Food poisoning triggers lifelong changes in the brain

A single bad food experience can be enough to change eating habits for a lifetime. Now, researchers have identified the precise brain region responsible for this powerful type of memory in mice, offering insights into how the brain links cause and effect when there’s a delay between them – like getting sick hours after a meal. 

This discovery may not only explain why certain foods suddenly become unpalatable but could also inform research into other lasting memory associations, including those involved in trauma and PTSD.

The new findings come from neuroscientists at Princeton University who set out to explore the brain mechanisms behind “one-shot learning,” where a single event creates a long-term memory. 

“I haven’t had food poisoning in a while, but now whenever I talk to people at meetings, I hear all about their food poisoning experiences,” said lead author Christopher Zimmerman, a postdoctoral fellow at the Princeton Neuroscience Institute. 

Inspired by such anecdotes, Zimmerman and his colleagues developed an experiment to understand how the brain forms food aversions even when illness sets in long after eating.

Effects of food poisoning in the brain

Working in the lab of professor Ilana Witten, Zimmerman began by introducing mice to a new flavor – grape Kool-Aid. “It’s a better model for how we actually learn,” he explained. 

“Normally, scientists in the field will use sugar alone, but that’s not a normal flavor that you would encounter in a meal. Kool-Aid, while it’s still not typical, is a little bit closer since it has more dimensions to its flavor profile.”

Mice were trained to poke their noses into a port to receive a drop of the drink. Half an hour later, they were given an injection to induce temporary illness, mimicking food poisoning. 

When offered a choice two days later between Kool-Aid and plain water, they strongly avoided the former – evidence that the unpleasant outcome had left a strong impression. 

But what most intrigued the team was discovering which part of the brain was responsible for this aversive memory: the central amygdala.

“If you look across the entire brain, where novel versus familiar flavors are represented, the amygdala turns out to be a really interesting place because it’s preferentially activated by novel flavors at every stage in learning,” Zimmerman said. 

“It’s active when the mouse is drinking, when the mouse is feeling sick later, and then when the mouse retrieves that negative memory days later.”

Memories of food poisoning in the brain

The central amygdala is a small structure located deep within the brain, known for processing emotional learning, particularly fear.

The amygdala also receives a wide range of sensory information, including taste and smell, making it a logical – but previously unconfirmed – candidate for processing food-related memories.

Zimmerman recalled the thrill of the discovery: “I remember making the plot from the first animal and sharing it on Slack with Ilana. She was at my desk a minute later to talk about how exciting this is.” 

That initial result was just the beginning. With more data, the researchers confirmed that the central amygdala plays a central role at every point in the learning process – when the flavor is first encountered, when sickness occurs, and when the memory is retrieved later.

From the gut to the brain

To understand how the feeling of illness connects to memory, the team followed clues from earlier studies. They identified specialized cells in the hindbrain that produce a protein called CGRP. These cells send direct signals to the central amygdala, forming a neural bridge between the gut and the brain. 

When the researchers stimulated these cells 30 minutes after the mice had tasted Kool-Aid – without inducing actual illness – the mice still developed the same aversion.

Even more striking was the finding that sickness appeared to reactivate the same neurons that had responded to the Kool-Aid in the first place. 

“It was as if the mice were thinking back and remembering the prior experience that caused them to later feel sick,” Witten said. “It was very cool to see this unfolding at the level of individual neurons.”

The researchers propose that novel flavors may “tag” neurons in the amygdala, priming them to remain sensitive to signals from the body for several hours after eating. 

If the animal then experiences sickness during this window, the brain reactivates the tagged neurons and forges a lasting association between the flavor and the illness.

Implications beyond the dinner table

Although the study focused on food aversion, the findings point to a broader framework for how the brain learns to link events separated by time – a process that’s not well understood. 

“Often when we learn in the real world, there’s a long delay between whatever choice we’ve made and the outcome. But that’s not typically studied in the lab, so we don’t really understand the neural mechanisms that support this kind of long delay learning,” Zimmerman said. 

“Our hope is that these findings will provide a framework for thinking about how the brain might leverage memory recall to solve this learning problem in other situations.”

In addition to shedding light on everyday behaviors – like swearing off oysters after one bad experience – this research could have implications for how we understand trauma.

Much like food poisoning, traumatic events are often followed by symptoms only after a delay, and yet they still form vivid, persistent memories in the brain.

By identifying the precise brain pathways involved in one-shot memory formation, scientists are a step closer to understanding how such associations are wired – and possibly how they might be rewired in the future.

The study is published in the journal Nature,

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