Pontine gustatory activity is altered by electrical stimulation in the central nucleus of the amygdala.

Visceral signals and experience modulate the responses of brain stem neurons to gustatory stimuli. Both behavioral and anatomical evidence suggests that this modulation may involve descending input from the forebrain. The present study investigates the centrifugal control of gustatory neural activity in the parabrachial nucleus (PBN). Extracellular responses were recorded from 51 single PBN neurons during application of sucrose, NaCl, NaCl mixed with amiloride, citric acid, and QHCl with or without concurrent electrical stimulation in the ipsilateral central nucleus of the amygdala (CeA). Based on the sapid stimulus that evoked the greatest discharge, 3 neurons were classified as sucrose-best, 32 as NaCl-best, and 16 as citric acid-best. In most of the neurons sampled, response rates to an effective stimulus were either inhibited or unchanged during electrical stimulation of the CeA. Stimulation in the CeA was without effect in two sucrose-best neurons, nine NaCl-best neurons, and one citric acid-best neuron. Suppression was evident in 1 sucrose-best neuron, 18 NaCl-best neurons, and 15 citric acid-best neurons. In NaCl-best neurons inhibited by CeA stimulation, the magnitude of the effect was similar for spontaneous activity and responses to the five taste stimuli. Nonetheless, the inhibitory modulation of gustatory sensitivity increased the relative effectiveness of NaCl resulting in narrower chemical selectivity. For citric acid-best neurons, the magnitude of inhibition produced by CeA activation increased with an increase in stimulus effectiveness. The responses to citric acid were inhibited significantly more than the responses to all other stimuli with the exception of NaCl mixed with amiloride. The overall effect was to change these CA-best neurons to CA/NaCl-best neurons. In a smaller subset of NaCl-best neurons (n = 5), CeA stimulation augmented the responsiveness to NaCl but was without effect on the other stimuli or on baseline activity. It appears that electrical stimulation in the CeA modulates response intensity, as well as the type of gustatory information that is transmitted in a subset of NaCl-best neurons. These findings provide an additional link between the amygdala and the PBN in the control of NaCl intake, modulating the response and the chemical selectivity of an amiloride-sensitive Na+ detecting input pathway.

Gustatory neuron types in the periphery: a functional perspective.

Robert P. Erickson's research and writings formed the intellectual backdrop and guiding force for much of the major research on sensory coding in taste. As articulated best by Erickson, consideration focused on the relative merits of labeled-line and across-fiber pattern theory. The present article focuses primarily on a review of the electrophysiological and behavioral studies on salt taste and salt taste-mediated behavior in rodents. The evidence clearly shows that the peripheral gustatory system consists of a few neuron types/groups with well-defined physiological response characteristics. Electrophysiological studies of the chorda tympani nerve define a physiological group of narrowly tuned neurons selectively responsive to NaCl stimuli. It appears that this is a sodium-sensing module that functions primarily in the detection, recognition, and ingestion of NaCl.

Gustatory neuron types in rat geniculate ganglion.

