The Biology of Taste Perception & Sugar Craving | Dr. Charles Zuker

Andrew Huberman introduces Dr. Charles Zuker as a professor of biochemistry and molecular biophysics and of neuroscience at Columbia University School of Medicine, and as a leading researcher on perception, meaning how the nervous system turns physical stimuli into the experiences we call smell, taste, vision, touch and hearing. Huberman says Zuker's lab first worked on vision, defining the receptors that convert light into signals the eye and brain can use. In recent years the lab has concentrated on taste, discovering many of the receptors behind sweet, sour, bitter, salty and umami, which Huberman glosses as savoriness. Huberman also credits the lab with work on thirst, meaning how the nervous system decides whether to take in more fluid or reject it.

Huberman frames the lab's work as bridging brain and body. He previews a finding the conversation will return to: besides sugar-sensing neurons in the brain, there is a separate set of neurons that sense sweetness and sugar within the body, and much of the brain-body communication that drives sugar seeking happens below conscious detection. He lists Zuker's memberships in the National Academy of Sciences, the National Academy of Medicine and the American Association for the Advancement of Science. He also notes that Zuker has been a Howard Hughes Medical Institute investigator since 1989, a competitive appointment that he says must be re-earned every five years.

Asked how to think about perception and how it differs from sensation, Zuker starts with the brain itself. He describes it as an organ that weighs maybe 2% of body mass yet consumes anywhere between 25% and 30% of the body's energy and oxygen, and that somehow becomes a mind capable of transforming "fear into courage, conformity into creativity, sadness into happiness." The core problem, in his telling, is that the world is made of real objects, like a glass, a cord or a microphone, while the brain is made only of neurons that understand electrical signals.

Zuker draws a working line between two steps. Detection is what happens when a sugar molecule lands on the tongue and specific cells sense it; at that point, he says, nothing has been perceived. Perception begins when those activated cells signal the brain and the brain turns that signal into an experience that can guide action and behavior. Understanding that transformation, he says, has been the central drive of his career.

That's been the maniacal drive of my entire career in neuroscience. How does the brain ultimately transform detection into perception so that it can guide actions and behaviors?

Huberman asks whether two people perceive the color of the same shirt in the same way. Zuker argues that it follows from his framing that they cannot. If each brain represents the world by encoding and decoding electrical signals, and brains differ, then two people perceive the world differently even when they receive the same sensory cues.

He supports this with a color-matching experiment that he calls simple yet brilliant. Humans have three classes of photoreceptor neurons tuned to blue, green and red, enough to cover the visible spectrum. In the setup, a red projector and a green projector are overlapped on a screen to produce yellow, while a third projector with a filter shows a spectrally pure yellow right beside it. Each participant adjusts the red and green intensity knobs until the mixed yellow matches the pure one, and the knob settings are recorded. Zuker says that if everyone around Battery Park in New York did this, the result would be thousands of different number combinations.

So, for all of us, it's yellow enough that we can use a common language. But for every one of us, that yellow is going to be ever so slightly different.

Zuker also notes a limit on the argument. Color works as a demonstration because its basic elements are known. For senses like sound or smell, he says, it is very hard to design an experiment with the same granularity and clear causality. Two people can each describe the smell of a rose, but there is no way to know whether they experience the same thing. Their accounts overlap enough to agree on its features, yet he holds there is "no question that your experience is different than mine."

Huberman raises an idea he attributes to Marcus Meister at Caltech, from a review he once read: perception's basic job is to sort behavior into outcomes that follow three emotional responses. In Huberman's words, those are "Yum, I like it. Yuck, I hate it. Or meh, whatever." Huberman finds this appealing because the brain is economical despite its high metabolic cost. Perception varies between individuals, yet it works well enough for most people to avoid cliffs and poisons and, one hopes, to enjoy life.

Zuker partly agrees. He says many behaviors can broadly fall into such categories and that this is "100% likely to be the case for animals in the wild," whose choices are distinct: whether to eat something, kill something, or go one way or another. Humans, he argues, left that world long ago and learned to do things they should not be doing. His example comes from taste: an animal in the wild enjoying something bitter is "inconceivable," yet people love tonic water. He concludes that the three-way scheme is "not a bad palate" but overly reductionist for what humans do.

Asked why he moved from vision to taste, Zuker says his goal has always been to understand how the brain works: how it encodes and decodes emotions, memories and actions, how it makes decisions, and how it turns detection into perception. The key in science, he argues, is choosing a question that can be answered. A question that cannot be reduced to an experimental path may produce fun science without solving the problem that matters. He offers the neural basis of empathy, philanthropy or love as questions he would like answered but would not know how to approach at the molecular and circuit level.

Taste, in his account, provides that window. It turns detection into perception, forms memories, creates emotions, and produces different perceptions depending on internal state. He gives two examples: food tastes very different when you are hungry than when you are full, and a taste can bring back a meal from a first date. At the same time, its input-output relationships are relatively simple. He also notes that when he began this work, nothing was known about the molecular basis of taste.

Zuker lists the five generally recognized basic taste qualities: sweet, sour, bitter, salty and umami. He explains umami as a Japanese word meaning yummy or delicious. In nearly every animal species it is the taste of amino acids, and in humans it is mostly associated with MSG, monosodium glutamate. Asked for umami-rich foods, he names seaweed, tomatoes and cheese, and calls umami a great flavor enhancer.

He says the system is appealing to study because it has only five input lines, each with a predetermined meaning. People are born liking sugar and disliking bitter, and he calls these hardwired systems. He adds a qualifier: people can learn to dislike sugar and like bitter. In the wild, though, he describes the valences as 100% predetermined. Sweet, umami and low salt are attractive and draw appetitive responses, while bitter and sour are innately aversive.