The taste system detects 5 major categories of ethologically relevant stimuli (sweet, bitter, umami, sour and salt) and accordingly elicits acceptance or avoidance responses. While these taste responses are innate, the taste system retains a remarkable flexibility in response to changing external and internal contexts. Taste chemicals are first recognized by dedicated taste receptor cells (TRCs) and then transmitted to the cortex via a multi-station relay. I reasoned that if I could identify taste neural substrates along this pathway, it would provide an entry to decipher how taste signals are encoded to drive innate response and modulated to facilitate adaptive response. Given the innate nature of taste responses, these neural substrates should be genetically identifiable. I therefore exploited single-cell RNA sequencing to isolate molecular markers defining taste qualities in the taste ganglion and the nucleus of the solitary tract (NST) in the brainstem, the two stations transmitting taste signals from TRCs to the brain. How taste information propagates from the ganglion to the brain is highly debated (i.e., does taste information travel in labeled-lines?). Leveraging these genetic handles, I demonstrated one-to-one correspondence between ganglion and NST neurons coding for the same taste. Importantly, inactivating one ‘line’ did not affect responses to any other taste stimuli. These results clearly showed that taste information is transmitted to the brain via labeled lines. But are these labeled lines aptly adapted to the internal state and external environment? I studied the modulation of taste signals by conflicting taste qualities in the concurrence of sweet and bitter to understand how adaptive taste responses emerge from hardwired taste circuits. Using functional imaging, anatomical tracing and circuit mapping, I found that bitter signals suppress sweet signals in the NST via top-down modulation by taste cortex and amygdala of NST taste signals. While the bitter cortical field provides direct feedback onto the NST to amplify incoming bitter signals, it exerts negative feedback via amygdala onto the incoming sweet signal in the NST. By manipulating this feedback circuit, I showed that this top-down control is functionally required for bitter evoked suppression of sweet taste. These results illustrate how the taste system uses dedicated feedback lines to finely regulate innate behavioral responses and may have implications for the context-dependent modulation of hardwired circuits in general.

The moment that a tasty substance enters an animal’s mouth, the clock starts ticking. Taste information transduced on the tongue signals whether a potential food will nourish or poison, and the animal must therefore use this information quickly if it is to decide whether the food should be swallowed or expelled. The system tasked with computing this important decision is rife with cross-talk and feedback—circuitry that all but ensures dynamics and between-neuron coupling in neural responses to tastes. In fact, cortical taste responses, rather than simply reporting individual taste identities, do contain characterizable dynamics: taste-driven firing first reflects the substance’s presence on the tongue, and then broadly codes taste quality, and then shifts again to correlate with the taste’s current palatability—the basis of consumption decisions—all across the 1-1.5 seconds after taste administration. Ensemble analyses reveal the onset of palatability-related firing to be a sudden, nonlinear transition happening in many neurons simultaneously, such that it can be reliably detected in single trials. This transition faithfully predicts both the nature and timing of consumption behaviours, despite the huge trial-to-trial variability in both; furthermore, perturbations of this transition interfere with production of the behaviours. These results demonstrate the specific importance of ensemble dynamics in the generation of behaviour, and reveal the taste system to be akin to a range of other integrated sensorimotor systems.