In taste buds, the GPCR heterodimer TAS1R2 + TAS1R3 is considered the canonical taste receptor for sugars and noncaloric sweeteners. Nevertheless, evidence has accumulated for the presence of an alternative noncanonical transduction pathway that detects sugars, particularly at high concentration. Sodium-glucose transporter 1 (SGLT1) has been proposed as this transducer, selectively transporting glucose into a subset of taste bud cells which then transmit the signal to taste afferent neurons. To test for TAS1R-independent sweet taste detection, we conducted in vivo Ca2+ imaging on geniculate ganglion gustatory afferent neurons of Plcb2 knock-out (KO) mice of both sexes. These mice lack an essential signaling effector for TAS1R2 + TAS1R3, thus permitting visualizing signals for an alternative pathway. Indeed, glucose, sucrose, and other sugars evoked responses in Plcb2 KO gustatory afferent neurons but only when presented orally at 1 M. However, glucose, a known substrate for SGLT1, and fructose, not a substrate, elicited equivalent responses. Furthermore, response amplitudes for glucose and fructose were unaffected by varying Na+ concentration from 0 to 100 mM NaCl, again inconsistent with SGLT1. We also detected sugar-evoked responses in gustatory neurons from normal (heterozygous) mice that were consistent with a "noncanonical" pathway. Such responses were detected in separate neurons from those showing responses mediated by TAS1R2 + TAS1R3. Our results provide neural evidence for noncanonical taste transduction for many sugars but suggest that it may rely on mechanisms other than SGLT1. Most importantly, our data suggest that at least two separate, parallel neural pathways convey information on sweet taste detection from taste buds into the brainstem.

AbstractUmami is the meaty or savory taste elicited by monosodium glutamate and other amino acids. The presence of these amino acids in foods and beverages can alter dietary intake and nutritional balance and thus the health of human and nonhuman animals. Umami has been a major culinary influence in Eastern cultures for over a century and has gradually become an important factor in Western diets. Throughout its history, research on umami, especially the unique taste elicited by monosodium glutamate and its synergistic interaction with ribonucleotides such as inosine 5′-monophosphate, has played an important role in discovering peripheral taste receptors, cellular and molecular transduction mechanisms, and the neuroanatomy of the gustatory system. Umami taste has also been a focus of study to identify brain stem and cortical structures involved in sensory processing and generating food-directed behavior. This chapter provides a brief history of umami taste, a description of the molecular receptors and cellular transduction mechanisms for umami taste stimuli in chemosensory cells in the oral cavity and gut, and an overview of the brain systems involved in umami taste perception. An understanding of these aspects of umami taste is of fundamental importance for basic science and for healthcare professions working with patient populations with dietary challenges.

Taste information is encoded in the gustatory nervous system much as in other sensory systems, with notable exceptions. The concept of adequate stimulus is common to all sensory modalities, from somatosensory to auditory, visual, and so forth. That is, sensory cells normally respond only to one particular form of stimulation, the adequate stimulus, such as photons (photoreceptors in the visual system), odors (olfactory sensory neurons in the olfactory system), noxious heat (nociceptors in the somatosensory system), etc. Peripheral sensory receptors transduce the stimulus into membrane potential changes transmitted to the brain in the form of trains of action potentials. How information concerning different aspects of the stimulus such as quality, intensity, and duration are encoded in the trains of action potentials is hotly debated in the field of taste. At one extreme is the notion of labeled line/spatial coding - information for each different taste quality (sweet, salty, sour, etc.) is transmitted along a parallel but separate series of neurons (a "line") that project to focal clusters ("spaces") of neurons in the gustatory cortex. These clusters are distinct for each taste quality. Opposing this are concepts of population/combinatorial coding and temporal coding, where taste information is encrypted by groups of neurons (circuits) and patterns of impulses within these neuronal circuits. Key to population/combinatorial and temporal coding is that impulse activity in an individual neuron does not provide unambiguous information about the taste stimulus. Only populations of neurons and their impulse firing pattern yield that information.

