Mouse brains hint at why it’s so hard to forget food poisoning

Food poisoning isn’t an experience you’re likely to forget — and now, scientists know why. A study published April 2 in Nature has unraveled neural circuitry in mice that makes food poisoning so memorable.

“We’ve all experienced food poisoning at some point … And not only is it terrible in the moment, but it leads us to not eat those foods again,” says Christopher Zimmerman of Princeton University.

Luckily, developing a distaste for foul food doesn’t take much practice — one ill-fated encounter with an undercooked enchilada or contaminated hamburger is enough, even if it takes hours or days for symptoms to set in. The same is true for other animals, making food poisoning one of the best ways to study how our brains connect events separated in time, says neuroscientist Richard Palmiter of the University of Washington in Seattle.

Mice usually need an immediate reward or punishment to learn something, Palmiter says; even just a minute’s delay between cause (say, pulling a lever) and effect (getting a treat) is enough to prevent mice from learning. Not so for food poisoning. Despite substantial delays, their brains have no trouble associating an unfamiliar food in the past with tummy torment in the present.

Researchers knew that a brain region called the amygdala represents flavors and decides whether or not they’re gross. Palmiter’s group had also shown that the gut tells the brain it’s feeling icky by activating specific “alarm” neurons, called CGRP neurons. “They respond to everything that’s bad,” Palmiter says.

Now, after five years of experiments, Zimmerman and his colleagues understand how these processes interact to burn dangerous tastes into memory.

The team had mice drink grape Kool-Aid and, 30 minutes later, injected the rodents with lithium chloride to make them ill. Two days later, they gave the mice grape Kool-Aid again. The team ran many variations on this simple experiment and peeked inside the mice’s brains at each step. In some experiments, the researchers euthanized mice and made their brains transparent to image them in 3-D. In others, the researchers genetically engineered mice so their CGRP neurons could be turned on and off using light and used tiny electrodes to track the activity of small patches of the amygdala while the mice were alive.

When the mice got sick after drinking grape Kool-Aid for the first time, their CGRP neurons reactivated and dialed up the sensitivity of neurons in the amygdala that represented the flavor. Those same neurons reactivated when the mice encountered grape Kool-Aid again later, suggesting that reinforcement from CGRP neurons helps the amygdala remember dangerous foods. This effect didn’t occur in mice that had tasted grape Kool-Aid before without getting sick; only first-time exposures left a lasting impression. In humans, the novelty that cues us to remember food poisoning could be a bit more complex than taste alone: A spice blend, a new restaurant, or any other unfamiliar element of an eating experience can ick us out.

And the results go beyond food poisoning. While the study was largely motivated by “pure curiosity,” says coauthor Ilana Witten, also a Princeton neuroscientist, “it could be curiosity that’s very relevant to mental health.”

Similar neural circuits might explain why bad new experiences are so memorable in general, Witten says. In addiction and trauma, this phenomenon, known as aversive learning, seems to run awry; the neural circuits supposed to keep us safe end up causing harm. Learning to control those circuits could lead to new treatments.