There’s a sour side to serotonin

Unless you’re in the middle of biting into a delicious Reuben sandwich, you might forget that taste is one of the fundamental senses. “It’s required for our enjoyment of food,” explains Emily Liman, a taste researcher at the University of Southern California in Los Angeles. “Without taste … people stop eating. They don’t enjoy their food.” A life without the sweet jolt of sugar or the savory delights of umami seems, well, tasteless.

When you put that mouthwatering combination of corned beef, Swiss cheese, Thousand Island dressing, sauerkraut and rye in your mouth, the chemicals in the sandwich stimulate taste buds on your tongue and soft palate. Those taste buds connect to the ends of nerve fibers extending delicately into the mouth. Those nerve fibers are the ends of cells located in the geniculate ganglion, a ball of cells nestled up against the ear canal on the side of your head. From there, taste sensations head toward the brain.

Chemical messengers bridge the gap between the taste bud and the end of the nerve fiber. But what chemical is involved depends on the type of cell within the bud. There are three types of taste cells (imaginatively titled I, II and III). Type I is not well-understood, but it may be a kind of support cell for other taste cells. Type II, in contrast, is better known. These taste cells sense the slight bitterness of the rye seeds, the sweet edge of the Thousand Island dressing and the savory umami of the beef. They pass that delightful message on using the chemical ATP.

The lovely sour tang of the sauerkraut is left to type III. Scientists knew that these cells sensed sour by detecting acidity in foods. But the chemical connecting the taste cell to the nerve remained unknown.

The mystery chemical messenger, a new study in mice shows, is one usually associated with mood — serotonin. The findings help us understand one of our more mysterious senses. But they also suggest that some of our taste knowledge may have been hidden, not by lack of interest, but by use of the wrong techniques.

Eric Larson, a cell biologist at the University of Colorado School of Medicine in Aurora, says scientists had long suspected that serotonin was a key player in taste. “It’s been known for a while that type III cells … synthesize and store serotonin,” he says. “You can stain [the taste buds] for serotonin and see it accumulating.”

And the serotonin doesn’t just sit there. In a study published in 2005 in the Journal of Neuroscience, Stephen Roper and colleagues at the University of Miami School of Medicine showed that mouse taste buds release their serotonin, which is presumably acting as a messenger.

A chemical messenger can’t just bump into a cell, though. It has to contact a receptor, fitting into it as a key into a lock, to send the message on. In a new study, Larson and his colleagues set out to find the corresponding lock for the serotonin key. They hooked a potential receptor, serotonin 3, to green fluorescent protein and showed that the nerve terminals in the mouse tongue have serotonin 3 receptors, and these receptors are made by the nerve cells located in the geniculate ganglion. In the presence of sour tastes, the type III taste buds release serotonin, and the nerve cells with serotonin 3 receptors take it up. Larson and his colleague published their results December 2 in the Journal of Neuroscience.

But the finding only emerged after several months of failures. “To report the output of the tongue, you anesthetize the mouse and you record from the nerve,” Larson explains. Usually, he says, taste researchers anesthetize mice with pentobarbital. Pentobarbital is a barbiturate, which stimulates the inhibitory chemical messenger GABA, putting animals (and humans) to sleep. But Larson and his group found an unexpected side effect: “It blocked the serotonin signal,” he says. When mice were anesthetized with the barbiturate, the serotonin effect was barely present. When Larson used another anesthetic, urethane, the signal shot upward.

“When we switched [anesthetics] it was quite surprising,” Larson says. “We were super excited, now our mouse had a phenotype!”

The findings may call into question other taste studies that used pentobarbital, says Liman. “It’s surprising that pentobarbital affected the response,” she says. “The anesthetic may have masked interactions that need to be re-investigated.”

The idea that serotonin was mediating the taste of sour had been proposed before, but “there was no direct evidence,” she says. Now, “all the different pieces of evidence lead to the conclusion that serotonin acts in the taste bud.”

So the next time you face the mouthwatering prospect of a Reuben, think of serotonin. And don’t forget that even seemingly unimportant choices in science — such as the choice of one anesthetic technique over another — can sometimes make all the difference.

Editor’s note: This post was updated on January 25, 2016, to clarify that taste buds contain multiple types of cells.