In mammalian taste buds, Type I cells comprise half of all cells. These are termed “glial-like” based on morphologic and molecular features, but there are limited studies describing their function. We tested whether Type I cells sense chemosensory activation of adjacent chemosensory (i.e., Types II and III) taste bud cells, similar to synaptic glia. Using Gad2;;GCaMP3 mice of both sexes, we confirmed by immunostaining that, within taste buds, GCaMP expression is predominantly in Type I cells (with no Type II and ≈28% Type III cells expressing weakly). In dissociated taste buds, GCaMP+ Type I cells responded to bath-applied ATP (10-100 μm) but not to 5-HT (transmitters released by Type II or III cells, respectively). Type I cells also did not respond to taste stimuli (5 μm cycloheximide, 1 mm denatonium). In lingual slice preparations also, Type I cells responded to bath-applied ATP (10-100 μm). However, when taste buds in the slice were stimulated with bitter tastants (cycloheximide, denatonium, quinine), Type I cells responded robustly. Taste-evoked responses of Type I cells in the slice preparation were significantly reduced by desensitizing purinoceptors or by purinoceptor antagonists (suramin, PPADS), and were essentially eliminated by blocking synaptic ATP release (carbenoxolone) or degrading extracellular ATP (apyrase). Thus, taste-evoked release of afferent ATP from type II chemosensory cells, in addition to exciting gustatory afferent fibers, also activates glial-like Type I taste cells. We speculate that Type I cells sense chemosensory activation and that they participate in synaptic signaling, similarly to glial cells at CNS tripartite synapses. SIGNIFICANCE STATEMENT Most studies of taste buds view the chemosensitive excitable cells that express taste receptors as the sole mediators of taste detection and transmission to the CNS. Type I “glial-like” cells, with their ensheathing morphology, are mostly viewed as responsible for clearing neurotransmitters and as the “glue” holding the taste bud together. In the present study, we demonstrate that, when intact taste buds respond to their natural stimuli, Type I cells sense the activation of the chemosensory cells by detecting the afferent transmitter. Because Type I cells synthesize GABA, a known gliotransmitter, and cognate receptors are present on both presynaptic and postsynaptic elements, Type I cells may participate in GABAergic synaptic transmission in the manner of astrocytes at tripartite synapses.

In the simplest interpretation, ion channels mediate chemosensory transduction in salt taste, such as KC1: when present as a chemical stimulus, the salt merely distributes itself according to its electrochemical gradient through appropriate conductance channels that are open, thereby generating a receptor potential. Ion channels also participate in responses to other chemosensory stimuli, even to uncharged chemical stimulants such as sucrose. This chapter reviews the possible roles that ion channels may play in taste cells. Voltage-gated Na, Ca, and K channels all exist on taste cells. This was initially revealed by intracellular records of action potentials in amphibian taste cells; and has been substantiated with voltage-clamp recordings from amphibian and mammalian taste cells. Ionic channels other than K inevitably contribute to the leak resting membrane conductance, since the resting potential of taste cells is more depolarized than the equilibrium potential for K.

Chemical synapses between taste cells were first proposed based on electron microscopy of fish taste buds. Subsequently, researchers found considerable evidence for electrical coupling in fish, amphibian, and possibly mammalian taste buds. The development lingual slice and isolated cell preparations allowed detailed investigations of cell-cell interactions, both chemical and electrical, in taste buds. The identification of serotonin and ATP as taste neurotransmitters focused attention onto chemical synaptic interactions between taste cells and research on electrical coupling faded. Findings from Ca2+ imaging, electrophysiology, and molecular biology indicate that several neurotransmitters, including ATP, serotonin, GABA, acetylcholine, and norepinephrine, are secreted by taste cells and exert paracrine interactions in taste buds. Most work has been done on interactions between Type II and Type III taste cells. This brief review follows the trail of studies on cell-cell interactions in taste buds, from the initial ultrastructural observations to the most recent optogenetic manipulations.

Abstract Taste buds are the peripheral end organs of the gustatory system. Several thousand of these sensory organs are distributed throughout the oral cavity. Each taste bud consists of up to 100 cells that detect food chemicals and transmit this information to sensory afferent fibres that connect taste buds to the hindbrain. Individual taste buds detect many compounds, including those that elicit sweet, salty, bitter, sour, umami and perhaps other perceptions. There is no taste map on the tongue. Sensory receptor cells in taste buds transduce taste stimuli using G protein‐coupled taste receptors and ion channels. Gustatory stimulation causes the taste bud cells to secrete neurotransmitters, including ATP and serotonin, that excite sensory afferent fibres as well as mediate cell–cell (paracrine) interactions within a taste bud. Taste information travels from the hindbrain to cortical centres where the signals are integrated with olfaction to generate perception of flavours. Key Concepts Taste buds respond to chemical compounds found in foods and beverages. Taste buds consist of many cells that are dedicated to sensing multiple tastes, including sweet, sour, salty, bitter and umami. There is no taste map on the tongue. Taste cells comprise a renewing cell population with taste cells having lifespans of 8–12 days. There are 4 major types of cells in taste buds, each having a distinct function. Gustatory stimulation causes taste bud cells to secrete ATP and serotonin. Taste‐evoked ATP release is highly unusual: it is nonvesicular and involves secretion through large‐pore ion channels. Cells within a taste bud communicate with each other during taste stimulation via paracrine synaptic interactions. Gustatory signals transmitted to the brain cortex converge there with olfactory input to generate flavours.