New Research Reveals Brain Mechanism Behind Anxiety Disorders

A research team at the Institute for Neurosciences, led by Juan Lerma, has revealed that a specific group of neurons in the amygdala plays a critical role in anxiety, depression, and social behavior changes.

This groundbreaking study, published in iScience, indicates that restoring the balance of neuronal excitability within the amygdala can reverse anxiety-related behaviors in mice. Lerma notes that previous knowledge of the amygdala's involvement in anxiety has now been expanded by identifying a particular population of neurons whose imbalanced activity can trigger pathological behaviors.

The team utilized genetically modified mice that overexpress the Grik4 gene, which enhances the production of GluK4-type glutamate receptors, leading to heightened neuronal excitability. These mice exhibited anxiety and social withdrawal akin to symptoms seen in autism and schizophrenia.

By normalizing the Grik4 expression in neurons of the basolateral amygdala, researchers successfully reestablished normal communication with a subset of inhibitory neurons in the centrolateral amygdala, known as regular firing neurons.

Alvaro Garcia, the study's first author, emphasizes that this adjustment was sufficient to reverse anxiety-related and social deficit behaviors, marking a significant finding in the field. The researchers employed electrophysiological recordings and behavioral tests to evaluate anxiety, depression, and social interactions.

These assessments measured traits such as preference for open versus enclosed spaces and interest in unfamiliar mice. The study further applied the same treatment approach to wild-type mice, which are not genetically modified but naturally display elevated anxiety levels.

The results confirmed that the identified mechanism is broadly applicable and not limited to a specific genetic model. Lerma expresses optimism, stating that targeting these neural circuits could lead to effective localized treatments for affective disorders.

However, the research did reveal that some cognitive deficits, such as object recognition memory issues, remained uncorrected, indicating that other brain regions, like the hippocampus, may also play a role in these disorders.

This research was supported by various Spanish governmental and regional programs, highlighting its importance in advancing mental health treatment methodologies. The implications of this study could pave the way for innovative therapies aimed specifically at anxiety disorders.