For Neuroscientist Charles Zuker, Brain Science is a Matter of Taste

Charles Zuker has devoted his career to unraveling the neurobiology of the senses—especially taste, but he is quick to tell you that it’s not because of some

Charles Zuker,
Credit: Columbia University

inherent fascination with bitter, sweet, and salty truths. “The fact is that we don’t study the senses simply to understand the senses,” says Zuker, a professor of biochemistry and molecular biophysics and of neuroscience. “We study the senses as an entry point—a tractable problem—in dissecting the mysteries of the brain.” And taste, he notes, is a particularly elegant system for plumbing those mysteries.

The senses are the conduits of the external world into our brain. What we see, hear, touch, taste, and smell are processed in the brain and become the basis for an internal representation of the outside world. “The biggest challenge in the field of sensory biology is to understand how you make that representation, how you store it, how you recall it, how you modify it by experience and emotion, and how it all comes together to orchestrate and guide behavioral choices,” says Zuker, who is on the faculty of Columbia's new Mortimer B. Zuckerman Mind Brain Behavior Institute as well as the University's Kavli Institute for Brain Science.

The sense of taste offers some unique advantages for scientists trying to solve these puzzles. First, it relies on just five basic inputs (albeit in myriad combinations): sweet, sour, bitter, salty, and umami—a meat-like flavor first identified in 1908 by Japanese scientist Kikunae Ikeda. Compare this limited palette with the vast array of smells, sights, and sounds that our other senses must process. Second, each of the five basic flavors has intrinsic value. From birth, we love things that are sweet, slightly salty, and umami, and we reject things that are bitter, sour, or very salty (though later in life, we may override these aversions and acquire a taste for coffee, grapefruit, and anchovies).

Because of our inborn preferences, says Zuker, “the taste system affords a beautiful platform for understanding how the brain encodes innate attractive and aversive behaviors, how it transforms a signal into like versus dislike.” A 2013 study by Zuker and his associates found, for example, that the cellular and molecular basis for rejecting extremely salty foods involves activating the aversive pathways for sour and bitter tastes. Earlier work by Zuker showed that each of the basic flavors can be mapped to specific neurons in the brain.

Zuker and the researchers in his lab often work with genetically altered mice to explore how the brain processes taste and guides behavior. “You can manipulate neural circuits in mice to change the perception of taste such that the mice now prefer bitter to sweet or find sweet no more appealing than water,” he says. His research also looks at how taste may be modified by internal states such as hunger, satiety, emotion, and expectation. “Each of these internal states alters the way something tastes,” he observes. “When you are very hungry, something ordinary can be exquisite.” Fear and sadness can have the opposite effect. “Severely depressed patients often claim that food seems unpalatable.”

The grandchild of Eastern European Jews who fled to Chile to escape the Holocaust, Zuker took an early interest in biology. He remembers playing with microscopes as a small boy and receiving a binocular microscope as a bar mitzvah gift. “For the first time, I could look at minute things with both eyes. That opened up a whole new world."

Zuker began college at age 16 and entered graduate school at MIT at 19. By then he had fallen under the spell of molecular biology. He had a long and successful career at the University of California, San Diego, and has been a Howard Hughes Medical Institute Investigator since 1989, and a Senior Fellow at the Janelia Research Center since its inception. In 2009, he moved to Columbia in order to be part of what is now the Mortimer B. Zuckerman Mind Brain Behavior Institute, a cross-disciplinary center for brain science that will occupy the first building on Columbia’s new Manhattanville campus. “I have no doubt that after putting together such a remarkable group of people in Renzo Piano’s extraordinary Greene Science Center, something magical will happen,” says Zuker.

Like most Zuckerman Institute investigators, Zuker is focused on basic science, but he knows his work could have valuable applications. The elderly often lose interest in eating in part because their taste receptor cells have deteriorated. “This is not a trivial problem,” says Zuker, and a better understanding of the taste system could help yield solutions. It might also help patients with eating disorders, and in applications in battling diabetes and obesity. For instance, “Can one find find ways to make a little bit of sweet taste like a lot of sweet?” he asks.

But the main driver for Zuker’s work is to understand the brain, the most complex organ on Earth. “Faith, happiness, hunger, hope, creativity, ingenuity—all of that is nothing but electrical signals, the only language the brain understands. How, for example, do we transform fear into courage? Well, it happens in your brain and it’s encoded somewhere in those 100 billion neurons.”

—by Claudia Wallis

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