We used extracellular single-cell recording procedures to characterize the chemical and thermal sensitivity of the rat geniculate ganglion to lingual stimulation, and to examine the effects of specific ion transport antagonists on salt transduction mechanisms. Hierarchical cluster analysis of the responses from 73 single neurons to 3 salts (0.075 and 0.3 M NaCl, KCl, and NH(4) Cl), 0.5 M sucrose, 0.01 M HCl, and 0.02 M quinine HCl (QHCl) indicated 3 main groups that responded best to either sucrose, HCl, or NaCl. Eight narrowly tuned neurons were deemed sucrose-specialists and 33 broadly tuned neurons as HCl-generalists. The NaCl group contained three identifiable subclusters: 18 NaCl-specialists, 11 NaCl-generalists, and 3 QHCl-generalists. Sucrose- and NaCl-specialists responded specifically to sucrose and NaCl, respectively. All generalist neurons responded to salt, acid, and alkaloid stimuli to varying degree and order depending on neuron type. Response order was NaCl > HCl = QHCl > sucrose in NaCl-generalists, HCl > NaCl > QHCl > sucrose in HCl-generalists, and QHCl = NaCl = HCl > sucrose in QHCl-generalists. NaCl-specialists responded robustly to low and high NaCl concentrations, but weakly, if at all, to high KCl and NH(4) Cl concentrations after prolonged stimulation. HCl-generalist neurons responded to all three salts, but at twice the rate to NH(4) Cl than to NaCl and KCl. NaCl- and QHCl-generalists responded equally to the three salts. Amiloride and 5-(N,N-dimethyl)-amiloride (DMA), antagonists of Na(+) channels and Na(+)/H(+) exchangers, respectively, inhibited the responses to 0.075 M NaCl only in NaCl-specialist neurons. The K(+) channel antagonist, 4-aminopyridine (4-AP), was without a suppressive effect on salt responses, but, when applied alone in solution, it evoked a response in many HCl-generalists and one QHCl-generalist neuron so tested. Of the 39 neurons tested for their sensitivity to temperature, 23 responded to cooling and chemical stimulation, and 20 of these neurons were HCl-generalists. Moreover, the responses to the four standard stimuli were reduced progressively at lower temperatures in HCl- and QHCl-generalist neurons, but not in NaCl-specialists. Thus sodium channels and Na(+)/H(+) exchangers appear to be expressed exclusively on the membranes of receptor cells that synapse with NaCl-specialist neurons. In addition, cooling sensitivity and taste-temperature interactions appear to be prominent features of broadly tuned neuron groups, particularly HCl-generalists. Taken all together, it appears that lingual taste cells make specific connections with afferent fibers that allow gustatory stimuli to be parceled into different input pathways. In general, these neurons are organized physiologically into specialist and generalist types. The sucrose- and NaCl-specialists alone can provide sufficient information to distinguish sucrose and NaCl from other stimuli, respectively.

Potential mechanisms for functional changes in taste receptor cells following sodium deficiency in mammals.

Sodium is an essential nutrient for life, and its level in the body is tightly regulated. When sodium deficient, some mammals alter their behavior towards salt by avidly consuming it, even at concentrations animals typically choose to avoid. This change in acceptance is accompanied by a reduction in the response of the gustatory chorda tympani nerve to sodium solutions. More specifically, the response rate of the sodium-specialist units to NaCl stimulation is reduced following sodium deficiency or adrenalectomy. The initial transduction of the chemical signal is mediated, in part, by Na+ influx through epithelial Na+ channels in the apical membrane of taste cells that synapse with the specialist neurons. Circulating hormones like angiotensin II and adrenocorticotropin hormone, which are released in response to sodium deficiency and adrenalectomy, could regulate the activity of Na+ channels through G-protein linked second-messenger systems. These putative pathways are of interest because they have been described in mammalian taste receptor cells. The present review will summarize evidence linking some hormones of fluid homeostasis with the apparent attenuation of input from sodium-specialist neurons.

Temperature and amiloride alter taste nerve responses to Na+, K+, and NH+4 salts in rats.

The effects of adaptation/stimulus temperature (25 degrees C vs. 35 degrees C) on taste nerve responses to salt stimulation and amiloride suppression were assessed in rats. We measured the integrated responses of the chorda tympani nerve to 500 mM concentrations of NaCl, Na2SO4, sodium acetate (NaAc), KCl, K2SO4, potassium acetate (KAc), NH4Cl, (NH4)2SO4, and ammonium acetate (NH4Ac) mixed with or without 100 microM amiloride hydrochloride at 35 degrees C. Taste nerve responses to all Na+ and NH4+ salts, but not K/ salts, were significantly smaller at 25 degrees C than at 35 degrees C. Amiloride significantly suppressed taste nerve responses to all salts (Na+ salts > K+ salts > NH4+ salts); amiloride suppression of Na+ and NH4+ salts was significantly greater at 25 degrees C than at 35 degrees C. Benzamil-HCl, a more potent Na+ channel blocker compared to amiloride, strongly suppressed taste nerve responses to NaCl and KCl, but not to NH4Cl. Amiloride and benzamil suppression of NaCl responses were similar; however, amiloride suppressed KCl responses more than did benzamil. The results suggest that: (1) amiloride-sensitive Na+ channels are involved to varying degrees in the transduction of sodium and potassium salt taste, and (2) amiloride may inhibit membrane proteins other than passive Na+ channels during stimulation with potassium and ammonium salts.

