinguish among three groups of taste stimuli: sweeteners,sodium salts, and a group including non-sodium salts, acids,quinine HCl and urea. Neurons innervating other taste fieldsare likely to provide the information that hamsters use to discriminateamong the tastes of non-sodium-salt and non-sweetener stimuli.     

Behavioral discrimination between glutamate and the four basic taste substances in mice

1. Behavioural studies using the conditioned taste aversion (CTA) paradigm in mice showed that aversion conditioned to monosodium L-glutamate (MSG), which elicits a unique taste in humans, did not strongly generalize to any of the four basic taste stimuli, suggesting that mice could behaviourally discriminate between MSG and the four basic taste stimuli. 2. Denervation of bilateral glossopharyngeal nerve significantly increased behavioural similarities (the strength of generalization in the CTA paradigm) between MSG and sodium salts. This was not the case after destruction of the bilateral chorda tympani nerve. 3. These results suggest that taste information of glossopharyngeal nerve plays a more important role in the behavioural discrimination between MSG and the four basic tastes than does that of the chorda tympani nerve.     

Aldosterone increases gustatory neural response to NaCl in frog

1. The effect of aldosterone on frog gustatory response was investigated by recording integrated responses of the whole glossopharyngeal nerve elicited by taste stimuli. 2. After aldosterone (1 microM) was perfused to the basolateral side of taste cells through the lingual artery, the gustatory neural response for a NaCl stimulus was greatly enhanced, but the gustatory responses for CaCl2, hydrochloric acid, quinine hydrochloride and galactose were not affected. 3. At 3 and 6 hr after the onset of aldosterone perfusion, the magnitudes of the responses for NaCl increased to 2.0 and 3.6 times the control, respectively. 4. These results suggest that aldosterone may regulate the gustatory responses for monovalent salts alone.     

Iontophoretic application of bitter taste stimuli in hamsters

Recent electrophysiological studies on the iontophoretic applicationof taste stimuli by weak electric currents using rodents andfrogs have produced stimuli which appear to mimic the actionof salty, sour and sweet solutions. However, there has beenno report of an ionic stimulus which might serve as a bitteriontophoretic probe. Many common bitter stimuli are either uncharged(e.g. quinine, urea) or have mixed quality sensations (e.g.the bitter salts KCl, MgCl₂) and therefore are unsuitable. Thisreport investigates the use of four organic anions, all of whichare bitter to humans, which may serve as potential bitter stimulifor iontophoretic application to the tongue of the hamster whilerecording electrophysiologically from its chorda tympani nerve.These anions are m-nitrobenzene sulfonate (NBSA), picrate, cholateand m-nitrobenzoate (NBA). The electrophysiological responsesto cathodal polarization via these four anions plus saccharin,an effective cathodal stimulus in the hamster, form the sameefficacy series as chemical (i.e. normal sapid) presentationsof sodium salts of these anions, i.e. saccharin > NBSA >picrate > NBA > cholate. Behavioral evidence suggeststhat NBSA is sweet to hamsters while the latter three anions,picrate, NBA and cholate, are bitter. Electrophyiological observations,based on magnitude of response, appear to support these behavioralfindings. It was concluded that picrate, NBA and cholate mayserve as useful bitter stimulus probes for ionto-phoretic applicationin the hamster.     

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 mostpurely salty of all salts, but even this stimulus tastes sweetat low concentrations and somewhat sour at mid-range intensities.Other salts taste significantly sour or bitter in addition tosalty. Previous studies have shown that the saltiness of simplehalide salts is reduced by adaptation to NaCl, suggesting thata single mechanism might be responsible for the salty tasteof these stimuli. In electrophysiological studies in rodents,the response to NaCl is reduced by application to the tongueof the Na⁺- channel blocker amiloride. Organic Na⁺ salts aremore heavily dependent on this amiloride-sensitive transductioncomponent than NaCl, and are generally less salty and more sour.In order to investigate the relationship between NaCl saltinessand that evoked by other salts, we adapted the tongue to distilledH₂O and to 0.1 M NaCl and obtained direct magnitude estimatesof the taste intensity of 15 organic and inorganic Na⁺, Li⁺,K⁺ and Ca²⁺ salts, matched for total intensity. Subjects dividedthese magnitude estimates among the component taste qualities.Adaptation to NaCl abolished the taste of NaCl and LiCl, andeliminated the saltiness of all other salts. The magnitude estimatesof the bitterness and sourness of many salts increased afterNaCI adaptation. Since recent biophysical data suggest thatadaptation in taste receptors may involve whole-cell mechanisms,we propose that saltiness is reduced by NaCl adaptation becauseit originates in the subset of taste receptors responsive toNaCl. This implies that saltiness is coded within the CNS incells whose receptive fields include the NaCl-sensitive receptorcells and that the degree to which any salt tastes salty isdetermined by its ability to drive these receptors. This modelproposes, for example, that KCl has a salty component becauseit stimulates some of the same receptor cells as NaCl, eventhough the transduction mechanisms for KCl are different thanthose engaged by NaCl. Adaptation to NaCl blocks the saltinessof KCl and other salts because they stimulate NaCl-sensitivereceptor cells. Chem. Senses 20: 545–557, 1995.     

