Effects of Repeated Social Stress on Neuronal Activity in the Posterior Medial Amygdala of Male Rats

Background

Social stress plays a crucial role in social behavior and mental health. Chronic social stress not only leads to changes in individual behavior but is also closely related to the development of various psychiatric disorders, such as anxiety and depression. The medial amygdala (MeA), a key region in the brain for processing social information, is involved in regulating a range of social behaviors, including aggression, territoriality, mating, and maternal behaviors. However, the specific mechanisms by which social stress affects the activity of MeA neurons remain poorly understood.

Previous studies have shown that the MeA plays an important role in social behavior, but its response mechanisms to social stress are still unclear. In particular, the posterior medial amygdala (MeAP) and its subnuclei (e.g., the posterodorsal subnucleus MeAPd) are significantly involved in social engagement. Additionally, the MeAP has strong connections with several brain regions involved in social functions, such as the posterior bed nucleus of the stria terminalis (pBNST) and the ventromedial hypothalamus (VMH). Therefore, investigating the effects of social stress on MeAP neuronal activity can help reveal how stress alters social behavior and provide new insights into social dysfunction in psychiatric disorders.

This study was conducted by Alexandra C. Ritger and her team at Rosalind Franklin University and was published on January 7, 2025, in the Journal of Neurophysiology.

Research Process and Experimental Methods

Experimental Subjects and Grouping

The study used adult male Sprague-Dawley rats as experimental subjects. The rats were randomly divided into a control group and a social stress group, with 30 and 33 rats in each group, respectively. The social stress group was subjected to repeated social stress using the resident-intruder paradigm, as follows:

1. Social Stress Induction: Experimental rats (intruders) were placed in the cage of an aggressive Long Evans rat (resident) for 15 minutes of physical attack followed by 15 minutes of non-physical stress (through mesh separation). This process was repeated for five consecutive days.
2. Behavioral Testing: Within 10 days of the last social stress session, all rats underwent a social interaction test. During the test, the experimental rats were allowed to freely interact with a novel same-strain rat in an open field environment for 5 minutes, and their social behaviors were recorded and analyzed via video.
3. Electrophysiological Recording: After behavioral testing, the rats were anesthetized, and single-unit extracellular recordings of MeAP neuronal spontaneous activity were performed. Additionally, MeAP-pBNST and MeAP-VMH projection neurons were identified through antidromic stimulation of the pBNST and VMH regions.

Data Processing and Analysis

The study employed various statistical methods for data analysis, including the Mann-Whitney U test, Kolmogorov-Smirnov test, and nested t-test, with logarithmic transformation applied to non-normally distributed data. Furthermore, machine learning methods were used to analyze active avoidance patterns in rat social behavior.

Key Findings

Effects of Social Stress on MeAP Neuronal Activity

The study found that social stress significantly increased the firing rate of MeAPd neurons, while MeAPv neuronal activity remained unaffected. Specific data are as follows: - The average firing rate of MeAPd neurons in the stress group was 1.44 ± 0.28 Hz, significantly higher than that of the control group (0.38 ± 0.11 Hz). - There was no significant difference in the firing rate of MeAPv neurons between the stress and control groups (stress group: 0.44 ± 0.12 Hz; control group: 0.52 ± 0.21 Hz).

Changes in MeAP-pBNST Projection Neuron Activity

The study further found that the firing rate of MeAP-pBNST projection neurons was significantly increased in the stress group (stress group: 1.33 ± 0.44 Hz; control group: 0.10 ± 0.02 Hz), while the firing rate of MeAP-VMH projection neurons showed no significant change.

Association Between Stress Intensity and Neuronal Activity

The firing rates of MeAPd and MeAP-pBNST neurons were positively correlated with the intensity of social stress (p < 0.0001). Additionally, the firing rate of MeAP-pBNST neurons was negatively correlated with the duration of social interaction in rats (p = 0.007), suggesting that the activity of these neurons may be associated with reduced social behavior.

Relationship Between Stress Susceptibility and Neuronal Activity

Based on changes in body weight, the rats were categorized into susceptible and resilient groups. The results showed that the firing rates of MeAPd and MeAP-pBNST neurons were significantly higher in the susceptible group compared to the resilient and control groups (p < 0.0001), indicating that these neurons are more sensitive to social stress in susceptible individuals.

Research Conclusions and Significance

The study demonstrates that repeated social stress may alter social behavior by increasing the activity of MeAPd and MeAP-pBNST projection neurons. This finding provides new insights into how stress affects brain social circuits and offers potential neural mechanisms for understanding social dysfunction in psychiatric disorders.

Research Highlights

1. Revealing the Critical Role of MeAPd Neurons in Social Stress: The study is the first to demonstrate the sensitivity of MeAPd neurons to social stress and their connection with pBNST projections.
2. Neural Mechanisms of Stress Susceptibility: The study found that the activity of MeAPd and MeAP-pBNST neurons was significantly increased in susceptible rats, providing a neural basis for individual differences in stress susceptibility.
3. Innovative Experimental Methods: The study combined behavioral, electrophysiological, and antidromic stimulation techniques, offering a comprehensive methodological framework for exploring the effects of stress on neural circuits.

Research Value

This study not only deepens our understanding of the neural mechanisms of social stress but also provides new targets for developing treatments for social dysfunction. Furthermore, the findings highlight the potential importance of the MeAP-pBNST circuit in stress-related psychiatric disorders.

Other Valuable Information

The study data are publicly available on GitHub (https://github.com/amielrosen/sourcedata_mea_firing.git), providing valuable resources for other researchers. Additionally, the research team plans to further explore the activity patterns of MeAP neurons in awake rats in future experiments to validate these findings in natural behavioral states.