How Changes in the Central Amygdala Contribute to Anxiety Disorders

New research reveals how genetic changes in the amygdala circuits can lead to heightened anxiety and fear behaviors, providing insights for targeted mental health treatments.
Researchers at the Max Planck Florida Institute for Neuroscience have uncovered how genetic alterations affecting inhibitory neurons in the brain's amygdala can lead to increased anxiety and fear behaviors. Their study focused on the gene PTEN, which is linked to autism spectrum disorder (ASD) and brain overgrowth. Loss of PTEN in specific inhibitory neurons called somatostatin-expressing cells rewires neural circuits in the central amygdala, a region critical for processing fear and anxiety.
Using advanced circuit-mapping techniques combined with genetic models, the team discovered that deleting PTEN in these inhibitory neurons reduces local inhibitory connectivity by about 50%. This disruption weakens the inhibitory control within the amygdala and enhances excitatory signals from the basolateral amygdala, which delivers emotion-related sensory input. The resulting imbalance correlates with heightened anxiety and fear learning in animal models, while social and repetitive behaviors remain unaffected.
These findings, published in Frontiers in Cellular Neuroscience, shed light on how specific microcircuit changes contribute to anxiety traits in neurodevelopmental disorders. Importantly, the altered neural circuitry does not impact social interactions, suggesting distinct circuit mechanisms underlie different ASD behaviors.
Understanding how PTEN and similar genetic factors modify brain circuits offers promising avenues for targeted therapies aimed at alleviating anxiety and fear-related symptoms. Future research may explore whether these microcircuit alterations are common across various genetic forms of autism and related conditions, paving the way for precision medicine approaches in neurology and psychiatry.
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