Taste judgments and gustatory stimulus duration: simple taste reaction times

Human simple taste reaction times to aqueous solutions of organicand inorganic molecules flowing across 39.3 mm² of the anterodorsaltongue were measured for stimulus durations of 50, 100, 300,1000 and 2000 ms. Median reaction times were >400 msand <850ms. Analyses of variance indicated that they differed acrossdurations for 2 mM Na-saccharin, 250 mM and 500 mM MgSO₄, 3.2mM HC1 and 214 mM monosodium glutamate. Pairwise comparisonsshowed significant differences between times to 50 or 100 msversus 2000 ms stimuli for these five solutions, but only forNa-saccharin and HC1 between 50 and 100 ms stimuli. Longer reactiontimes generally accompanied briefer durations. Simple tastereaction times did not differ across 50 ms through 2000 ms durationsfor 500 mM NaCl, 10 mM HCl or 2 mM Na-saccharin in 10 mM citricacid. A relationship between effective taste stimulus concentrationand sensitivity to stimulus duration is suggested. The lengthof taste reaction time, and the differences in reaction timebetween stimulus molecules, are attributed to central processingrather than receptor level events.     

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.     

Visual and Chemical Release of Feeding Behavior in Adult Rainbow Trout

Feeding behavior of adult rainbow trout (Oncorhynchus mykiss)is released by visual and/or chemical stimuli. Detection ofeither a conditioned visual or a conditioned chemical stimuluscreates an excitatory feeding state within the central nervoussystem which turns on feeding behavior composed of swimming,turning and biting/snapping actions. Particular amino acidsthat are highly effective physiological taste stimuli that arealso detected through olfaction (e.g. L-proline, L-alanine,L-leucine) release the initial sequence of food searching andbiting/snapping behaviors; however, an effective olfactory,but poor gustatory, stimulus (e.g. L-arginine) is rarely effectivebehaviorally. After bilateral removal of the paired olfactoryorgans, visual stimuli alone release the entire set of feedingbehavior patterns. Since amino acids that are highly potentphysiological taste stimuli do not release either feeding behavioror reflex biting/snapping actions in adult anosmic rainbow trout,it is postulated that the olfactory system detects potent tastestimuli and provides the afferent input for arousal and therelease of all feeding activity patterns. Chem. Senses 22: 375–382,1997.     

Asymmetrical neural cross-adaptation of hamster chorda tympani responses to sodium and chloride salts

Cross-adaptation has occurred when exposure to an adapting chemicalstimulus (A) reduces the response to a subsequent test stimulus(B). The degree of cross-adaptation between two stimuli is thoughtto reflect the overlap of their ‘neural activation processes’.We measured self- (A—A) and reciprocal crossadaptation(A—B, B—A) of the response of the hamster chordatympani nerve with lingual presentations of stimuli elicitingequal unadapted transient responses. Adapting and test stimuliwere 0.1 M NaCl, 0.1 M NaNO₃, 0.1 M NaBr, 0.4 M Na acetate (NaAc),0.09 M LiCl and 0.4 M NH₄Cl. Nearly complete and symmetricalcross-adaptation was seen for NaCl, NaNO₃ and NaBr. Those Nasalts paired with LiCl showed strong but asymmetrical cross-adaptation.Exposure to sodium completely eliminated the response to LiClbut not vice versa, suggesting that lithium and sodium are notcompletely interchangeable taste stimuli for the hamster chordatympani. Relatively little cross-adaptation between NH₄Cl andother salts suggested relatively separate neural activationprocesses. Strongly asymmetrical cross-adaptation was foundbetween NaAc and the other sodium salts. Responses to NaCl,NaNO₃ or NaBr were eliminated after adaptation to NaAc whereasthe response to NaAc during the reciprocal cross was strong.Asymmetries are discussed in reference to sensitivities of singlenerve fibers for the chorda tympani, effects of adaptation andthe concept of anion inhibition.     

Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction

Taste receptor cells (TRCs)respond to acid stimulation, initiating perception of sour taste.Paradoxically, the pH of weak acidic stimuli correlates poorly with theperception of their sourness. A fundamental issue surrounding sourtaste reception is the identity of the sour stimulus. We tested thehypothesis that acids induce sour taste perception by penetratingplasma membranes as H⁺ ions or as undissociated moleculesand decreasing the intracellular pH (pH_i) of TRCs. Our datasuggest that taste nerve responses to weak acids (acetic acid andCO₂) are independent of stimulus pH but strongly correlatewith the intracellular acidification of polarized TRCs. Taste nerveresponses to CO₂ were voltage sensitive and were blockedwith MK-417, a specific blocker of carbonic anhydrase. Strong acids(HCl) decrease pH_i in a subset of TRCs that contain apathway for H⁺ entry. Both the apical membrane and theparacellular shunt pathway restrict H⁺ entry such that alarge decrease in apical pH is translated into a relatively smallchange in TRC pH_i within the physiological range. Weconclude that a decrease in TRC pH_i is the proximate stimulus in rat sour taste transduction.

     

Ingestive responses to some heavy metal salts in mice and inhibition of taste nerve responses by metals

Preference-aversion for heavy metals in ddy mice was examinedusing the two-bottle preference technique. Mice preferred MnCl₂,CoCl₂ at certain concentration ranges, but avoided NiCl₂, CuCl₂,ZnCl₂ and CdCl₂. The avoidance threshold for the salts becamelower in the order of Mn > Co > Ni > Cd > Cu >Zn, though the degree of rejection for CuCl₂ was larger thanthat for ZnCl₂. Preferences for sucrose and Na saccharin werereduced by low concentrations of CuCl₂ or ZnCl₂. However, preferencefor glycine was scarcely affected by addition of either saltat 1 mM. Electrophysiological experiments in mice on the inhibitionby heavy metal salts of chords tympani nerve responses to thefour basic taste stimuli revealed that CuCl₂ and ZnCl₂ at 1mM inhibited the response to sucrose strongly and those to guinineHCl (QHCl) and NaCl moderately, but had no effect on the HClresponse. On the other hand, MnCl₂, CoCl₂ and NiCl₂ at 1 mMscarcely inhibited the response to sucrose but suppressed thoseto other stimuli. CoCl₂ moderately inhibited responses to allthe stimuli. In general, metal salts producing a larger inhibitionof neural responses to sucrose and QHCL are avoided by miceat a lower concentration.     

Aspects of compound-conditioning to gustatory stimuli in the housefly Musca domestica L.

Houseflies (Musca domestica L.) were trained in a compound-conditioning paradigm where the conditioning stimuli were water and 1% sodium chloride solution. The unconditioned stimulus was 16% sucrose solution. A high degree of conditioning was produced. Control experiments for pseudoconditioning and sensitization revealed that the response of the flies to the procedure were due to an associative process. Experiments with double-water conditioned stimuli and with an interval between stimulus presentations indicate that the marked response to the first conditioned stimulus may be due to stimulus generalization in which the water, rather than the salt component of both stimuli served as the learning cue.     

Decline of IXth nerve taste responses following nerve transection

Summated impulse discharges to taste solutions were recordedfrom intact and transected IXth nerves in the Mongolian gerbil(Meriones unguiculatus). Five taste stimuli were used: 0.3 MNH₄Cl, 0.3 M NaCl, 0.01 M HCl, 0.01 M quinine hydrochloride,and 0.5 M sucrose. 0.3 M NH₄Cl was the most effective stimulus.Taste responses from intact nerves were stable for more than10 hours. Following IXth nerve transection, the peak summatedresponse to 0.3 M NH₄Cl declined by 50% in a mean of 119 min.(Some animals failed to show this taste response decline inthe winter months.) The transected IXth nerve's spontaneousactivity and responses to other taste solutions also typicallydeclined. The continued presence of normal compound action potentialsindicated that the transection-induced decline in taste responsesdid not result from a failure of impulse propagation mechanismsin the nerve trunk. The results are consistent with the propositionthat transection interferes with axonal transport of materialsvital to the short-term maintenance of taste responses.     

