Abnormal social behaviors linked to mental disorders often arise in childhood and are closely linked to dysfunctions in neural circuits. 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 on infant rats, researchers at NYU Grossman School of Medicine showed deficits in social behaviors seen in psychiatric disorders such as autism, are caused by socially stressful experiences in early life and increased dopamine levels in a specific nucleus of the amygdala that plays a role in memory formation called the basolateral nucleus. Often dubbed the “feel-good chemical,” dopamine is a hormone and neurotransmitter that plays an important role in the brain’s reward mechanisms.
The findings are reported in an article in the journal Neuron, titled, “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 social development across species, the mechanisms underlying this impact have been unclear. The new findings in the current study link repeated stress during infancy to increased dopamine levels in the basolateral amygdala.
“This work provides evidence for a specific circuit linking adversity, altered processing of the caregiver, and lasting social deficits. This may represent one way in which adversity initiates an aberrant developmental trajectory associated with amygdalar deficits and social behavior, although many others are likely to coexist,” said Maya Opendak, PhD, a postdoctoral research fellow in the department of child and adolescent psychiatry at NYU Langone Health, and lead author of the paper.
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, infant rats: optogenetics, microdialysis, and microinfusions. The researchers adapted optogenetics for pups, using light to control dopamine release in individual brain cells to test its impact on social behavior following adversity.
To induce maternal harshness toward pups, the researchers provided limited bedding materials in the cage which decreases the mothers’ ability to construct a nest, causing mother rats to engage in frequent nest building, and step over their pups in the process.
Modeling early-life stress through harsh maternal care or maternal presence during repeated mild shock to the tail, the researchers uncovered that both paradigms increase dopamine levels in the basolateral amygdala, which is enough to trigger abnormal social behavior.
In a series of social behavior tests, the authors measured the duration for which pups approach their mothers or peers after five days of living in these stressful conditions. According to the findings, the longer the stress exposure, the less often pups approach their mothers.
When the team housed mother rats and their pups in stressful conditions, the pups showed almost a two-fold increase in activity in the basolateral amygdala compared with those raised in a comfortable nest. Stressed pups spent at least 90% less time near their mothers and over 30% less time near other pups compared with the unstressed pups.
To further confirm their findings, the authors blocked dopamine release in the basolateral amygdala in the distressed pups through pharmaceutical intervention. This restored the social behavior to normal. On the other hand, increasing dopamine levels in pups raised in nonstressful 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 raise dopamine levels in the amygdala or cause social deficits.
“Adversity with the mother, but not adversity alone, was necessary for initiating impairments in dopamine circuitry and social behavior,” said Opendak. She suggested that the repeated activation of the basolateral amygdala, known to play a key role in learning about threats, prompts infants to associate their mother with danger.
“These data highlight the unique impact of social adversity as causal in producing mesolimbic dopamine circuit dysfunction and aberrant social behavior,” the authors noted.
“Our findings suggest that repeated dopamine release in the basolateral amygdala plays a key role in infant social development,” said Opendak. “As a result, this region of the brain may be a promising target for understanding or even treating psychiatric disorders that can interfere with social interaction, such as autism, anxiety, and depression.”
“Our investigation offered us a clearer look at how specific brain mechanisms link stressful experiences during infancy to lifelong social behavior problems,” said Regina Sullivan, PhD, professor in the department of child and adolescent psychiatry at NYU Langone and senior author on 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 an intricate network of cells and circuits. In future work, the team intends to investigate other brain areas involved in processing threat and reward, said Sullivan.
