Summary: Stress during adolescence impairs brain function, influencing postpartum social behavior in mammals.
The research uses optogenetics and calcium imaging techniques to understand neural communication in mice that experienced psychosocial stress during adolescence. He found that this stress, combined with pregnancy and childbirth, impacts the function of the glutamatergic pathway, leading to changes in social behavior.
The results suggest that a stress hormone receptor (glucocorticoid receptor) in this pathway plays a crucial role in these alterations.
- Psychosocial stress in adolescents can alter neural functions in the brain, leading to changes in postpartum social behavior in mammals.
- Research has shown decreased functionality of a cortico-cortical pathway – the anterior insula-prelimbic cortex pathway – due to adolescent stress and subsequent pregnancy, leading to abnormal social behavior .
- The involvement of a stress hormone receptor, known as the glucocorticoid receptor, in this pathway suggests the critical role of stress hormone in postpartum behavioral changes.
Source: University of Alabama at Birmingham
Stress during adolescence can lead to postpartum behavior changes in females and other mammals, including depression and changes in social behavior after the birth of a child.
However, the neural circuit mechanisms by which adolescent stress drives subsequent changes in postpartum social behavior are unclear.
In a Nature Communication study, University of Alabama at Birmingham researcher Minae Niwa, Ph.D., used a mouse model and state-of-the-art neurobiological techniques to show how psychological stress during adolescence alters neural functions in the brain, resulting in a altered postpartum social behavior.
This research builds on his recent finding that mice exposed to social isolation in late adolescence, which alone does not cause any endocrine or behavioral changes, show lasting behavioral changes only when they are accompanied by pregnancy and childbirth.
Niwa and colleagues were able to use this behavioral model to probe postpartum neural circuitry differences between mothers of mice stressed in late adolescence and a control group of mothers of mice who remained unstressed through adolescence. , due to normal social interactions with other mice.
Niwa focused on the prelimbic cortex, a central region of the brain that plays a crucial role in social behavior and regulating stress responses. The 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 region of the brain.
These approaches allow researchers to understand how nerve cells communicate in free-behaving animals.
Researchers from UAB’s Department of Psychiatry and Behavioral Neurobiology found that psychosocial stress in adolescents, combined with pregnancy and childbirth, caused hypofunction of the glutamatergic pathway which they mapped from the anterior insular region from the cerebral cortex to the prelimbic cortex. Glutamate is the main excitatory neurotransmitter in the mammalian central nervous system.
Decreased function of this cortico-cortical pathway impaired neural activity in the prelimbic cortex and led, in turn, to abnormal social behavior, as shown by a test of how long a mother mouse spends with a familiar mouse which is confined to a corner. of a cage, against a new mouse, confined in another corner.
In this social novelty trial, unstressed mothers—unlike stressed mothers—spent more interaction time per visit and more total interaction time with the novel mouse.
Specifically, Niwa and colleagues found that the anterior insula-prelimbic cortex pathway plays a crucial role during novelty recognition of other mice by modulating what they call “stable neurons” in the prelimbic cortex, that were constantly activated or inhibited by new mice.
A cortico-cortical pathway means that the 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 decreased activity in the anterior pathway of the insula-prelimbic cortex correlated with a reduced preference for social novelty in stressed mothers. They then used optogenetics to confirm the functional relevance of this pathway.
Notably, in social novelty trials, optogenetic inhibition of the anterior insula-prelimbic pathway in unstressed mothers reduced social interaction with novel mice, making their social behavior more like that of stressed mothers.
In contrast, optogenetic activation of the anterior insula-prelimbic pathway in stressed mothers enhanced the behavioral changes seen in the social novelty trial, making them act more like unstressed mothers.
Additionally, the UAB team was able to restrict the timing of optogenetic modulation in the social novelty trials so that it only occurred during the mouse’s exploration of its cage or only during the mouse’s cage exploration. interacting with new or familiar mice that were constrained to two corners of the cage.
The results showed that the anterior insula-prelimbic cortex pathway that modulates stable neurons in the prelimbic cortex plays a crucial role only during social novelty interactions with other mice, rather than 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 suppressing the GR in this pathway, they observed a restoration of neuronal activity changes in the prelimbic cortex of stressed mothers.
“These findings suggest that prolonged stress hormone elevation during the postpartum period plays a crucial role in the observed alterations in neural pathway and social behavior,” Niwa said.
“Our study revealed significant results that demonstrate the involvement of the anterior insula-prelimbic pathway in stress-induced postpartum alterations in adolescents related to recognition of novelty from other mice, which is a key aspect social behavior,” she said.
“Exploring the upstream and downstream contributions of the anterior insula-prelimbic pathway would aid our understanding of postpartum social behavior changes induced by social isolation in late adolescence, as well as our understanding of the nature social behavior.”
Co-authors with Niwa in the study, “Adolescence stress impairs postpartum social behavior via the anterior insula-prelimbic pathway in mice,” are Kyohei Kin, Jose Francis-Oliveira, and Shin-ichi Kano . All are part of UAB’s Department of Psychiatry and Behavioral Neurobiology, where Niwa is an associate professor. Psychiatry and Behavioral Neurobiology is a department of the Marnix E. Heersink School of Medicine.
Funding: Support came from National Institutes of Health grants MH116869 and MH128708; UAB Psychiatry and Behavioral Neurobiology Startup Fund; and the Takeda Science Foundation Fellowship Program for Young Japanese Physicians and Doctors Studying Abroad.
About this stress and social neuroscience research news
Author: Jeffrey Hansen
Source: University of Alabama at Birmingham
Contact: Jeffrey Hansen – University of Alabama at Birmingham
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Adolescence stress impairs postpartum social behavior via the anterior insula-prelimbic pathway in mice” by Minae Niwa et al. Nature Communication
Adolescent stress impairs postpartum social behavior via 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. However, 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, caused hypofunction of the insula glutamatergic pathway. anterior to the prelimbic cortex (AI-PrL pathway), which altered PrL neuronal activity. , and in turn leads to abnormal social behavior.
Specifically, the AI-PrL pathway played a crucial role during the recognition of novelty from other mice by modulating “stable neurons” in PrL, which were constantly activated or inhibited by new mice. We also observed that glucocorticoid receptor signaling in the AI-PrL pathway had a causal role in stress-induced postpartum changes.
Our results provide functional insights into a cortico-cortical pathway underlying stress-induced postpartum social behavioral deficits in adolescents.