The coding of chemosensory quality (sweet, bitter, and a multiplicity of odor notes) is contrasted with the coding of spectral senses (pitch and color) in mammals. Taste and smell stimuli are detected directly by G protein-coupled receptors with discrete chemical ranges, whereas pitch and color stimuli are first partitioned by broadly tuned pigments and finely tuned localized mechano-detectors, respectively. Chemosensory qualities, determined by the taste and olfactory molecular receptors, are receptor cell-specific and are represented throughout the central nervous system (CNS). CNS inhibitory circuits likely promote mixture suppression and rapid stimulus adaptation, allowing consistent identification of a chemosensory stimulus superimposed on a complex and variable chemical environment.

Olfactory systems typically process signals produced by mixtures composed of very many natural odors, some that can be elicited by single compounds. The several hundred different olfactory receptors aided by several dozen different taste receptors are sufficient to define our complex chemosensory world. However, sensory processing by selective adaptation and mixture suppression leaves only a few perceptual components recognized at any time. Thresholds determined by stochastic processes are described by functions relating stimulus detection to concentration. Relative saliences of mixture components are established by relating component recognition to concentration in the presence of background components. Mathematically distinct stochastic models of perceptual component dominance in binary mixtures were developed that accommodate prediction of an appropriate range of probabilities from 0 to 1, and include errors in identifications. Prior short-term selective adaptation to some components allows temporally emergent recognition of non-adapted mixture-suppressed components. Thus, broadly tuned receptors are neutralized or suppressed by activation of other more efficacious receptors. This ‘combinatorial’ coding is more a process of subtraction than addition, with the more intense components dominating the perception. It is in this way that complex chemosensory mixtures are reduced to manageable numbers of odor notes and taste qualities.

Neurons in the rostral nucleus of the solitary tract (rNST) convey taste information to both local circuits and pathways destined for forebrain structures. This nucleus is more than a simple relay, however, because rNST neurons differ in response rates and tuning curves relative to primary afferent fibers. To systematically study the impact of convergence and inhibition on firing frequency and breadth of tuning (BOT) in rNST, we constructed a mathematical model of its two major cell types: projection neurons and inhibitory neurons. First, we fit a conductance-based neuronal model to data derived from whole cell patch-clamp recordings of inhibitory and noninhibitory neurons in a mouse expressing Venus under the control of the VGAT promoter. We then used in vivo chorda tympani (CT) taste responses as afferent input to modeled neurons and assessed how the degree and type of convergence influenced model cell output frequency and BOT for comparison with in vivo gustatory responses from the rNST. Finally, we assessed how presynaptic and postsynaptic inhibition impacted model cell output. The results of our simulations demonstrated 1) increasing numbers of convergent afferents (2-10) result in a proportional increase in best-stimulus firing frequency but only a modest increase in BOT, 2) convergence of afferent input selected from the same best-stimulus class of CT afferents produced a better fit to real data from the rNST compared with convergence of randomly selected afferent input, and 3) inhibition narrowed the BOT to more realistically model the in vivo rNST data. NEW & NOTEWORTHY Using a combination of in vivo and in vitro neurophysiology together with conductance-based modeling, we show how patterns of convergence and inhibition interact in the rostral (gustatory) solitary nucleus to maintain signal fidelity. Although increasing convergence led to a systematic increase in firing frequency, tuning specificity was maintained with a pattern of afferent inputs sharing the best-stimulus compared with random inputs. Tonic inhibition further enhanced response fidelity.

