Dopamine in the amygdala guides social development in infant rats

The abnormal social behaviors associated with mental disorders often arise in childhood and are closely linked to dysfunctions of neural circuits. The obvious technical limitations of studying neural networks in infants have limited our knowledge of how these neural circuits develop in health and disease.

In a new study of infant rats, researchers at NYU Grossman School of Medicine have shown that deficits in social behaviors seen in psychiatric disorders such as autism are caused by socially stressful experiences in early life. and increased levels of dopamine in a specific nucleus in the amygdala that plays a role in memory formation called the basolateral nucleus. Often referred to as the “feel-good chemical,” dopamine is a hormone and neurotransmitter that plays an important role in the reward mechanisms of the brain.

The results are reported in a journal article neuron, entitled, “Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala.”

Although it is widely accepted that negative experiences in early life affect the social development of species, the mechanisms underlying this impact are unclear. New findings from the current study link repeated stress in early childhood to increased dopamine levels in the basolateral amygdala.

Maya Opendak, PhD, postdoctoral fellow in the Department of Child and Adolescent Psychiatry at NYU Langone Health, is the lead author of the paper.

“This work highlights a particular circuit linking adversity, impaired caregiver treatment and long-lasting social deficits. This may represent one way that adversity initiates an aberrant developmental trajectory associated with amygdala deficits and social behavior, although many others likely coexist,” said Maya Opendak, PhD, postdoctoral fellow in the Department of Psychiatry at Child and Adolescent at NYU. Langone Health and lead author of the article.

To understand the neural circuits involved in the progressive worsening of social behavior, the authors of the new study used a suite of experimental methods in awake rats: optogenetics, microdialysis and microinfusions. The researchers adapted optogenetics to puppies, using light to control the release of dopamine in individual brain cells to test its impact on social behavior following adversity.

To induce maternal harshness towards the pups, researchers provided limited bedding materials in the cage, which decreases the mothers’ ability to build a nest, causing the mother rats to engage in frequent nest building and stepping over their puppies in the process.

Modeling early stress through harsh maternal care or maternal presence during repeated mild shocks to the tail, the researchers found that both paradigms increase dopamine levels in the basolateral amygdala, which is sufficient to trigger abnormal social behavior.

In a series of social behavior tests, the authors measured how long puppies approached their mother or peers after five days of living under these stressful conditions. According to the results, the longer the exposure to stress, the less often the puppies approach their mother.

When the team housed mother rats and their pups under stressful conditions, the pups showed nearly doubled activity in the basolateral amygdala compared to those reared in a comfortable nest. Stressed puppies spent at least 90% less time around their mother and more than 30% less time around other puppies compared to unstressed puppies.

To further confirm their findings, the authors blocked dopamine release in the basolateral amygdala in distressed puppies through pharmaceutical intervention. This restored social behavior to normal. On the other hand, increased dopamine levels in puppies raised under non-stressful conditions impaired their social behavior.

Interestingly, adversity alone, modeled as repeated shocks in the absence of the social component—the presence of a harsh or anesthetized mother rat—did not increase amygdala dopamine levels or cause deficits. social.

“Adversity with the mother, but not adversity alone, was necessary to initiate impairments in dopamine circuitry and social behavior,” Opendak said. She suggested that repeated activation of the basolateral amygdala, known to play a key role in threat learning, prompts infants to associate their mothers with danger.

“These data highlight the unique impact of social adversity as causative in producing mesolimbic dopamine circuit dysfunction and aberrant social behavior,” the authors noted.

“Our results suggest that repeated dopamine release in the basolateral amygdala plays a key role in infant social development,” Opendak said. “As a result, this brain region may be a promising target for understanding or even treating psychiatric disorders that can interfere with social interaction, such as autism, anxiety, and depression.”

Regina Sullivan, PhD, a professor in the Department of Child and Adolescent Psychiatry at NYU Langone, is the study’s lead author.

“Our investigation has given us clearer insight into how specific brain mechanisms link stressful experiences in early childhood to lifelong social behavior problems,” said Regina Sullivan, PhD, professor in the department. of Child and Adolescent Psychiatry at NYU Langone and lead author of the study. “We can take this same approach to explore other areas of brain development, such as memory, learning and threat recognition.”

Social behavior involves a complex network of cells and circuits. In future work, the team intends to study other brain areas involved in threat and reward processing, Sullivan said.

Joel C. Hicks