Scientists have uncovered how a specific group of brain cells deep in the amygdala—a region that helps control emotions—can drive anxiety, depression, and social withdrawal.
Even more striking, they found that restoring balance in this tiny brain area can reverse these behaviors.
The new study, led by Juan Lerma and his team at the Institute for Neurosciences (IN) in Spain, was published in the journal iScience.
The amygdala has long been known for its role in fear and emotional processing, but this study takes things further.
The researchers identified a distinct population of neurons in the basolateral amygdala whose activity alone can cause pathological behaviors. When these neurons become too active, they can throw the emotional system off balance, leading to anxiety and social problems.
The team used genetically modified mice that overproduce a brain receptor called GluK4, which is controlled by the Grik4 gene. This overproduction makes the neurons more excitable and disrupts communication between brain regions.
These mice showed strong signs of anxiety and social withdrawal—behaviors that resemble symptoms seen in humans with autism, schizophrenia, and other mood disorders.
To fix this, the researchers used genetic tools to normalize Grik4 expression only in the neurons of the basolateral amygdala. This single adjustment restored proper signaling with another group of inhibitory neurons in the centrolateral amygdala, known as “regular firing neurons.”
When the balance of activity was restored, the anxious and antisocial behaviors disappeared. “That simple adjustment was enough to reverse anxiety-related and social deficit behaviors, which is remarkable,” said Álvaro García, the first author of the study.
The scientists confirmed their findings using advanced electrophysiological recordings, which measure how neurons communicate, and behavioral tests that evaluate anxiety and depression.
For instance, they observed whether mice preferred open or closed spaces (a sign of anxiety) and how they interacted with unfamiliar mice (a sign of social interest). After the treatment, the mice became calmer and more sociable, showing a clear link between brain balance and emotional behavior.
Interestingly, when the team applied the same technique to normal mice that naturally had higher anxiety levels, the treatment also reduced their anxiety.
This suggests that the mechanism is not limited to genetically engineered mice—it may represent a general principle of how the brain controls anxiety and emotion. “This validates our findings and gives us confidence that the mechanism we identified is not exclusive to a specific genetic model,” Lerma explained.
However, the researchers also noticed that some cognitive functions, like object recognition memory, did not fully recover. This implies that other regions of the brain, such as the hippocampus, might also play a role in emotional and cognitive disorders.
Still, the main finding—that adjusting the excitability of a small group of neurons in the amygdala can normalize emotional behavior—opens up exciting new possibilities for targeted treatments.
In the broader picture, this research shows how modern neuroscience is beginning to move away from one-size-fits-all drug treatments and toward more precise, circuit-based approaches. Instead of broadly altering brain chemistry, future therapies might directly target the overactive or underactive cells responsible for emotional imbalance.
This kind of targeted neural modulation could one day lead to safer, faster-acting treatments for anxiety, depression, and social disorders.
The study was supported by several Spanish and European research agencies, including the Spanish State Research Agency, the Severo Ochoa Excellence Program, and the European Regional Development Fund.
According to Lerma, the next step is to explore how similar mechanisms operate in the human brain and whether the same strategy could help people with chronic anxiety or depression.
In reviewing the findings, this study stands out for demonstrating that emotional disorders can result from very specific disruptions in brain activity—and that restoring balance, even in a small neural circuit, can have powerful effects.
If these results can be confirmed in humans, they may pave the way for a new generation of brain-based treatments that restore emotional stability without heavy medication.
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The study is published in iScience.
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