Specific brain circuit identified for anxiety
Scientists at the Institute for Neurosciences in Alicante, Spain, have identified a specific population of neurons in the brain that, when imbalanced, triggers anxiety and social withdrawal. The research team, led by Professor Juan Lerma, found that hyperexcitable neurons in the basolateral amygdala disrupt communication with regular-firing neurons in the centrolateral amygdala. This disruption alone is enough to cause pathological anxiety behaviors.
The study, published in the journal iScience, used mice genetically engineered to overexpress a gene that makes specific amygdala neurons hyperexcitable. The researchers also tested naturally anxious wild-type mice to confirm the findings applied beyond the specific genetic model.
Restoring balance reverses symptoms
When the researchers restored normal activity to the identified brain circuit, the anxiety-related and social deficit behaviors in the mice reversed. The animals showed reduced anxiety in open-field exploration tests and increased willingness to interact with unfamiliar mice. Lead author Alvaro Garcia called the result remarkable, noting that a simple adjustment was enough to reverse the behavioral changes.
The team used a combination of genetic engineering, modified viruses, electrophysiological recordings, and behavioral testing to map the circuit. They focused on the Grik4 gene, which controls GluK4 glutamate receptors. Normalizing the activity of this gene in the basolateral amygdala restored proper communication with the centrolateral amygdala.
Path toward new anxiety treatments
The discovery opens the door to more targeted treatments for anxiety disorders, depression, and social deficits seen in conditions like autism and schizophrenia. Current treatments often target broad brain systems and can cause side effects. A circuit-specific approach could allow doctors to treat the root cause of anxiety without affecting other brain functions.
Professor Lerma cautioned that the finding is not a complete cure. Memory deficits in the mice did not improve, suggesting other brain regions such as the hippocampus are involved. He said targeting these specific neural circuits could become an effective and more localized strategy to treat affective disorders in humans, though clinical applications remain years away.