Role for epithelial Na+ channels and putative Na+/H+ exchangers in salt taste transduction in rats.

The effects of the epithelial Na+ channel antagonists amiloride and benzamil and the Na+/H+ exchange antagonist 5-(N,N-dimethyl)-amiloride (DMA)-Cl on the integrated responses of the chorda tympani nerve to 30, 75, 150, 300, and 500 mM concentrations of NaCl, KCl, and NH4Cl were assessed in male Sprague-Dawley rats. Based on evidence from other systems, 1 and 25 microM amiloride and benzamil were chosen to selectively inhibit epithelial Na+ channels and 1 microM DMA was chosen to selectively inhibit Na+/H+ exchange. When added to stimulating salt solutions, amiloride, benzamil, and DMA were each effective in inhibiting responses to all three salts. The degree of inhibition varied with drug, salt, and salt concentration, but not drug dose. Amiloride suppressed NaCl responses to a greater degree than KCl and NH4Cl responses, whereas DMA suppressed NH4Cl responses to a greater degree than NaCl and KCl responses. In all but one case (25 microM amiloride added to KCl), drug suppression of taste nerve responses decreased with an increase in salt concentration. The present results suggest that 1) epithelial Na+ channels in rat taste receptor cells may play a role in KCl and NH4Cl taste transduction; 2) a Na+/H+ exchange protein may be present in taste receptor cells, representing a putative component, in addition to epithelial Na+ channels, in salt taste transduction; and 3) salt taste detection and transduction may depend on the utilization of a combination of common and distinct transcellular pathways.

Amiloride inhibits taste nerve responses to NaCl and KCl in Sprague-Dawley and Fischer 344 rats.

In a two-bottle test, Sprague-Dawley rats preferentially consume a greater amount of hypotonic and isotonic NaCl solutions relative to water, whereas inbred Fischer 344 (F344) rats fail to prefer NaCl solutions at any concentration relative to water. To determine whether taste contributes to this strain difference, we measured the integrated neural responses of the chorda tympani nerve to a concentration range of NaCl and KCl solutions. The amiloride-sensitive component of the taste nerve response was assessed by adding amiloride during salt stimulation in Experiment 1, and by pretreating the taste receptors with amiloride prior to salt stimulation in Experiment 2. Adding amiloride to NaCl during sustained neural activity suppressed chorda tympani nerve responses more than pretreating the tongue with amiloride. Adding amiloride during salt stimulation also partially suppressed chorda tympani neuron responses to KCl, a presumed control stimulus. The neural responses of the chorda tympani nerve to NaCl and KCl were similar for salt-avoiding F344 and salt-preferring Sprague-Dawley rats. However, amiloride pretreatment suppressed the taste nerve responses to NaCl significantly less in F344 rats than in Sprague-Dawley rats. The strain difference in the amiloride-sensitive component of the taste response may contribute to the difference in NaCl preference.

Tongue adaptation temperature influences lingual nerve responses to thermal and menthol stimulation.

