Taste System Valence and Identity

 

Nature, volume 558, pages127–131 (2018)

The coding of valence and identity in the mammalian taste system

Wang, Sarah Gillis-Smith, et.al.

Howard Hughes Medical Institute, Columbia University, New York, NY, USA

Department of Biochemistry and Molecular Biophysics, Columbia College of Physicians and Surgeons, Columbia University, New York, NY, USA

Department of Neuroscience, Columbia College of Physicians and Surgeons, Columbia University, New York, NY, USA

Department of Psychiatry and New York State Psychiatric Institute, Columbia University, New York, NY, USA

National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA

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The ability of the taste system to identify a tastant (what it tastes like) enables animals to recognize and discriminate between the different basic taste qualities. The valence of a tastant (whether it is appetitive or aversive) specifies its hedonic value and elicits the execution of selective behaviours. Here we examine how sweet and bitter are afforded valence versus identity in mice. We show that neurons in the sweet-responsive and bitter-responsive cortex project to topographically distinct areas of the amygdala, with strong segregation of neural projections conveying appetitive versus aversive taste signals. By manipulating selective taste inputs to the amygdala, we show that it is possible to impose positive or negative valence on a neutral water stimulus, and even to reverse the hedonic value of a sweet or bitter tastant. Remarkably, mice with silenced neurons in the amygdala no longer exhibit behaviour that reflects the valence associated with direct stimulation of the taste cortex, or with delivery of sweet and bitter chemicals. Nonetheless, these mice can still identify and discriminate between tastants, just as wild-type controls do. These results help to explain how the taste system generates stereotypic and predetermined attractive and aversive taste behaviours, and support the existence of distinct neural substrates for the discrimination of taste identity and the assignment of valence.

The taste system is responsible for detecting and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Each of these five tastes is detected by specialized taste receptor cells on the tongue and palate epithelium, with different taste receptor cells dedicated to each of the taste modalities. In rodents, taste information travels from taste receptor cells in the oral cavity to primary gustatory cortex (insular cortex) via four neural stations: taste receptor cells to taste ganglia, then to the nucleus of the solitary tract, the parabrachial nucleus, the thalamus and to insular cortex. Intrinsic and two-photon imaging studies have shown that sweet and bitter taste are represented in the cortex in topographically separate cortical fields; by optogenetically activating these taste cortical fields in awake mice, it is possible to evoke prototypical taste behaviours in the total absence of taste stimuli.

The two most important sensory features of a taste stimulus are its identity and its valence. We hypothesized that by examining the neural targets of the sweet and bitter cortical fields it may be possible to uncover the circuit logic for appetitive versus aversive tastes. To trace the projections of neurons in the sweet and bitter cortex, we labelled neurons in the sweet cortical field with enhanced green-fluorescent protein (eGFP), those in the bitter cortex with red-fluorescent protein (tdTomato), and then the whole brains were examined by clearing and rapid 3D imaging with light-sheet microscopy using clear, unobstructed brain imaging and computational analysis (CUBIC). Our results show that projections from the sweet and bitter cortical fields target multiple brain areas, including contralateral taste cortex, amygdala, entorhinal cortex, caudoputamen and thalamus. Notably, sweet and bitter cortical projections exhibited strong segregation as separate lines while navigating to the amygdala, with neurons from the sweet cortical field terminating in the anterior basolateral amygdala (BLA), whereas neurons from the bitter cortical field predominantly projected to central amygdala (CEA), with some terminals in the posterior BLA. We extended these findings by performing anterograde labelling experiments using adeno-associated virus (AAV)-based transsynaptic transfer of Cre-recombinase9 from sweet and bitter cortex to targets in the amygdala. These results substantiated that the BLA was the target of sweet cortex projections, and the CEA was the target of bitter cortex projections.

The amygdala is a key brain structure involved in processing emotions, motivation and positive and negative stimuli. Previous studies have shown that the BLA and CEA both contain distinct populations of neurons that are activated by negative or positive stimuli. Our finding of such strong segregation of appetitive (sweet) versus aversive (bitter) projections to the amygdala immediately suggests an anatomical division for the generation of valence-specific behavioural responses to tastants.

 

If the amygdala imposes valence on tastants (that is, it represents the hedonic value of a tastant to drive valence-specific behaviours), then optogenetic activation of the terminals of sweet cortical neurons in the BLA should elicit attractive responses, whereas activation of bitter projections should evoke aversive behaviours. Therefore, we generated mice expressing channelrhodopsin-2 (ChR2) in either the sweet or bitter cortical field, implanted optical fibres over the amygdala, and used a place-preference test to measure responses to photostimulation of the cortico-amygdalar projections. Our results showed that mice avoided the chamber linked to photostimulation of the bitter cortico-amygdalar projections but exhibited a strong preference for the chamber associated with stimulation of the sweet projections.

The senses of taste and smell function as the principal gateways for assessing the attraction to, and palatability of, food cues. In its most fundamental state, taste mediates innate consummatory and rejection behaviours, while also allowing an animal to learn the association of food sources with hardwired tastant-dependent actions. Here we studied the neural basis for innate responses to sweet and bitter, and showed that the taste cortex and the amygdala function as two essential, but distinct, neural stations for identifying tastants and for imposing valence on sweet and bitter.

 

Recent molecular studies have identified distinct populations of neurons in the amygdala that may serve as neural substrates for a wide range of positive and negative hedonic responses. In this study, we show that sweet and bitter cortical fields exhibit separate projection targets in the amygdala, and that photoactivation of these cortico-amygdalar projections evokes opposing responses. However, these can be experimentally dissociated from the cortex, such that animals may recognize a ‘taste stimulus’ but remain oblivious to its valence. Together, these results provide an anatomical substrate for imposing hedonic value to sweet and bitter, and the basic logic for the generation of hardwired, stereotypic attractive and aversive taste responses.

 

The amygdala is known to provide representations of Pavlovian associations, such that innately rewarding and aversive tastants may also function as unconditioned stimuli in conditioning protocols. Therefore, in addition to imposing valence on tastants, the amygdala probably links taste valence to other stimuli so that associative memories can be formed, and thereby appropriate valence-specific behaviour may be elicited by previously neutral cues from other modalities that would now predict a bitter or sweet tastant. Notably, the sweet and bitter cortex project to several additional brain areas, including those involved in feeding, motor systems, multisensory integration, learning and memory. In the future, it will be exciting to unravel how these circuits come together to drive innate and learned responses.

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