A Spanish research team found that reducing expression of the GRIK4 gene in a small population of amygdala neurons reversed anxiety-like, depressive and social-deficit behaviors in mice. The intervention lowered levels of the GluK4 receptor and normalized activity in a specific neuronal population, restoring typical anxiety and social behavior. Treated mice still had persistent object-recognition memory problems, indicating other brain systems were not fully repaired. The work, published in iScience, suggests targeted neural-circuit approaches could offer new directions for treating anxiety but requires further validation in humans.
Scientists Pinpoint Amygdala Neurons That Drive Anxiety — Reducing GRIK4 Calms Symptoms in Mice
A Spanish research team found that reducing expression of the GRIK4 gene in a small population of amygdala neurons reversed anxiety-like, depressive and social-deficit behaviors in mice. The intervention lowered levels of the GluK4 receptor and normalized activity in a specific neuronal population, restoring typical anxiety and social behavior. Treated mice still had persistent object-recognition memory problems, indicating other brain systems were not fully repaired. The work, published in iScience, suggests targeted neural-circuit approaches could offer new directions for treating anxiety but requires further validation in humans.
02:05 PM, 11/14/2025Health
Targeting a small group of amygdala neurons reverses anxiety-like behavior in mice
Anxiety disorders are the most common mental-health conditions worldwide, affecting an estimated 360 million people. A team from the Spanish National Research Council and Miguel Hernández University of Elche (CSIC-UMH) reports a promising advance: rebalancing a specific population of neurons in the amygdala eliminated anxiety-like, depressive and social-deficit behaviors in mice.
What the researchers did
The researchers focused on a gene called GRIK4, which regulates production of a receptor subunit known as GluK4. When GRIK4 is overexpressed, GluK4 levels rise and animals display anxiety-like traits — avoiding open spaces, reduced social interaction and behaviors resembling depression. Those mice also showed impairments in object-recognition memory.
Using gene-editing techniques to reduce excess copies of GRIK4, the team lowered GluK4 levels in the amygdala. That intervention abolished the anxiety-like, depression-like and social-deficit behaviors in the engineered animals. Similar benefits were observed when the treatment was applied to non-engineered mice that naturally exhibited higher anxiety levels.
“That simple adjustment was enough to reverse anxiety-related and social deficit behaviors, which is remarkable,”
— Álvaro García, neuroscientist involved in the study.
Which neurons matter?
Further analysis identified a discrete neuronal population within the amygdala whose imbalanced activity appears sufficient to trigger pathological anxiety-related behaviors. When the activity of these cells was normalized, the animals' behavior returned to baseline for anxiety and social measures.
Important caveats
Although anxiety-like and social behaviors improved, the treated mice continued to struggle with object-recognition memory in later tests. That suggests reducing GRIK4 expression in this amygdala circuit did not repair all brain systems affected by anxiety-related pathology.
These experiments were performed in mice, which are a well-established model for many aspects of brain function, but the same mechanisms have not yet been directly demonstrated in humans. The authors caution that translating gene-targeting or circuit-level interventions to people will require extensive additional research and safety testing.
Why this matters
The study — published in the journal iScience — highlights that very localized circuit imbalances can drive affective symptoms and that restoring balance in defined neural populations can alleviate them. The findings point toward more targeted therapeutic strategies that aim at specific neural circuits rather than broad-acting drugs.
Bottom line: Manipulating GRIK4 and normalizing activity in a specific group of amygdala neurons reversed anxiety-like and social-deficit behaviors in mice, suggesting a promising direction for future research into localized, circuit-based treatments for affective disorders. However, memory deficits persisted and human relevance remains to be demonstrated.