A tiny circuit in the amygdala is getting a lot of attention from researchers in Spain.
Scientists led by Juan Lerma at the Synaptic Physiology laboratory at the Institute for Neurosciences, a joint centre of the Spanish National Research Council and Miguel Hernández University of Elche, say they have identified a specific brain circuit that appears to play a major role in anxiety, depression-like behaviours and social withdrawal in mice.
Their findings were published in iScience.
The study focused on the amygdala, a brain region involved in emotions such as fear and anxiety. The researchers identified a particular group of neurons in this area that had a strong effect on emotional and social behaviour.
“We already knew the amygdala was involved in anxiety and fear, but now we’ve identified a specific population of neurons whose imbalanced activity alone is sufficient to trigger pathological behaviors,” Lerma said.
To study the circuit, the team used genetically engineered mice that produced unusually high levels of the Grik4 gene. That increased the number of GluK4 glutamate receptors and made certain neurons more excitable than normal.
The mouse model was first developed by the same laboratory in 2015. The animals show behaviours resembling anxiety and social withdrawal, traits the researchers said are often associated with conditions such as autism and schizophrenia.
The scientists then targeted neurons in the basolateral amygdala. By normalising Grik4 gene activity in that region, they restored communication with inhibitory neurons in the centrolateral amygdala known as regular firing neurons.
“That simple adjustment was enough to reverse anxiety-related and social deficit behaviors, which is remarkable,” said Álvaro García, the study’s first author.
The team used electrophysiological recordings and behavioural tests commonly used to assess anxiety, depression and social interaction in rodents. The tests looked at behaviours including willingness to explore open spaces and interest in unfamiliar mice.
Using genetic engineering techniques and modified viruses, the researchers selectively corrected the neural imbalance in the basolateral amygdala. They then recorded improvements in brain activity and behaviour.
The team also tested the same intervention in wild-type mice that naturally showed elevated anxiety levels. The treatment reduced anxiety in those animals too.
“This validates our findings and gives us confidence that the mechanism we identified is not exclusive to a specific genetic model, but may represent a general principle for how these emotions are regulated in the brain,” Lerma said.
Not every symptom changed after the intervention. The mice still showed deficits in object recognition memory, which the researchers said suggests other brain regions may be involved, including the hippocampus.
“Targeting these specific neural circuits could become an effective and more localized strategy to treat affective disorders,” the researcher said.
The study was funded by the Spanish State Research Agency, the Spanish Ministry of Science, Innovation and Universities, the Severo Ochoa Excellence Program for Research Centers at the Institute for Neurosciences CSIC-UMH, the European Regional Development Fund, and the Generalitat Valenciana through the PROMETEO and CIPROM programs.
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