Summary: New rodent research suggests that repeated dopamine release in the basolateral amygdala (BLA) during stressful experiences in infancy can produce long-lasting changes in social behavior.
Source: NYU Langone
Researchers at NYU Grossman School of Medicine report that shifts in dopamine signaling — a neurotransmitter tied to motivation and reward — may help explain how early-life stress leads to persistent social difficulties.
Previous work has shown that adverse conditions in early life alter social development across mammals, including humans. For example, studies in rats have demonstrated that limiting bedding material causes maternal rough handling of pups and produces lasting changes in offspring social behavior. What remained unclear was which brain mechanisms translate those early stressful experiences into lifelong behavioral differences.
In a study led by investigators at NYU Grossman, the team linked repeated stress during infancy with elevated dopamine levels in the basolateral amygdala (BLA), a brain region central to learning and memory formation. When mother rats and their litters were raised in experimentally induced stressful conditions, the pups showed roughly double the BLA activity measured in pups reared in comfortable nests.
Those increased BLA responses corresponded with pronounced social changes: stressed pups spent at least 90 percent less time near their mothers and more than 30 percent less time near other pups compared with nonstressed controls. The findings indicate a strong association between heightened dopamine signaling in the BLA during infancy and reduced social engagement later in development.
“Our findings suggest that repeated dopamine release in the basolateral amygdala plays a key role in infant social development,” says study lead author Maya Opendak, PhD. “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.”
To probe causality, the team used pharmacological and optogenetic approaches. Blocking dopamine release in the BLA of stressed pups restored normal social behavior, while experimentally increasing dopamine signaling in pups raised under non-stressful conditions produced social impairments. These manipulations indicate that dopamine activity in the BLA is not merely correlated with, but can drive, changes in social behavior after early-life stress.
Importantly, elevated BLA activity and social impairment emerged only when pups experienced stress in their mother’s presence; pups exposed to stress alone did not develop these changes. Opendak and colleagues interpret this pattern to mean that repeated activation of BLA circuits — which are known to participate in learning about threats — leads infants to form associations linking their mother with danger.
“Our investigation offered a clearer view of how specific brain mechanisms link stressful experiences during infancy to lifelong social behavior problems,” says study senior author Regina Sullivan, PhD. “This approach can also be applied to study other aspects of brain development, including memory, learning, and threat recognition.”
The research appeared online Oct. 26 in the journal Neuron. The team assessed the behavior of hundreds of rat pups. Some mothers were given limited nesting materials to create a stressful rearing environment. After five days in these conditions, the researchers measured how often pups approached their mothers and peers. They found a clear relationship: the longer the pups were exposed to the stressful rearing environment, the less frequently they sought proximity with their mothers.
Methodologically, the investigators combined behavioral assays with pharmacological blockade of dopamine release and optogenetic stimulation of individual dopamine-releasing cells in the BLA to determine the chemical’s causal impact on social behavior after early distress.
Sullivan emphasizes that the work examined a single neurotransmitter pathway and that social behavior arises from a complex network of brain circuits. Future research by the team will explore additional brain regions that process threat and reward, aiming to map the broader circuitry that underlies social development following early stress.
Funding: This study was supported by National Institutes of Health grants K99 MH124434, F32 MH112232, R37 HD083217, and R01 AA02381, and by the Brain & Behavior Research Foundation.
Authors and contributors from NYU Langone include Maya Opendak, PhD; Regina Sullivan, PhD; Rosemarie Perry, PhD; Katherine Packard, MS; Shannon Hu, BA; Roseanna Zanca, PhD; Soomin Song, PhD; Robert Froemke, PhD; Joyce Woo, BA; Krissian Martinez, BA; Yaragudri Vinod, PhD; and Donald Wilson, PhD. Additional collaborators are Charlis Raineki, PhD (Brock University); Millie Rincon-Cortes, PhD (University of Pittsburgh); Emma Wood, BA (Nathan Kline Institute); Roseanna Zanca, BA; Peter Serrano, PhD (CUNY Hunter College); Russell Brown, PhD; and Gerald Deehan, PhD (East Tennessee State University).
About this neurodevelopment research news
Author: Shira Polan
Source: NYU Langone
Contact: Shira Polan – NYU Langone
Image: The image is in the public domain
Original Research: The findings are published in Neuron.