The addition of CO2 to traditional taste solutions alters taste quality

Previous studies of the effect of carbonation on taste perception have suggested that it may be negligible, manifesting primarily in increases in the perceived intensity of weak salt and sour stimuli. Assuming CO2 solutions in the mouth stimulate only trigeminal nerve endings, this result is not altogether surprising; however, there are neurophysiological data indicating that CO2 stimulates gustatory as well as trigeminal fibers. In that case, carbonation might alter the quality profile of a stimulus without producing substantial changes in overall taste intensity--much as occurs when qualitatively different taste stimuli are mixed. To address this possibility, subjects were asked to rate the total taste intensity of moderate concentrations of stimuli representing each of the basic tastes and their binary combinations, with an without added carbonation. They then subdivided total taste intensity into the proportions of sweetness, saltiness, sourness, bitterness and 'other taste qualities' they perceived. The addition of carbonation produced only small increases in ratings of total taste intensity. However, rather dramatic alterations in the quality profiles of stimuli were observed, particularly for sweet and salty tastes. The nature of the interaction is consistent with a direct effect of carbonation/CO2 on the gustatory system, although the possibility that at least some of the observed effects reflect trigeminal-gustatory interactions cannot be ruled out.      

Molecular Signals into the Insular Cortex and Amygdala During Aversive Gustatory Memory Formation

In this paper, we will provide evidence of the putative molecular signals and biochemical events that mediate the formation of long-lasting gustatory memory trace. When an animal drinks a novel taste (the conditioned stimulus; CS) and it is later associated with malaise (unconditioned stimulus; US), the animal will reject it in the next presentation, developing a long-lasting taste aversion, i.e., the taste cue becomes an aversive signal, and this is referred to as conditioning taste aversion. Different evidence indicates that the novel stimulus (taste) induces a rapid and strong cortical acetylcholine activity that decreases when the stimulus becomes familiar after several presentations. Cholinergic activation via muscarinic receptors initiates a series of intracellular events leading to plastic changes that could be related to short- and/or long-term memory gustatory trace. Such plastic changes facilitate the incoming US signals carried out by, in part, the glutamate release induced by the US. Altogether, these events could produce the cellular changes related to the switch from safe to aversive taste memory trace. A proposed working model to explain the biochemical sequence of signals during taste memory formation will be discussed.     

PHYSICOCHEMICAL STUDIES OF TASTE RECEPTION VI: Interpretation of Anion Influences on Taste Response

Monolayers of lipids from bovine tongue epithelium were preparedas a model system for the gustatory receptor membrane to clarifythe effects of anions on the taste response. Changes in thesurface potential of the monolayers were measured by use ofthe ionizing-electrode method under the presence of sodium andcalcium salts carrying various species of anions in the aqueousphase. The organic and chaotropic anions showed the suppressiveeffect on the surface potentials as compared with Cl^–or NO₃^-. The influences of anion species on the surface potentialwere similar to those on the taste response recorded from glossopharyngealnerve of the frog. This suggested that the effects of anionson the taste response could be explained in terms of the electricalpotential at the interface between the receptor membrane andstimulating solution. Analysis of data on the surface potentialrevealed that a conformational change of the monolayers causedby non-electrical interaction between the monolayers and anionsis responsible for the suppressive effect.     

Inhibition of hamster chorda tympani neural response by copper chloride

Copper chloride was evaluated as a specific inhibitor of neuralresponses to sweet taste stimuli in the goldern hamster (Mesocricetusauratus). The chorda tympani whole-nerve response to taste stimuliwas recorded before and after the tongue was treated for 30s with 0.01, 0.1 and 1 mM CuCl₂. Sweet stimuli [sucrose, fructose,saccharin (calcium salt), D-phenylalanine], which primarilystimulate chorda tympani S fibers, and non-sweet stimuli (NaCl,NH₄Cl) were used. At 0.01 mM, copper chloride had little effect.At 0.10 mM it partially inhibited responses to sucrose and saccharin,but had little effect on responses to D-Phe, fructose, NaCl,NH₄Cl, or a mixture of sucrose plus L-Phe. L-Phe, which hasthe same chelating properties as D-Phe, is not an S-fiber stimulusand likely reduced sucrose inhibiton by chelating the cupricion.Analysis of concentration–response functions revealedthat 0.1 mM copper chloride inhibited the neural response tolow concentrations of sucrose by about 25%, but did not significantlyinhibit high concentrations of surcrose, suggesting competitiveinhibition. In contrast, 0.1 mM CuCl₂ reduced saccharin responsesby 25% throughtout the effective range, suggesting non-competitiveinhibition. Occupation of a saccharide receptor site by coppermay interfere with dimer but not monomer reception and distortthe saccharin receptor site. At 1 mM, CuCl₂ non-competitivelyinhibited responses to sucrose, fructose, saccharin and thenon-sweet NaCl (an N-fiber stimulus), but not NH₄Cl (an H-fiberstimulus). The mechanisms of copper chloride inhibition aredifficult to establish because its effects are weak at concentrationswhere they are specific.     

