Summary: A new study reveals how a single food poisoning experience creates long-lasting aversive memories in the brain. Researchers found that mice developed strong aversions to a flavored drink after getting sick, even with a 30-minute delay between consumption and illness.
The central amygdala, a brain region tied to fear and emotion, was active during tasting, illness, and memory recall—highlighting its role in “one-shot” learning. This discovery offers insight into how the brain links distant events, with potential relevance for understanding PTSD and other trauma-based memory formation.
Key Facts:
- Memory Hub Identified: The central amygdala encodes and retrieves aversive food memories.
- Gut-Brain Link: Hindbrain cells with CGRP connect illness signals to memory centers.
- Time-Delayed Learning: The brain tags novel flavors to form associations hours later.
Source: Princeton
We’ve all been there: one bad oyster ruins seafood forever.
Now, Princeton neuroscientists have pinpointed the exact “memory hub” in the brain responsible for these powerful food aversions in mice.
The new results reveal how “one-shot learning”, where a single experience creates lasting memories, unfolds in rodents, which might shed light on how similar memories form in people, such as when a single traumatic event leads to PTSD. As such, work on food poisoning in mice may help potentially inform future clinical treatments in humans.
The findings were published on April 2 in the journal Nature.
Many people can recall a vivid food poisoning experience that’s led them to avoid certain foods that made them ill. Christopher Zimmerman, Ph.D. has heard many such stories.
“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 Zimmerman, lead author of the new paper, and postdoctoral fellow at the Princeton Neuroscience Institute (PNI).
Though the experience is common enough, the mystery that has long puzzled researchers was the time gap. Unlike touching a hot stove and feeling immediate pain, food poisoning involves a significant delay between eating contaminated food and getting sick – what Zimmerman calls the “meal-to-malaise” delay.
Working in the lab of Ilana Witten, Ph.D., professor of neuroscience at PNI, Zimmerman first started to tease out the brain mechanisms behind learning to avoid sickening food by asking mice to try a new flavor they had never encountered before: grape Kool-Aid.
“It’s a better model for how we actually learn,” Zimmerman said.
“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 learned that poking their nose in a special area of their cage would deliver a drop of Kool-Aid. Thirty minutes later after enjoying their first taste of the purple beverage, the mice received a one-time injection causing temporary food poisoning-like illness.
Unsurprisingly, when offered a choice two days later, the mice strongly avoided the once-appealing Kool-Aid and preferred to just drink water. What did stick out to Zimmerman and Witten, however, was where in the brain this juice/illness association was found: the central amygdala.
“If you look across the entire brain, at 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.”
The central amygdala, a small group of cells towards the bottom of the brain involved in emotion and fear learning, also processes a lot of information from the environment, including smells and tastes.
Zimmerman’s results are the first to show how critical the central amygdala is at every step along the way of learning and were striking even with the very first experiment.
“I remember making the plot from the first animal and sharing it on Slack with Ilana,” Zimmerman said. “She was at my desk a minute later to talk about how exciting this is.”
Now that they knew where aversive flavor memories are formed, the team then traced how illness signals from the gut reach the brain.
Based on hints from previous research, they identified specialized hindbrain cells containing a specific protein (CGRP) that directly connect to the central amygdala. Stimulating these cells 30 minutes after a mouse’s Kool-Aid experience created the same aversion as actual food poisoning.
They also found that feeling sick caused the Kool-Aid-activated neurons to reactivate.
“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 team believes novel flavors may “tag” certain brain cells to remain sensitive to illness signals for hours after eating, allowing those cells to be specifically reactivated by sickness, and therefore connect cause and effect despite the time delay.
This research opens new pathways for understanding how the brain forms connections between distant events – with implications beyond understanding how bad shellfish memories are cemented.
“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.”
Funding: Funding for the study was provided by the National Institutes of Health (K99-DA059957, U19-NS104648, U19-NS123716, DP1-MH136573, RF1-MH128776, P50-MH136296), the Howard Hughes Medical Institute, the Simons Collaboration on the Global Brain, the Helen Hay Whitney Foundation, and the Brain Research Foundation.
About this food aversion and neuroscience research news
Author: Dan Vahaba
Source: Princeton
Contact: Dan Vahaba – Princeton
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A neural mechanism for learning from delayed postingestive feedback” by Christopher A. Zimmerman et al. Nature
Abstract
A neural mechanism for learning from delayed postingestive feedback
Animals learn the value of foods on the basis of their postingestive effects and thereby develop aversions to foods that are toxic and preferences to those that are nutritious. However, it remains unclear how the brain is able to assign credit to flavours experienced during a meal with postingestive feedback signals that can arise after a substantial delay.
Here we reveal an unexpected role for the postingestive reactivation of neural flavour representations in this temporal credit-assignment process.
To begin, we leverage the fact that mice learn to associate novel, but not familiar, flavours with delayed gastrointestinal malaise signals to investigate how the brain represents flavours that support aversive postingestive learning.
Analyses of brain-wide activation patterns reveal that a network of amygdala regions is unique in being preferentially activated by novel flavours across every stage of learning (consumption, delayed malaise and memory retrieval).
By combining high-density recordings in the amygdala with optogenetic stimulation of malaise-coding hindbrain neurons, we show that delayed malaise signals selectively reactivate flavour representations in the amygdala from a recent meal.
The degree of malaise-driven reactivation of individual neurons predicts the strengthening of flavour responses upon memory retrieval, which in turn leads to stabilization of the population-level representation of the recently consumed flavour. By contrast, flavour representations in the amygdala degrade in the absence of unexpected postingestive consequences.
Thus, we demonstrate that postingestive reactivation and plasticity of neural flavour representations may support learning from delayed feedback.