Chemosensory disorders, primarily olfactory, have diagnostic significance for prevalent human illnesses, but the multitude of smells makes measuring function appear daunting. The olfactory system operates under dynamic natural sensing conditions in which many individual odor chemicals are waxing and waning. Yet, in experimentally controlled simulations, mixture-component selective adaptation shows individual or shared prominent characteristic odors are detected but molecular stimulus features are not. As in other biological chemical signaling systems, including taste, odors activate dedicated receptors (OR). Given rapid OR adaptation with the passage of time, individual odor recognition is momentary. Receptive dendrites of the nearly 400 genetically variable human-OR in the olfactory epithelium critically project axons to the olfactory bulb through perforations in the cribriform plate of the skull. Analytic chemical-quality codes detect single odor-mixture components. However, identities of no more than 3 or 4 most salient odors are perceived due to central mixture-suppression, the mutual inhibition among diverse olfactory-bulb or cortical neurons. The componental codes allow olfaction to readily discern odor quality and valence of a wide range of unrelated chemicals, a few at a time. Head trauma may result in a partial or complete loss of smell and facial trauma a loss of taste-nerve function. Testing smell could plot the course of recovery from chronic traumatic encephalopathies that prevail in contact sports. Measuring brain function with olfaction would provide simpler and more direct monitoring of prognosis than biochemical sensors.

The intriguing observation that leptin decreases sweet-evoked peripheral gustatory responses has aroused much interest (Kawai K, Sugimoto K, Nakashima K, Miura H, Ninomiya Y. 2000. Leptin as a modulator of sweet taste sensitivities in mice. Proc Natl Acad Sci U S A. 97(20):11044-11049.) due to its implied importance in controlling appetite. The effects of this anorexic hormone, however, appear more conditional than originally believed. In this issue of Chemical Senses, a careful study by Glendinning and colleagues, find no effects of leptin on sweet-evoked chorda tympani responses, whereas an equally careful study by Meredith and colleagues, find decreased release of ATP and increased release of 5-HT from taste buds in response to sweet stimuli.

Studies of nicotine consumption in rodents often intend to investigate nicotine’s post-absorptive effects, yet little is known about the pre-absorptive sensory experience of nicotine drinking, including gustatory, trigeminal, and olfactory influences. We conditioned taste aversion (CTA) to nicotine in males of 3 inbred mouse strains: C57BL/6J, DBA/2J, and 129X1/SvJ by repeatedly pairing 150 μg/ml nicotine drinking with lithium chloride injections. Generalization to a variety of bitter, sour, sweet, salty, and irritant solutions and to nicotine odor was then examined. Nicotine CTA generalized to the bitter stimulus quinine hydrochloride and the chemosensory irritant spilanthol in all strains. It also showed strain specificity, generalizing to hydrogen peroxide (an activator of TRPA1) in C57BL/6J mice and to the olfactory cue of nicotine in DBA/2J mice. These behavioral assays demonstrate that the sensory properties of nicotine are complex and include multiple gustatory, irritant, and olfactory components. How these qualities combine at the level of perception remains to be assessed, but sensory factors clearly exert an important influence on nicotine ingestion and their contribution to net intake of nicotine should not be neglected in animal or human studies.

Component signaling in taste mixtures containing both beneficial and dangerous chemicals depends on peripheral processing. Unidirectional mixture suppression of chorda tympani (CT) nerve responses to sucrose by quinine and acid is documented for golden hamsters (Mesocricetus auratus). To investigate mixtures of NaCl and acids, we recorded multifiber responses to 50 mM NaCl, 1 and 3 mM citric acid and acetic acid, 250 μM citric acid, 20 mM acetic acid, and all binary combinations of each acid with NaCl (with and without 30 μM amiloride added). By blocking epithelial Na(+) channels, amiloride treatment separated amiloride-sensitive NaCl-specific responses from amiloride-insensitive electrolyte-generalist responses, which encompass all of the CT response to the acids as well as responses to NaCl. Like CT sucrose responses, the amiloride-sensitive NaCl responses were suppressed by as much as 50% by citric acid (P = 0.001). The amiloride-insensitive electrolyte-generalist responses to NaCl + acid mixtures approximated the sum of NaCl and acid component responses. Thus, although NaCl-specific responses to NaCl were weakened in NaCl-acid mixtures, electrolyte-generalist responses to acid and NaCl, which tastes KCl-like, were transmitted undiminished in intensity to the central nervous system. The 2 distinct CT pathways are consistent with known rodent behavioral discriminations.