Menthol, a tangible substance present in many orally administered products, can produce a powerful influence on the perceived intensity of subsequent thermal stimulation in humans as well as the response magnitudes of thermally sensitive neurons in rats. However, there are no prior studies examining the influence of adaptation temperature on perceived intensity and/or response magnitudes of thermally sensitive neurons to subsequent menthol stimulation. We identified 32 thermally sensitive neurons that increased their discharge rate to a gradual temperature decrement beginning from 35 degrees C and dropping to 10 degrees C at 1 degree C/s. Based on their response threshold, time-to-peak, and range of sensitivity, these thermally sensitive lingual neurons were found to be divisible into two distinct groups. Group 1 neurons (n = 21) responded best to the upper cool range (34-15 degrees C) of the temperature decrement, whereas Group 2 neurons (n = 11) responded to the lower cold range (32-10 degrees C) of the temperature decrement. Our Group 1 and Group 2 neurons may be analogous to low threshold and high threshold cold receptors identified previously in primates. We also examined the responses of lingual neurons to 0%, 25%, 50% and 75% dilution's of a stock menthol concentration (1.28 mM) at 25 and 35 degrees C adaptation temperatures. Menthol responses across all concentrations were far larger after adaptation to 35 degrees C compared to 25 degrees C. Furthermore, only during 35 degrees C adaptation did responses to menthol stimulation persist during the ensuing 20 s after menthol off-set and water on-set.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural responses of thermal-sensitive lingual fibers to brief menthol stimulation.

The addition of the coolant menthol to several oral and facial products is to increase their attractiveness and commercial value. Little is, however, known about the physiological basis of menthol's sensory effects. We studied the electrophysiological responses of 45 thermal-sensitive lingual fibers to anterior tongue stimulation (10 s) with menthol in male Sprague-Dawley rats. Menthol responses were unlike the responses to cold water. Cold water (6 degrees C, 15 degrees C) elicited an immediate sustained increase in impulse frequencies of thermal-sensitive fibers adapted to room temperature water (22-24 degrees C). Inhibitory off-responses followed cold water stimulation. Depending on the concentration and time of measurement, menthol stimulation either excited, inhibited, or had no effect on impulse frequencies of thermal-sensitive fibers. Strong menthol (0.64 mM, 1.28 mM) unequivocally excited thermal-sensitive fibers with a response latency of 4-6 s. In most cases after menthol stimulation, the impulse frequencies returned to baseline; there were no off-responses. Weak menthol (0.0128 mM, 0.064 mM, 0.128 mM) inhibited impulse frequencies of 14 thermal-sensitive fibers and excited impulse frequencies of 6 fibers primarily during the first 2 s of stimulation. Menthol responses were also unlike responses to stimulation with taste solutions. Most taste solutions (30 and 100 mM NaCl, 0.3 and 1 mM quinine-HCl, 0.3 mM citric acid) significantly inhibited impulse frequencies but only during the first 2-5 s of stimulation. The effect of NaCl was biphasic with the initial inhibitory phase followed by an excitatory phase during the second 5 s of stimulation. An excitatory off-response followed quinine stimulation. While considered principally a coolant, menthol elicits a unique pattern of responses from trigeminal and taste nerve endings quite unlike those of conventional thermal and taste stimuli.

Taste prestimulation increases the chorda tympani nerve response to menthol.

Electrophysiological recordings of the summated response of the chorda tympani nerve to menthol stimulation of the tongue were obtained from 15 adult Sprague-Dawley rats. The chorda tympani nerve response to menthol was of short duration, ending within 2.5 s after stimulus onset, leaving the receptors in a state of insensitivity to subsequent menthol stimulation. Rinse durations with deionized-distilled water up to 10 min failed to bring the receptors back to their original prestimulus state. Although stimulation with menthol prevented taste receptors from responding to subsequent presentations of menthol, the chorda tympani nerve would respond normally to NaCl, NH4Cl, KCl, sodium acetate, glucose, citric acid, and quinine-HCl solutions. Prior stimulation with one of these taste solutions resulted in the recovery of the menthol response. The magnitude of the recovered menthol response depended on the magnitude of the phasic response elicited by the preceding taste stimulus. A general explanation involving possible reception and transduction mechanisms was offered to account for menthol's unexpected stimulatory effects on the chorda tympani nerve.