From Channels to Behavior: An Integrative Model of NaCl Taste

Abstract

Though a fair amount is known about the transduction of individual tastants, there is scant evidence linking these specific transduction mechanisms with stimulus-evoked behavioral responses such as discrimination or rejection. The one exception to this involves the role of ASSCs in the transduction of sodium salts (and acids), which has been investigated in rats and hamsters at all levels along the gustatory pathway from receptor cell to behavior. The results of these various studies confirm that a significant portion of NaCl taste is mediated via an influx of sodium ions through ASSCs (references can be found in Lindemann 1996xLindemann, B. Physiol. Rev. 1996; 76: 719–766See all ReferencesLindemann 1996).Electrophysiological studies of the permeability properties of ASSCs in mammalian taste cells reveal that these channels are significantly permeable to Na+, Li+ and H+, have single channel conductances of ∼5 pS, and are blocked by submicromolar concentrations of amiloride. Based on these properties, it has become increasingly clear that the ASSCs in taste cells are similar molecularly and functionally to the heterooligomeric epithelial sodium channels (ENaCs) found in a variety of sodium-transporting epithelia. Recent RT–PCR and immunocytochemical studies confirm the presence of ENaC subunits in rat TRCs (e.g.Lindemann et al. 1998xLindemann, B, Barbry, P, Kretz, O, and Bock, R. Ann. N. Y. Acad. Sci. 1998; 855: 116–125Crossref | PubMedSee all ReferencesLindemann et al. 1998). Similar to their epithelial counterparts, the activity of ASSCs in TRCs is regulated by a number of natriferic hormones, hormones that control Na+ transport (Gilbertson 1998bxGilbertson, T.A. Ann. N. Y. Acad. Sci. 1998; 855: 860–868Crossref | PubMedSee all ReferencesGilbertson 1998b).Recent studies using amiloride to inhibit physiological and behavioral responses to sodium salts have provided a basis for a model of sodium salt taste linking the ASSC transduction mechanism to taste-guided behavior in mammals. Single gustatory nerve fibers and their primary target neurons in the NST are, as a rule, rather broadly responsive to stimuli of different taste qualities. However, a subset of individual fibers and neurons can be classified as “Na+-best” because they have a strong response to sodium and lithium salts relative to other stimuli. Others respond to sodium salts, but, importantly, they also respond well or better to nonsodium salts and acids. It was appreciated in early taste research that activity in different fiber types may contribute to a neural code for taste discrimination (Pfaffmann 1959xPfaffmann, C. Am. Psychol. 1959; 14: 226–232CrossrefSee all ReferencesPfaffmann 1959).The effects of lingual amiloride on taste responses in different neuron types of the NST, whose second-order gustatory neurons are a potential substrate for taste discrimination and other taste processes, have been studied in rats (Scott and Giza 1990xScott, T.R and Giza, B.K. Science. 1990; 249: 1585–1587Crossref | PubMedSee all ReferencesScott and Giza 1990) and hamsters (Boughter and Smith 1998xBoughter, J.D Jr. and Smith, D.V. J. Neurophysiol. 1998; 80: 1362–1372PubMedSee all ReferencesBoughter and Smith 1998). In both species, responses to NaCl in Na+-best neurons were significantly reduced or eliminated by micromolar concentrations of amiloride. Responses to NaCl in those cells broadly responsive to both salts and acids were completely unaffected. Although there is convergence of peripheral fibers onto gustatory neurons in the NST, input from different receptor mechanisms ultimately activates separate populations of neurons.In order to understand how the activity of afferent fibers and CNS neurons that are sensitive to amiloride may provide a basis for taste discrimination, Spector and colleagues tested the ability of amiloride to disrupt the discrimination between NaCl and KCl (Spector et al. 1996xSpector, A.C, Guagliardo, N.A, and St. John, S.J. J. Neurosci. 1996; 16: 8115–8122PubMedSee all ReferencesSpector et al. 1996). They conducted elegant behavioral experiments in the rat using an operant conditioning paradigm in which water-restricted rats were trained to discriminate between two different taste stimuli, NaCl and a nonsodium salt (KCl). Because there were both positive and negative consequences of each identification (i.e., presence or absence of water reward), the rats were more likely to report subtle differences between taste stimuli than in standard two-bottle preference tests. When the amiloride, which itself is tasteless to rats, was added to the salts, rats trained to distinguish between the two salts could no longer make the discrimination, performing at a level no better than chance. The effect of amiloride was significant at 10 μM, a concentration effective in receptor cell physiology experiments. The pattern of behavioral responses suggested that amiloride predominantly affected the taste quality of NaCl rather than KCl, which is consistent with electrophysiological observations that KCl does not elicit a strong response in the amiloride-sensitive Na+-best cells (Scott and Giza 1990xScott, T.R and Giza, B.K. Science. 1990; 249: 1585–1587Crossref | PubMedSee all ReferencesScott and Giza 1990). After amiloride treatment, the information contained in the neural pattern of activity is insufficient to discriminate sodium from a nonsodium salt. Despite the fact that the distribution of ASSC inputs to NST neurons is specific, the physiological data may, in fact, argue against a particular neuron type functioning as a “labeled line” for sodium salts. Na+-best neurons respond to multiple stimuli, and both NaCl and acid responses were blocked by amiloride in these cells in the hamster NST (Boughter and Smith 1998xBoughter, J.D Jr. and Smith, D.V. J. Neurophysiol. 1998; 80: 1362–1372PubMedSee all ReferencesBoughter and Smith 1998). This organization suggests that any one neuron type alone or any one transduction mechanism alone may be insufficient for the discrimination among different-tasting stimuli.As more taste transduction mechanisms are elucidated, it will be necessary to attempt to link the effects of tastants at the receptor cell level with, ultimately, the behavior of the organism. For example, bitter taste in humans is stimulated by a diverse array of compounds, ranging from simple salts to toxic plant alkaloids. Multiple transduction mechanisms for bitter stimuli have been proposed (e.g.Gilbertson 1998axGilbertson, T.A. Front. Oral Biol. 1998; 9: 1–28CrossrefSee all ReferencesGilbertson 1998a). But behavioral studies with rodents indicate that while many of these compounds provoke an avoidance response, others do not. To understand how the mammalian CNS encodes bitter and other taste qualities will require the integration of research at the receptor cell, afferent nerve fiber, central taste nuclei, and behavioral levels.‡To whom correspondence should be addressed (e-mail: tim.gilbertson@tasteful.com).