Little is known about coding of taste mixtures in complex dynamic stimulus environments. A protocol developed for odor stimuli was used to test whether rapid selective adaptation extracted sugar and salt component tastes from mixtures as it did component odors. Seventeen human subjects identified taste components of "salt + sugar" mixtures. In 4 sessions, 16 adapt-test stimulus pairs were presented as atomized, 150-μL "taste puffs" to the tongue tip to simulate odor sniffs. Stimuli were NaCl, sucrose, "NaCl + sucrose," and water. The sugar was 98% identified but the suppressed salt 65% identified in unadapted mixtures of 2 concentrations of NaCl, 0.1 or 0.05 M, and sucrose at 3 times those concentrations, 0.3 or 0.15 M. Rapid selective adaptation decreased identification of sugar and salt preadapted ambient components to 35%, well below the 74% self-adapted level, despite variation in stimulus concentration and adapting time (<5 or >10 s). The 96% identification of sugar and salt extra mixture components was as certain as identification of single compounds. The results revealed that salt-sugar mixture suppression, dependent on relative mixture-component concentration, was mutual. Furthermore, like odors, stronger and recent tastes are emphasized in dynamic experimental conditions replicating natural situations.

Patchy variation in odor-evoked electrical activity in the human olfactory epithelium is found to correlate with stimulus pleasantness. This finding depends on a new technique for recording directly from awake humans.

Based on crosses among inbred strains derived principally from M. m. domesticus, sucrose octaacetate (SOA) aversion in laboratory mice has been thought for many years to be controlled by a single genetic locus (Soa) located on distal chromosome (Chr) 6. To expand knowledge of the genetic basis underlying SOA aversion, we have studied the M. m. molossinus derived strain (MSM) and MSM consomic strains on a M. m. domesticus (C57BL/6J: B6) host background. Using two-bottle preference procedures, MSM mice avoided 0.1 mM and 1 mM SOA while B6 mice were indifferent to 0.1 mM and exhibited slight aversion to 1 mM SOA. Preference tests of 16 available consomic strains implicated Chr 2, 4 and 15 in SOA aversion in addition to the prominent effect of the known Soa locus on Chr 6 (implicated by study of two congenic strains). The originally defined Soa locus is presumably associated with one or more members of the cluster of Tas2r genes on distal Chr 6 that code for bitter taste receptors. Our results point to the possible role of established Tas2r genes on Chr 2 and 15, as well as to genes not coding for bitter receptors (Chr 4), in SOA aversion. SOA aversion emerges from this consomic screen as being definitively under polygenic control. The genetic diversity captured by the MSM model system is shown to be a valuable tool to complement the limited genetic variation in the commonly used stocks derived from M m. domesticus.

Identification of odors of compounds introduced into changeable olfactory environments is the essence of olfactory coding, which focuses perception on the latest stimulus with the greatest salience. Effects of stimulus intensity and adapting time on mixture component identification after adapting with one component were each studied in 10 human subjects. Odors of 1 and 5 mM vanillin (vanilla) and phenethyl alcohol (rose) were identified, with adapting time varied by sniffing naturally once or twice, or sniffing 5 times, once every 2 s. Odors of water-adapted single compounds were identified nearly perfectly (94%), self-adapted to 51% but did not cross-adapt (94%), showing the 2 compounds had quickly adapting independent odors. Identifications of the vanilla and rose odors in water-adapted mixtures were reduced to 59% and 79%, respectively. Following single-component adaptation, the average 33% identification of odors of adapted (ambient) mixture components contrasted with the greater average 86% identification of new unadapted (extra) mixture components. Identifications were lower for 1 than 5 mM components when concentrations were not matched, and ambient component identifications were lower after 10-s adaptation than after 1 or 2 sniffs. Rapid selective adaptation and mixture component suppression manipulate effective intensity to promote emergence of characteristic odor qualities in dynamic natural settings.