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Understanding Stress Responses in Animals

This article covers how stress affects behavior in animals and the role of the CA2 region.

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Stress is a common experience that can affect many animals, including humans. When faced with danger or threats, animals often respond in ways that help them survive. This response is called the acute stress response, and it helps animals learn and adapt to their environments. However, not every animal reacts the same way to stress. Some animals may show signs of lasting stress, while others seem to cope better.

In humans, a traumatic event can lead to conditions like post-traumatic stress disorder (PTSD), which affects mood and behavior in various ways. Interestingly, not everyone who goes through trauma develops PTSD. Similarly, in studies with mice, some animals that experience repeated stress from aggressive encounters develop avoidance Behaviors, while others do not. This variability raises questions about what makes some individuals more prone to stress-related issues than others.

The Role of the Hippocampus

The hippocampus is an important brain region involved in memory and stress responses. Within the hippocampus, there are different areas that play distinct roles. One such area, called CA2, is involved in recognizing Social situations and forming relationships. It helps animals remember familiar companions and identify potential threats.

Research has shown that the activity of CA2 is linked to various behaviors. For instance, it influences how aggressive an animal is towards others and helps in remembering fear in certain contexts. Moreover, CA2 contains a high number of receptors sensitive to stress hormones, which suggests it plays a significant role in how animals process stressful situations.

Effects of Social Stress

Studies have used a method called chronic social defeat stress (CSDS) in mice, where they are exposed to Aggression repeatedly over days. Some mice become socially avoidant after this experience, while others show few signs of stress. Those that are more sensitive to stress often display long-lasting changes in their brains. These changes can affect behaviors and brain regions associated with stress and aggression.

When mice are placed in the presence of an aggressor, those who show defensive behaviors may be more likely to cope well with stress. In contrast, others that display submissive or fearful responses might struggle more in social situations. Research aims to understand these differences to uncover the underlying mechanisms of stress response.

Understanding Stress Resilience and Susceptibility

Scientists have been studying the differences between animals that thrive despite stress and those that struggle. This research involves looking at physical and behavioral responses after stressful events. For example, assessing how mice react during and after a stressful encounter can reveal valuable information.

One focus has been on the different brain structures and their roles in predictive behaviors. In particular, there is interest in the role of the CA2 region of the hippocampus. The goal is to see if its activity can help predict which animals will behave resiliently and which will be more susceptible to stress-related problems.

Investigating CA2's Role in Stress Responses

The recent studies have shown that area CA2 is crucial for understanding how animals process social stress. This area not only helps with aggression but also plays a role in how animals form social bonds. It was hypothesized that manipulating the activity of CA2 could change how animals respond to stress.

To investigate this, researchers used genetically modified mice that allowed them to inhibit CA2 activity during social stress tests. By comparing these modified mice to normal ones, they could assess how changes in CA2 activity affected later behaviors after a stressful encounter.

The Acute Social Defeat Model

In an acute social defeat (aSD) model, mice are briefly exposed to an aggressive mouse. Following this interaction, their behavior is observed in a new environment filled with potential social triggers. Researchers noted that defeated mice tended to avoid social interactions, spending more time away from the area where the aggressor was located.

Over time, it was observed that the behaviors of these mice remained influenced by their initial defeat. In some cases, the avoidant responses persisted long after the encounter, indicating how a brief stressful experience could have lasting effects on behavior.

Behavioral Analysis of Social Avoidance

The behavioral assays employed in these studies allowed researchers to quantify how much time the defeated mice spent exploring or avoiding certain areas. Avoidance was measured by tracking how long the mice stayed away from an area containing a familiar aggressor compared to controls.

These observations revealed a clear difference in behavior. Defeated mice spent significantly more time in areas of the arena furthest from the aggressor compared to non-defeated controls. This demonstrated that the experience of social defeat influenced their willingness to engage socially even days after the event.

Impact of CA2 on Social Behavior

Given the established role of CA2 in social processing, researchers were interested in how manipulating this area's activity might influence social behaviors. Using chemogenetic techniques, they inhibited CA2 during the defeat sessions. Surprisingly, these mice showed even greater avoidance behavior than those with normal CA2 activity. This suggested that active CA2 during the defeat might help moderate stress responses and encourage investigative behavior in these encounters.