Gustatory neural response latencies in the frog

The major rate limiting steps in bullfrog peripheral nerve gustatoryresponse latencies were studied by measuring glossopharyngealnerve multi-unit activity, detecting response onset times, andcalculating rates of stimulus diffusion to receptor cells andsignal propagation along first order neurons. The stimulus deliverytechnique minimized physicochemical and mechanical artifacts,as well as neural responses to mechanical stimulation of thetongue. Neural activity was processed in 10 ms bins. Responseonsets were determined by a criterion that compared the statisticalprobability of the neural events during stimulus liquid presentationswith those during both Ringer's solution presentations afteradaptation to Ringer's and no-stimulus control conditions. Thiscriterion yielded response latencies of 70–110 ms for10 mM CaCl₂, 2 mM quinine hydrochloride, and 10^–5 M and10^–6 M cantharidin or Ringer's, and H₂O. No responsesoccurred during presentations of 10^–7 M cantharidin orRinger's after adaptation to Ringer's, or during the no-stimuluscontrol condition. From the measured latencies and calculatedrates of stimulus diffusion to receptor cells, and signal propagationalong first order neurons, we conclude that taste receptor cellevents and not perireceptor or signal propagatiog events arethe major rate limiting steps in gustatory response latencies.     

'Thermal taste' predicts higher responsiveness to chemical taste and flavor

Individual differences in taste perception have been explained in part by variations in peripheral innervation associated with the genetic ability to taste the bitter substances PTC and PROP. In the present study we report evidence of another source of individual differences that is independent of taste stimulus, taste quality, or gustatory nerve. Individuals who perceived taste from thermal stimulation alone (thermal taste) gave significantly higher taste ratings to chemical stimuli--often by a factor of >2:1--than did individuals who perceived no taste from thermal stimulation. This was true for all taste stimuli tested (sucrose, saccharin, sodium chloride, citric acid, quinine sulfate, MSG and PROP), for all three gustatory areas of the mouth (anterior tongue, posterior tongue and soft palate) and for whole-mouth stimulation. Moreover, the same individuals reported stronger sensations from the olfactory stimulus vanillin, particularly when it was sensed retronasally. The generality of the thermal-taster advantage and its extension to an olfactory stimulus suggests that it arises from individual differences in CNS processes that are involved in perception of both taste and flavor.     

Extensive Gustatory Cortex Lesions Significantly Impair Taste Sensitivity to KCl and Quinine but Not to Sucrose in Rats

Recently, we reported that large bilateral gustatory cortex (GC) lesions significantly impair taste sensitivity to salts in rats. Here we extended the tastants examined to include sucrose and quinine in rats with ibotenic acid-induced lesions in GC (GCX) and in sham-operated controls (SHAM). Presurgically, immediately after drinking NaCl, rats received a LiCl or saline injection (i.p.), but postsurgical tests indicated a weak conditioned taste aversion (CTA) even in controls. The rats were then trained and tested in gustometers to discriminate a tastant from water in a two-response operant taste detection task. Psychometric functions were derived for sucrose, KCl, and quinine. Our mapping system was used to determine placement, size, and symmetry of the lesions (~91% GC damage on average). For KCl, there was a significant rightward shift (ΔEC₅₀ = 0.57 log₁₀ units; p<0.001) in the GCX psychometric function relative to SHAM, replicating our prior work. There was also a significant lesion-induced impairment (ΔEC₅₀ = 0.41 log₁₀ units; p = 0.006) in quinine sensitivity. Surprisingly, taste sensitivity to sucrose was unaffected by the extensive lesions and was comparable between GCX and SHAM rats. The fact that such large bilateral GC lesions did not shift sucrose psychometric functions relative to SHAM, but did significantly compromise quinine and KCl sensitivity suggests that the neural circuits responsible for the detection of specific taste stimuli are partially dissociable. Lesion-induced impairments were observed in expression of a postsurgical CTA to a maltodextrin solution as assessed in a taste-oriented brief-access test, but were not reflected in a longer term 46-h two-bottle test. Thus, deficits observed in rats after extensive damage to the GC are also dependent on the test used to assess taste function. In conclusion, the degree to which the GC is necessary for the maintenance of normal taste detectability apparently depends on the chemical and/or perceptual features of the stimulus.