Summary: Adolescent stress alters brain functions, influencing postnatal social behavior in mammals.
The study used optogenetics and calcium imaging techniques to understand neural communication in mice that experienced psychosocial stress during adolescence. This stress, combined with pregnancy and childbirth, has been found to affect the function of the glutamatergic pathway, leading to changes in social behavior.
The findings suggest that the stress hormone receptor (glucocorticoid receptor) within this pathway plays a critical role in these changes.
Key facts:
- Adolescent psychosocial stress can alter neural functions in the brain, leading to changes in postnatal social behavior in mammals.
- The research found a reduction in the functionality of a cortico-cortical pathway – the anterior insula-prelimbic cortex pathway – as a result of adolescent stress and subsequent pregnancy, leading to abnormal social behaviour.
- The involvement of a stress hormone receptor known as the glucocorticoid receptor in this pathway suggests the critical role of the stress hormone in behavioral changes after birth.
source: University of Alabama at Birmingham
Stress during adolescence can cause postpartum behavioral changes in women and other mammals, including depression and changes in social behavior after childbirth.
However, the neural circuit mechanisms by which adolescent stress leads to later changes in social behavior after birth are unclear.
IN Nature Communications University of Alabama at Birmingham researcher Minae Niwa, Ph.D., used a mouse model and cutting-edge neurobiological techniques to show how psychological stress during adolescence alters neural functions in the brain, leading to altered social behavior after birth.
This research builds on her recent discovery that mice exposed to social isolation in late adolescence, which itself does not cause endocrine or behavioral changes, show long-lasting behavioral changes only when accompanied by pregnancy and parturition. Credit: Neuroscience NewsThis research builds on her recent discovery that mice exposed to social isolation in late adolescence, which itself does not cause endocrine or behavioral changes, show long-lasting behavioral changes only when accompanied by pregnancy and parturition.
Niwa and his colleagues were able to use this behavioral model to examine differences in neural circuits after birth between mouse mothers who were stressed in late adolescence and a control group of mouse mothers who remained stress-free in adolescence due to normal social interactions with other mice.
Niwa focuses on the prelimbic cortex, an area of the brain that plays a crucial role in social behavior and regulating stress responses. UAB researchers used optogenetics — where light signals can selectively activate or inhibit brain circuits — and Live calcium imaging, which allows researchers to examine the neural activity of specific neurons in a brain region.
These approaches allow researchers to understand how nerve cells communicate in freely behaving animals.
Researchers from UAB’s Department of Psychiatry and Behavioral Neurobiology found that adolescent psychosocial stress combined with pregnancy and childbirth caused hypofunction in the glutamatergic pathway, which they mapped from the anterior insula region of the cerebral cortex to the prelimbic cortex. Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system.
Reduced function of this cortico-cortical pathway alters neuronal activity in the prelimbic cortex and in turn leads to abnormal social behavior, as seen in a test of how much time a dam mouse spends with a familiar mouse that is confined to one corner of a cage, versus a new mouse confined in another corner.
In this social novelty study, nonstressed mothers—as opposed to stressed mothers—spend more time interacting per visit and more total time interacting with the novel mouse.
Specifically, Niwa and colleagues found that the anterior insula-prelimbic cortex pathway plays a critical role in the recognition of the novelty of other mice by modulating what they call “stable neurons” in the prelimbic cortex, which are constantly activated or inhibited by new mice.
A cortico-cortical pathway means that an action potential from a neuron in one area of the cerebral cortex travels to target neurons in another cortical area.
In their first experiments, the UAB researchers found that reduced activity in the anterior insula-prelimbic cortex pathway correlated with reduced social novelty preference in stressed dams. They then used optogenetics to confirm the functional significance of this pathway.
Notably, in social novelty studies, optogenetic inhibition of the anterior insula-prelimbic pathway in unstressed dams reduced social interaction with novel mice, making their social behavior more like stressed dams.
In contrast, optogenetic activation of the anterior insula-prelimbic pathway in stressed dams ameliorates behavioral changes seen in the social novelty test, causing them to act more like non-stressed dams.
Additionally, the UAB team was able to time-limit the optogenetic modulation in the social novelty trials so that it occurred only during cage exploration with the mouse or only during interaction with the novel or familiar mice, which were limited to two cell corner.
The results indicate that the anterior insula-prelimbic cortex pathway, which modulates stable neurons in the prelimbic cortex, plays a crucial role only during social novelty interactions with other mice and not during exploration.
Additionally, they revealed the involvement of a stress hormone receptor called the glucocorticoid receptor, or GR, in the anterior insula-prelimbic pathway. By selectively ablating GR in this pathway, they observed a restoration of changes in neuronal activity in the prelimbic cortex of stressed dams.
“These findings suggest that the sustained increase in stress hormone during the postpartum period plays a critical role in the observed changes in neural pathway and social behavior,” Niva said.
“Our study revealed significant findings that demonstrate the involvement of the anterior insula-prelimbic pathway in adolescent stress-induced postnatal changes related to recognition of the novelty of other mice, a key aspect of social behavior,” she said.
“Investigating the upstream and downstream contributions of the anterior insula-prelimbic pathway would facilitate our understanding of the postnatal changes in social behavior that are induced by social isolation in late adolescence, as well as our understanding of the nature of social behavior.”
Co-authors with Niwa on the study, “Adolescent stress impairs postnatal social behavior via the anterior insula-prelimbic pathway in mice” are Kyohei Kin, Jose Francis-Oliveira and Shin-ichi Kano. All are in the UAB Department of Psychiatry and Behavioral Neurobiology, where Niva is an associate professor. Psychiatry and Behavioral Neurobiology is a department in the Marnix E. Heersink School of Medicine.
Financing: Support came from National Institutes of Health grants MH116869 and MH128708; UAB Psychiatry and Behavioral Neurobiology Seed Funds; and the Takeda Science Foundation Scholarship Program for Young Japanese Doctors and Doctors Studying Abroad.
About this news about stress research and social neuroscience
Author: Jeffrey Hansen
source: University of Alabama at Birmingham
Contact: Jeffrey Hansen – University of Alabama at Birmingham
Image: Image credit: Neuroscience News
Original research: Free access.
“Adolescent stress impairs postnatal social behavior through the anterior insula-prelimbic pathway in mice” by Mina Niva and others. Nature Communications
Summary
Adolescent stress impairs postnatal social behavior through the anterior insula-prelimbic pathway in mice
Adolescent stress may be a risk factor for abnormal social behavior in the postpartum period, which critically affects individual social functioning. Nevertheless, the underlying mechanisms remain unclear.
Using a mouse model with optogenetics and in vivo calcium imaging, we found that adolescent psychosocial stress combined with pregnancy and childbirth causes hypofunction of the glutamatergic pathway from the anterior insula to the prelimbic cortex (AI-PrL pathway), which alters PrL neuronal activity. and in turn led to abnormal social behavior.
Specifically, the AI-PrL pathway played a critical role in the novelty recognition of other mice by modulating “stable neurons” in the PrL that were persistently activated or inhibited by novel mice. We also observed that glucocorticoid receptor signaling in the AI-PrL pathway has a causal role in stress-induced postpartum changes.
Our findings provide functional insight into a cortico-cortical pathway underlying adolescent stress-induced postnatal social behavioral deficits.