Maybe it was a sound that startled you, or a place that still made your stomach twist, despite knowing you’re safe. That lingering fear, that emotional hangover, isn’t just “in your head.” It's tied to how your brain learns—and unlearns—fear. Now, a new study suggests that the key to letting go of fear might lie in a surprising source: dopamine, the same hormone usually linked to pleasure and reward.
In an exciting new study in mice, researchers at MIT found that when danger fades, the brain sends out a kind of internal “all-clear” signal—and this signal is powered by dopamine moving along a specific pathway in the brain. When this circuit is working properly, it helps you calm down and feel safe again. But when it’s not, the fear can stick around, which may contribute to anxiety or post-traumatic stress disorder (PTSD).
“Dopamine is essential to initiate fear extinction ,” said Michele Pignatelli di Spinazzola, co-author of the study from the lab of senior author Susumu Tonegawa, Picower Professor of biology and neuroscience at the RIKEN-MIT Laboratory for Neural Circuit Genetics and a Howard Hughes Medical Institute (HHMI) Investigator.
This latest discovery builds on earlier research from 2020 by the same lab, which showed that fear learning and unlearning happen through a kind of tug-of-war between two different types of neurons in the brain’s amygdala—an area that handles emotions.
When a mouse experiences something scary, like a small foot shock, one group of neurons stores that memory. These are the Rspo2 neurons, located in the front part of the amygdala. But when the mouse later learns that it’s safe, like returning to the same place and getting no shock, a different group of neurons steps in. These are the Ppp1r1b neurons in the back part of the amygdala, and they build a new memory that overrides the fear.
What’s even more interesting is that these "calming" Ppp1r1b neurons are also linked to how we feel rewards. That might explain why feeling safe again can actually feel good—it’s like the brain rewarding us for recognizing safety.
The role of dopamine in all of this
In this new study, led by former lab members Xiangyu Zhang and Katelyn Flick, the researchers dug deeper into what makes those fear-extinguishing neurons in the amygdala activate in the first place.
“Our study uncovers a precise mechanism by which dopamine helps the brain unlearn fear,” said Zhang. “We found that dopamine activates specific amygdala neurons tied to reward, which in turn drive fear extinction. We now see that unlearning fear isn’t just about suppressing it—it’s a positive learning process powered by the brain’s reward machinery. This opens up new avenues for understanding and potentially treating fear-related disorders like PTSD.”
How did the study happen?
To find out how dopamine behaves during fear and safety learning, the team used a method to watch it in real time inside the brain. Mice went through a simple three-day experiment:
Day 1: They received a few mild shocks in a new enclosure.
Day 2: They returned to the same place, but this time got no shocks. At first, they froze in fear. But after about 15 minutes, they began to relax.
Day 3: They came back again to test if the fear was truly gone.
The results were striking. On the first day, dopamine was more active in the Rspo2 neurons (the fear memory holders). But when the expected shocks didn’t come on day two and the mice began to relax, dopamine became more active in the Ppp1r1b neurons. And the mice that showed the strongest reduction in fear also had the highest dopamine activity in those calming neurons.
What does this mean for mental health ?
While the researchers caution that fear extinction happens across multiple areas in the brain, not just this one circuit, this specific dopamine pathway could become an important focus for future treatments for anxiety and PTSD.
In an exciting new study in mice, researchers at MIT found that when danger fades, the brain sends out a kind of internal “all-clear” signal—and this signal is powered by dopamine moving along a specific pathway in the brain. When this circuit is working properly, it helps you calm down and feel safe again. But when it’s not, the fear can stick around, which may contribute to anxiety or post-traumatic stress disorder (PTSD).
“Dopamine is essential to initiate fear extinction ,” said Michele Pignatelli di Spinazzola, co-author of the study from the lab of senior author Susumu Tonegawa, Picower Professor of biology and neuroscience at the RIKEN-MIT Laboratory for Neural Circuit Genetics and a Howard Hughes Medical Institute (HHMI) Investigator.
When a mouse experiences something scary, like a small foot shock, one group of neurons stores that memory. These are the Rspo2 neurons, located in the front part of the amygdala. But when the mouse later learns that it’s safe, like returning to the same place and getting no shock, a different group of neurons steps in. These are the Ppp1r1b neurons in the back part of the amygdala, and they build a new memory that overrides the fear.
What’s even more interesting is that these "calming" Ppp1r1b neurons are also linked to how we feel rewards. That might explain why feeling safe again can actually feel good—it’s like the brain rewarding us for recognizing safety.
The role of dopamine in all of this
In this new study, led by former lab members Xiangyu Zhang and Katelyn Flick, the researchers dug deeper into what makes those fear-extinguishing neurons in the amygdala activate in the first place.
“Our study uncovers a precise mechanism by which dopamine helps the brain unlearn fear,” said Zhang. “We found that dopamine activates specific amygdala neurons tied to reward, which in turn drive fear extinction. We now see that unlearning fear isn’t just about suppressing it—it’s a positive learning process powered by the brain’s reward machinery. This opens up new avenues for understanding and potentially treating fear-related disorders like PTSD.”
How did the study happen?
To find out how dopamine behaves during fear and safety learning, the team used a method to watch it in real time inside the brain. Mice went through a simple three-day experiment:
Day 1: They received a few mild shocks in a new enclosure.
Day 2: They returned to the same place, but this time got no shocks. At first, they froze in fear. But after about 15 minutes, they began to relax.
Day 3: They came back again to test if the fear was truly gone.
The results were striking. On the first day, dopamine was more active in the Rspo2 neurons (the fear memory holders). But when the expected shocks didn’t come on day two and the mice began to relax, dopamine became more active in the Ppp1r1b neurons. And the mice that showed the strongest reduction in fear also had the highest dopamine activity in those calming neurons.
What does this mean for mental health ?
While the researchers caution that fear extinction happens across multiple areas in the brain, not just this one circuit, this specific dopamine pathway could become an important focus for future treatments for anxiety and PTSD.
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