Scientists Reverse Anxiety by Targeting Amygdala Neurons

A research team at the Institute for Neurosciences has made significant strides in understanding anxiety by targeting specific neurons in the amygdala, a critical area for emotion processing. According to the study published in iScience, the researchers, led by Juan Lerma, discovered a distinct group of neurons whose imbalanced activity can trigger anxiety, depression, and alterations in social behavior.

Lerma explains that previous knowledge about the amygdala's role in anxiety has now been expanded by identifying a specific population of neurons that influence pathological behaviors. The team utilized a genetically modified mouse model that overexpresses the Grik4 gene, leading to an increase in GluK4-type glutamate receptors and heightened neuronal excitability.

This genetic modification resulted in mice exhibiting anxiety and social withdrawal akin to symptoms seen in autism or schizophrenia. By normalizing Grik4 expression in the basolateral amygdala, the researchers were able to restore normal communication with inhibitory neurons in the centrolateral amygdala, referred to as regular firing neurons.

Remarkably, this simple adjustment reversed anxiety-related and social deficit behaviors, as noted by Alvaro Garcia, the first author of the study. The team's evaluation methods included electrophysiological recordings and behavioral tests that assessed anxiety, depression, and social interaction through preferences for open or enclosed spaces and reactions to unfamiliar mice.

The research team then extended their findings to normal, or wild-type mice, which also showed higher anxiety levels, confirming that their approach could effectively reduce anxiety in non-genetically modified models.

This broader applicability suggests that the identified mechanism likely represents a general principle for emotional regulation in the brain, as stated by Lerma. However, it's noted that some cognitive deficits, specifically issues with object recognition memory, were not corrected, indicating the involvement of other brain regions like the hippocampus in these disorders.

These findings illuminate promising new therapeutic avenues, proposing that targeting these specific neural circuits could lead to more effective localized treatments for affective disorders. The study received support from various institutions, including the Spanish State Research Agency and the European Regional Development Fund.