The findings indicated that the activity in CA2 could be a key factor in how animals process threatening situations and engage with potential social partners. This reinforces the notion that the brain's response to stress is complex and involves multiple regions interacting with one another.

Mechanisms of Stress Resilience

The results emphasize the need to understand how resilience to stress develops. It appears that experiences during a stressful situation can shape future behaviors. Those mice that showed more defensive behaviors during the defeat were also more likely to explore their environment later on.

In contrast, those exhibiting submissive behaviors tended to show higher levels of avoidance afterward. These patterns highlight the critical role of behavioral responses during stress in determining how animals cope in the long term.

Effects on Corticolimbic Brain Regions

The next step was to explore how the activity in CA2 affects other brain regions involved in processing stress and social information. Specifically, researchers examined connections between CA2 and areas such as the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC).

Using techniques to stimulate CA2 neurons, they observed increased activity in both mPFC and ACC. This indicates that information from CA2 is likely transmitted to these higher brain regions, influencing decision-making and emotional responses. When CA2 activity was inhibited, damage to these neural pathways could lead to changes in how mice engaged with their environment, further underscoring the importance of CA2 in stress processing.

Discussion on Findings

Overall, these findings suggest that the way animals respond to an immediate stressor can have profound consequences on their behavior in the future. By understanding this relationship, researchers can start to untangle the complexities of stress responses and resilience. The interplay between different brain regions and their roles in processing social interactions can help to develop better strategies to support those affected by stress-related disorders.

The specific focus on CA2 contributes to the growing body of literature addressing the functionality of various brain structures in stress responses. Future studies will likely continue to explore how modifying these responses might help improve behavioral outcomes following stressful experiences.

Conclusion

In summary, the relationship between stress responses and behavior is intricate and multi-faceted. Research into areas like CA2 provides valuable insights into the mechanisms that underlie resilience and susceptibility to stress. By continuing to study these relationships, we can better understand how to support those affected by stress and promote healthier coping strategies in both animals and humans.

Original Source

Title: Hippocampal area CA2 activity supports social investigation following an acute social stress.

Abstract: Neuronal activity in the hippocampus is critical for many types of memory acquisition and retrieval and influences an animals response to stress. Moreover, the molecularly distinct principal neurons of hippocampal area CA2 are required for social recognition memory and aggression in mice. To interrogate the effects of stress on CA2-dependent behaviors, we chemogenetically manipulated neuronal activity in vivo during an acute, socially derived stressor and tested whether memory for the defeat was influenced. One day after an acute social defeat (aSD), defeated mice spent significantly less time investigating another mouse when compared to non-defeated control mice. We found that this avoidant phenotype persisted for up to one month following a single defeat encounter. When CA2 pyramidal neuron activity was inhibited with Gi-DREADD receptors during the defeat, subject mice exhibited a significantly higher amount of social avoidance one day later when compared to defeated littermates not expressing DREADDs. Moreover, CA2 inhibition during defeat caused a reduction in submissive defense behaviors in response to aggression. In vitro electrophysiology and tracing experiments revealed a circuit wherein CA2 neurons connect to caudal CA1 projection neurons that, in turn, project to corticolimbic regions including the anterior cingulate cortex. Finally, socially avoidant, defeated mice exhibited significant reductions in cFos expression in caudal hippocampal and limbic brain areas during a social investigation task 24 hours after aSD. Taken together, these results indicate that CA2 neuronal activity is required to support behavioral resilience following an acute social stressor and that submissive defensive behavior during the defeat (vs. fleeing) is a predictor of future resilience to social stress. Furthermore, CA2 preferentially targets a population of caudal CA1 projection neurons that contact cortical brain regions where activity is modulated by an acute social stressor.

Authors: Serena M. Dudek, D. Radzicki, K. E. E. McCann, G. M. Alexander

Last Update: 2024-02-15 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.02.14.580182

Source PDF: https://www.biorxiv.org/content/10.1101/2024.02.14.580182.full.pdf

Licence: https://creativecommons.org/licenses/by/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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