Coding in the mammalian gustatory system

Abstract

To understand gustatory physiology and associated dysfunctions it is important to know how oral taste stimuli are encoded both in the periphery and in taste-related brain centres. The identification of distinct taste receptors, together with electrophysiological recordings and behavioral assessments in response to taste stimuli, suggest that information about distinct taste modalities (e.g. sweet versus bitter) are transmitted from the periphery to the brain via segregated pathways. By contrast, gustatory neurons throughout the brain are more broadly tuned, indicating that ensembles of neurons encode taste qualities. Recent evidence reviewed here suggests that the coding of gustatory stimuli is not immutable, but is dependant on a variety of factors including appetite-regulating molecules and associative learning.

Figure 1. Schematic representation of the rodent taste pathway organization

(a) Taste receptor cells (TRC) are the chemical sensors and are grouped in anatomical structures called taste buds distributed into different papillae of the tongue and the oral cavity. Each taste bud contains four different types of cells: 3 types of TRCs (types 1, 2 and 3) and basal cells involved in the genesis of new TRCs. (b) Three cranial nerves (VII, IX, X) innervate different parts of the oral cavity and convey taste information to the rNST. Input from the trigeminal nerve (V) also contributes to gustatory processing. The rNST is interconnected with other CNS regions. It receives input from the pontine parabrachial nucleus (PBN), the lateral hypothalamus, the gustatory cortex (GC), the central amygdala and reciprocally from the caudal (visceral) NST. The PBN projects to the VPMpc that in turn projects to the GC, that in turn projects to the OFC. OFC neurons project and receive inputs from the dorsolateral prefrontal cortex (not shown). The medial prefrontal cortex (not shown) appears to function as a sensory–visceromotor link that provides the major cortical output to visceromotor structures in the hypothalamus and brainstem. (c) Anatomical overview of the central taste pathways. Scale bar 1 mm in red boxes. Abbreviations: 4V: fourth ventricle, AI: agranular insular cortex, BA: basolateral amygdala, Bar: Barrington’s nucleus, DI: dysgranular insular cortex, GC: gustatory cortex, GI: granular insular cortex, Hyp: lateral hypothalamus, icp: inferior cerebellar peduncle, LA: lateral amygdala, LC: locus coeruleus, LPBV: lateral parabrachial nucleus ventral, M1: primary motor cortex, mcp: middle cerebellar peduncle, me5: mesencephalic 5 tract, Mo5: motor trigeminal nucleus, NST: nucleus of the solitary tract, OFC: orbitofrontal cortex, PBN: parabrachial nucleus, Pir: piriform cortex, S1: primary somatosensory cortex, S1bf: somatosensory cortex barrel field, S2: secondary somatosensory cortex, sol: solitary tract, sp5: spinal trigeminal tract, ts: tectospinal tract, VPL: ventral osterolateral nucleus of the thalamus, VPMpc: ventral posteromedial nucleus of the thalamus parvocellular division, vsc: ventral spinocerebellar tract.

Figure 2. Neural responses along the rodent taste pathway

(a) Five perceptually distinct taste qualities, umami, sweet, bitter, sour and salty (not shown but see [13]), are mediated by specific receptors and cells. The traces show whole nerve recordings of tastant-induced activity in the CT nerve of wild type and various gene-knockout (KO) mice or cell ablation studies (Pkd2l1-DTA). T1R1 (and T1R3) functions as a receptor for umami tastants, T1R2 (and T1R3) for sweet tastants, T2R5 for the bitter tastant cycloheximide and PKD2L1 for sour tastants. Pkd2l1-DTA refers to animals expressing diphtheria toxin in Pkd2l1 expressing TRCs cells. Red traces highlight specific taste deficits in each genetically altered mouse line. Adapted, with permission, from Ref [16]. (b) A single unit recording from the hamster chorda tympani (CT) nerve illustrating a neuron that was selectively responsive to super-threshold concentrations of both sweet tastants (sucrose and saccharin) but unresponsive to salty (NaCl), bitter (quinine) or sour (hydrochloric acid, HCl) tastants. Adapted, with permission, from Ref. [91]. (c) Proportional responses to sweet (0.3 M sucrose), salty (0.3 M NaCl), bitter (10 mM quinine) and sour (10 mM HCl) recorded from four different nerve cell types in the hamster gustatory system: CT nerve, greater superior petrosal nerve (GSP- from cranial nerve VII), glossopharyngeal nerve (GP, from CN IX) and from the superior laryngeal nerve (SLN, from CN X) fibres. Each pie represents the response to each stimulus as a proportion of the sum of the responses of that nerve to all stimuli. Adapted, with permission, from Ref [92]. (d) Single unit recording from individual neurons of the rat nucleus of solitary tract (NST) illustrating a broadly tuned neuron that responded to a variety of perceptually distinct tastants (ethanol, NaNO₃, KCl, HCl, MgCl₂ and citric acid) but apparently not to NaCl, sucrose or fructose. Adapted, with permission, from Ref. [50]. (e) Raster plots and peri-stimulus time histograms [PSTHs, which are the sum of the responses (action potentials) of individual trials for a given bin size aligned relatively to a stimulus onset] of a broadly tuned neuron from the rat gustatory cortex obtained while a rat was licking to receive a tastant at time 0 ms. Umami (MSG), salty (NaCl), sweet (sucrose) and bitter (quinine) tastants were delivered at two different concentrations for each. Other licks in which no tastants were delivered are indicated by inverted red triangles. Action potentials are indicated by dots. Although difficult to see at this scale, there are clear temporal differences in the responses to tastants. Adapted, with permission, from Ref. [73].

Figure 3. Topographical representations in the rat gustatory cortex

(a) Approximate size and location of the GC with respect to anatomical landmarks (blood vessels: middle cerebral artery, mca; rhv, rhinal veins) and other sensory areas of the brain (olfactory bulb, OB; primary somatosensory cortex barrel field, S1BF). (b) Schematic representation of the cortical territories activated following stimulation with four stimuli representing four different taste modalities (sweet, salty, bitter, sour). Same orientation as in (a). (c) Pleasant (sweet and salty) and unpleasant (bitter and sour) regions appear to be temporally distinguishable. Responses to pleasant stimuli seem to be represented more rostrally than responses to unpleasant stimuli. (d) Relationship between behavioural state and cortical state in the gustatory cortex. In a naïve (i.e. control) rat, cortical representations of the hedonically positive (saccharin, orange) and negative (quinine, gray) tastants are quite different, though commonly activated cortical territories exist. After conditioned taste aversive (CTA) training, in which the malaise inducing agent lithium chloride (LiCl) is paired with the ingestion of saccharin, the normally positive stimulus of the latter becomes aversive and the pattern changes accordingly to become more similar (highly correlative) to the quinine response. After saccharin aversion extinction (Glossary), the hedonic value of saccharin reverts to a positive response, and its cortical map is again less similar (low correlation) to the quinine pattern. Note that the new representation of saccharin after extinction may not be a simple return to the same one that existed prior to conditioning.

Figure 4. Sensory response is altered by satiety

(a) The responses of a neuron from the primate orbitofrontal cortex (OFC) that changes from being unselective between glucose and blackcurrant juice to becoming selective to blackcurrant juice as the subject ingested 50 mL of 20% glucose at each point. (b) Behavioural data of acceptance or rejection to the glucose on a rating scale ranging from +2 to −2. Adapted, with permission, from Ref. [86].