Researchers Discover Brain Circuit That Could Reverse Anxiety and Social Withdrawal - Video

A tiny brain circuit may hold the key to switching anxiety and social withdrawal on or even reversing them, according to a new study in mice.

Researchers at the Institute for Neurosciences (IN) identified a specific group of neurons in the amygdala that appears to regulate anxiety, depression-like behaviors, and social interaction. Their findings, published in iScience, suggest that correcting imbalances in this circuit could become a new strategy for treating emotional disorders.

The team focused on genetically engineered mice with unusually high activity of the Grik4 gene, which increases the number of GluK4 glutamate receptors and makes certain neurons overly excitable. These mice displayed anxiety, social withdrawal, and other behaviors similar to symptoms seen in conditions such as autism and schizophrenia.

Researchers then restored normal Grik4 activity in the basolateral amygdala, a brain region involved in processing emotions. This rebalanced communication with inhibitory neurons in the centrolateral amygdala significantly reduced anxiety-like behaviors and improved social interaction.

Behavioral tests showed that treated mice became more willing to explore unfamiliar environments and interact with other mice. Electrophysiological recordings also confirmed that neural activity returned to a healthier pattern.

To determine whether the discovery applied beyond a single genetic model, the scientists tested the same approach in normal mice that naturally exhibited high anxiety. The intervention also reduced anxiety in these animals, suggesting the circuit may play a broader role in emotional regulation.

However, not every symptom improved. The mice continued to show problems with object recognition memory, indicating that other brain regions, such as the hippocampus, may contribute to cognitive deficits.

Although the findings are limited to animal models, researchers believe the study identifies a promising neural pathway that could one day lead to more targeted treatments for anxiety, depression, and other psychiatric disorders by focusing on specific brain circuits rather than the entire brain.

REFERENCE: Alvaro García, M. Isabel Aller, Ana V. Paternain, Juan Lerma. Central role of regular firing neurons of centrolateral amygdala in affective behaviors. iScience, 2025; 28 (6): 112649 DOI: 10.1016/j.isci.2025.112649