Zhang Juen

In humans, the detection and ultimately the perception of sweetness begin in the oral cavity, where taste receptor cells (TRCs) dedicated to sweet-sensing interact with sugars, artificial sweeteners, and other sweet-tasting chemicals. Human sweet TRCs express on their cell surface a sweet receptor that initiates the cascade of signaling events responsible for our strong attraction to sweet stimuli. Here, we describe the cryo-electron microscopy (cryo-EM) structure of the human sweet receptor bound to two of the most widely used artificial sweeteners-sucralose and aspartame. Our results reveal the structural basis for sweet detection, provide insights into how a single receptor mediates all our responses to such a wide range of sweet-tasting compounds, and open up unique possibilities for designing a generation of taste modulators informed by the structure of the human receptor.

Real-time decisions on what foods to select for consumption, particularly in the wild, require a sensitive sense of taste and an effective system to maintain short-term taste memories, also defined as working memory in the scale of seconds. Here, we used a behavioral memory assay, combined with recordings of neural activity, to identify the brain substrate for short-term taste memories. We demonstrate that persistent activity in taste cortex functions as an essential memory trace of a recent taste experience. Next, we manipulated the decay of this persistent activity and showed that early termination of the memory trace abolished the memory. Notably, extending the memory trace by transiently disinhibiting taste cortical activity dramatically extended the retention of a short-term taste memory. Together, our results uncover taste cortex as a neural substrate for working memory and substantiate the role of sensory cortex in memory-guided actions while imposing meaning to a sensory stimulus.