The experience of taste is both essential and ephemeral. It’s the reliable bite of your morning coffee, and it’s the charred sweetness of your first campfire marshmallow, so deeply associated with a particular setting that you forget about it until another marshmallow and another campfire shocks it back into your mind. There’s so much tied up in taste that it’s easy to overlook the fact that our ancestors likely evolved it as a way to make sure we recognized sweet foods with lots of calories and avoided bitter, poisonous things after trying a tiny bite. We are born with a love of sweetness and a dislike of bitterness (though humans are able, through experience, to rework these if we so wish).
How exactly the brain receives the message of sweetness or bitterness, declares it good or bad, and then has us eat more or spit something out is a profound question, linking together the basic biology of taste buds on the tongue and the shadowy tracery of neurons leading from the taste cells back into the brain. For years now, Charles Zuker and his lab at Columbia University’s Zuckerman Institute have been following that tracery, publishing new papers as the trail leads them through each successive brain structure involved in perception.
In their latest study, published in Nature on Wednesday, they report that from the brain’s taste cortex, the neurons carrying the message of bitterness or sweetness take different routes to the amygdala, a region known for consolidating and modulating emotion. In a series of experiments in mice, they show that they can use this information to remove the positive connotation from sweetness and the negative from bitterness.
In a previous study, to test their understanding of how a message is labeled as sweet or bitter, the researchers rewired mice so that the animals’ sweet neurons fired when they tasted bitterness. As a result, these mice would happily slurp down water laced with bitter substances. The group was even able to get other mice to respond as if they had drunk a bitter fluid—wiping their muzzles vigorously as if it get rid of the taste—solely by triggering their bitter neurons, without having them drink anything.
All this demonstrated that bitter and sweet have very distinct, fairly easily manipulated signals in the brain. But the experiments didn't tell the researchers anything about why sweetness should be favored and bitterness spurned—how they are assigned these positive and negative values in the brain, once what they are has been established. “Taste has two incredibly salient features,” says Zuker. “One is the identity, and the other is the valence, or hedonic, value.”
The researchers continued to follow the trail of cells carrying taste information through the brain. As they reached the amygdala, they found that the bitter messages came in from a different set of neurons than the sweet. They engineered mice in which the neurons bearing those messages could be triggered by laser light, and then set the mice up so that a laser would turn on when they licked an empty water-bottle spout. If they got a positive feeling from the laser, they would lick more; if they got a negative feeling, less. Indeed, mice whose sweet neurons were triggered by the laser licked with abandon. Mice whose bitter neurons were activated did not.
All of this took place without the mice drinking anything. The only thing happening was the activation of neurons in the amygdala. To see whether mice whose amygdala wasn’t firing could tell sweet and bitter apart, without preferring one over the other, the researchers first trained mice to indicate whether a fluid they were drinking was bitter or sweet by moving to the left or the right after taking a sip. Then they gave the mice a drug that kept the amygdala quiet. Lo and behold, the mice continued to be able to identify whether what they were tasting was bitter or sweet—but they did not show any interest in sweetness or any aversion to bitterness.
The pathway a message takes into the amygdala helps define whether a sensation is flagged as a good one or a bad one, the results indicate. As the researchers continue their progress on the trail of taste, they are hoping to uncover what happens next, after a bite of cake or a swig of spoiled milk is given its value. Some neurons doubtless circle around to others that control motor function, so a foul-tasting substance can be spit out and a pleasant one swallowed eagerly. But what Zuker is most interested in is memory. “One bad oyster is all it takes for you to be actively avoiding oysters for the next 12 months,” he says. “A strong negative taste experience will stay with you for ... a long, long time. So how? Where is this signal going to?