Stress experienced during adolescence can lead to changes in postpartum social behavior in women and other mammals. Such changes can encompass a variety of alterations, including depression and modified social behavior after childbirth. Yet, the neural circuit mechanisms underpinning these changes are not fully understood.
Investigating the Effects of Stress in Adolescence on Postpartum Social Behavior
In a recent study published in Nature Communications, Minae Niwa, Ph.D., a researcher at the University of Alabama at Birmingham, delved into this complex subject. Niwa leveraged a mouse model and advanced neurobiological techniques to shed light on the impact of adolescent stress on postpartum social behavior. Her work focused on how psychological stress during adolescence changes neuronal functions in the brain, resulting in behavioral modifications after childbirth.
Building on Previous Research: Social Isolation in Adolescence
Niwa’s current research builds on her previous findings, which revealed a fascinating phenomenon: mice exposed to social isolation during late adolescence, even without causing any immediate behavioral or endocrine changes, exhibited long-lasting behavioral shifts postpartum. This occurred only if the social isolation was accompanied by pregnancy and delivery. Together with her team, Niwa utilized this behavioral model to investigate the neural circuit differences postpartum between mice exposed to stress during late adolescence and those that weren’t.
The Role of the Prelimbic Cortex in Social Behavior
Niwa’s research centered on the prelimbic cortex, a critical region of the brain involved in regulating social behavior and stress responses. The researchers applied optogenetics—a technique that uses light signals to selectively activate or inhibit brain circuits—and in vivo calcium imaging, which allows examination of the activity of specific neurons in a brain region. These methods facilitated the understanding of how neurons communicate in freely behaving animals.
Exploring the Impact of Psychosocial Stress on Glutamatergic Pathway
The team from the UAB Department of Psychiatry and Behavioral Neurobiology discovered that adolescent psychosocial stress, along with pregnancy and delivery, resulted in diminished function of a specific brain pathway known as the glutamatergic pathway. This pathway, mapped from the anterior insula region of the brain cortex to the prelimbic cortex, became hypo-functional. Since glutamate is the principal excitatory neurotransmitter in mammals’ central nervous systems, this finding was highly significant.
Social Behavior Changes: Effect of Diminished Cortico-Cortical Pathway Function
The researchers found that the decreased function of the cortico-cortical pathway led to abnormal social behavior. In a test of social novelty, stressed mouse dams displayed a preference for interacting with a familiar mouse over a novel one, unlike unstressed dams.
Role of the Anterior Insula-Prelimbic Cortex Pathway in Recognizing Novelty
Niwa and her team identified the anterior insula-prelimbic cortex pathway as pivotal in recognizing novelty in other mice. They discovered this pathway modulates “stable neurons” in the prelimbic cortex, which are consistently activated or inhibited by novel mice.
Functional Relevance of the Anterior Insula-Prelimbic Cortex Pathway
The UAB researchers conducted experiments demonstrating the functional relevance of the anterior insula-prelimbic cortex pathway. They found decreased activity in this pathway correlated with reduced preference for social novelty in stressed dams. Further, they used optogenetics to reveal that inhibition of this pathway in unstressed dams reduced social interaction with novel mice. Conversely, activation of this pathway in stressed dams improved their social behavior.
Anterior Insula-Prelimbic Cortex Pathway and Social Novelty
Interestingly, the team was able to limit the timing of optogenetic modulation to occur only during mouse exploration or interaction with other mice. Results showed that the anterior insula-prelimbic cortex pathway, which modulates the stable neurons in the prelimbic cortex, plays a crucial role only during social novelty interactions with other mice.
The Involvement of the Glucocorticoid Receptor in Social Behavior Changes
The researchers also uncovered the role of a stress-hormone receptor known as the glucocorticoid receptor (GR) within the anterior insula-prelimbic pathway. By selectively removing the GR in this pathway, they observed a restoration of the changes in neuronal activity in the prelimbic cortex of stressed dams. Niwa indicated, “These findings suggest that the prolonged elevation of the stress hormone during the postpartum period plays a crucial role in the observed alterations in neuronal pathway and social behavior.”
The Implications of the Study on Understanding Postpartum Social Behavior
Niwa concluded, “Our study has revealed significant findings that demonstrate the involvement of the anterior insula-prelimbic pathway in adolescent stress-induced postpartum alterations related to the recognition of the novelty of other mice, which is a key aspect of social behavior.”
She highlighted the importance of further exploration of the anterior insula-prelimbic pathway’s upstream and downstream contributions to better understand postpartum social behavioral changes induced by social isolation in late adolescence, as well as to deepen our understanding of the nature of social behavior.
