What a Mouse’s Mixed-Up Taste Buds Say About the Brain


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Foodies everywhere live in fear of the tongue burn. Every time I forget to cool off a cup of hot coffee, I worry I’m killing off taste buds, incrementally deadening my flavor detection capabilities. But I shouldn’t, really: Scalding your tongue probably doesn’t affect your sense of taste much, and even if it did, it wouldn’t matter for long. Individual taste bud cells only live between a week and a month, and new ones grow in their place at about the same rate.

That turnover keeps your taste buds fresh and sprightly. The amazing thing is that even with all those brand-new cells, your coffee still tastes roughly the same as it did two years ago. Nutty, earthy, a little bitter. That’s because new taste-sensing cells are constantly reconnecting to your neurons—in similar configurations, over and over again—correctly reporting the taste of your food to your brain.

In a paper published Wednesday in Nature, researchers have peered into the hardware behind that signal fidelity. Their findings don’t completely solve the mystery of how the brain keeps track of different tastes. But they’ve identified a class of proteins that guide neurons to the right taste cells in mice, so new sweet receptors still ping the right neurons when they eat sugar. The group could even use the same system to trick a mouse’s brain into thinking a bitter or sour treat actually tasted sweet.

Charles Zuker, a neuroscientist at Columbia University’s Zuckerman Institute and a coauthor of this paper, has talked about the five tastes a lot. You can tell, because he smooshes their names together the way some parents call all of their kids at once: “sweetsourbittersaltyandumami.” When a flavor molecule lands on your tongue, it binds to a chemically sensitive taste receptor at the tip of one of your taste buds—each bud bundles dozens of these receptors together. Some receptors are specific to one of the five tastes, while others can respond to a couple of them. For all receptor cells, though, binding a flavor chemical sets off a Rube Goldberg machine of cellular signals, eventually alerting neurons that register what you’re eating as salty or sweet.

To understand how taste receptors might connect to the right neurons, Zuker’s colleague Hojoon Lee designed transgenic mice with glowing tongue cells. Specifically, sweet receptors would fluoresce blue, while their bitter sensing cells glowed green. After color-sorting those cells, he sequenced their RNA, hoping to find a significant difference between the two receptor types.

One class of molecules, semaphorins—named for semaphores, sign bearers—stood out. The showed up in both bitter and sweet taste receptor cells, but in slightly different forms.

Semaphorins aren’t unique to the taste system. They act as sign posts all over the body, showing neurons where to attach during development. “If you think about a neuron in your spinal cord that has to enervate your toe muscle, it cannot just go down your leg, it had to be guided down your leg, when you were an embryo,” says Nirupa Chaudhari, a University of Miami neuroscientist who wasn’t involved in the study. The taste receptor cells were similarly sending up flares for neurons, “so that a sweet taste cell will connect to a sweet neuron and a bitter taste cell will connect to a bitter neuron,” says Zuker.

To test that theory, Lee engineered another round of transgenic mice—this time, without bitter-specific semaphorins—and tracked how their neurons responded to sugar and quinine. He tracked the neurons’ behavior by injecting an engineered virus into the mouse’s brain stem to make its neurons fluoresce when they spike, and watched them glow through a millimeter-sized hole covered with a 10x magnification lens. He expected that without the sign posts, the bitter-sensing neurons wouldn’t know where to connect to taste receptors.

He was right: Without the bitter semaphorins to guide them, the bitter-responsive neurons responded to quinine and to other flavors. And measured in number of mouse licks, the mice could no longer tell the difference between quinine-infused water and plain water. Lest the mice simply be developing a taste for gin and tonic, he also tested other crossovers. Sure enough, putting mismatched semaphorins into other taste receptors could make sweet-tasting neurons light up in response to bitter flavors, or sour-tasting neurons light up in response to sweet.

The way neurons respond to different taste receptors isn’t totally hammered out, says Chaudhari. It’s not clear if each neuron relays signals about only one taste or many tastes, and their response could depend on more than one factor, like the concentration of a certain flavor, she points out. But these proteins do appear to play an important role in guiding neurons to the right receptor. The next time you scald your tongue, you can thank the semaphorins.

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