Brain cells overactive after social trauma impair social reward and promote social avoidance

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The prior social trauma is encoded by a group of stress/threat-responsive brain cells that become hyperactive during subsequent interaction with non-threatening social targets. As a result, social goals that were previously rewarded are now seen as social threats, reinforcing generalized society avoidance and processing of social rewards that can contribute to mental disorders, according to a study conducted by researchers at the Mount Sinai Brain and Body Research Center and published in 30. november in nature.

In humans, studies have shown that social trauma impairs the brain’s reward function to the point that social interaction is no longer rewarding, leading to extreme social avoidance. In rodents, the stress of chronic social defeat, a paradigm of social trauma, has been used to understand the brain circuit mechanisms underlying susceptibility to stress versus resilience, yet little is known about its effect on social reward. Previous studies evaluated social interaction with adult mice similar to those used as aggressors to induce social trauma. Social avoidance under these conditions likely reflects fear or submissive behaviour, rather than altered social reward.

To better understand how painful social experience affects social reward, we tested social interaction and social preference with a young rat of the same sex that is rewarding under control conditions. We found that, following the stress of chronic social defeat, a subset of male and female mice were described as being prone to avoiding social interactions with juvenile mice and not developing context-dependent social reward after encounters with them.”


Long Li, PhD, instructor of neurology at the Icahn School of Medicine at Mount Sinai and lead author of the study

In the study, adult male and female rats were subjected to chronic social defeat stress, in which they were repeatedly put down by aggressive rats, followed by a social interaction test, in which an experimental rat was placed in a cage with a larger aggressive rat behind a barrier and the amount of time it took to interact was measured. . The mice were classified as resilient or under stress based on their social interaction behaviour. This was followed by an additional social interaction test called the resident intruder test, in which a 4-6-week-old same-sex rat (juvenile) was introduced into the subject’s home and allowed to interact freely. This was then followed by a socially conditioned place preference test in which control rats were conditioned to juvenile rats to assess their preference for the reward of social targets. During the resident intruder test, control and flexed rats showed similar social behaviors toward the event, including the amount of active interaction (approach, close follow, and sniff). Rats in these groups rarely withdraw from social contact with juveniles and freely approach and investigate them. Conversely, rats exposed to stress showed less active social investigation, a longer delay before the first social bout (“latency”), and significantly greater social avoidance. Furthermore, social investigation time, social avoidance, and investigation latency are related to social interaction ratios during testing with an aggressive adult mouse. These results show that susceptible mice not only exhibit avoidance towards aggressive male mice, but also to non-threatening juvenile mice of the same sex.

To identify potential brain regions involved in heightened social threat, advanced histological and imaging techniques were used to identify a population of stress-responsive/lateral barrier (NTLS) neurons activated by social interactions to events only in susceptible rats, but not in resilient control or Uncompressed.

Finally, the team used optogenetic and chemogenetic strategies to either activate or inhibit NTLS neurons and their terminal connections.

said Scott Russo, PhD, professor of neuroscience and director of the Center for Active Neuroscience and the Brainbody Research Center. “So we ultimately think that when mice experience social trauma, their ability to experience social reward is blocked by these NTLS cells.”

These findings provide an important basis for understanding the neural mechanisms underlying post-traumatic social reward processing. The Mount Sinai team plans human studies to test the importance of lateral barrier circuits in mediating social threat perception and reward desensitization in trauma victims.

source:

Journal reference:

night , et al. (2022) Social trauma triggers the lateral barrier circuit to close social reward. nature. doi.org/10.1038/s41586-022-05484-5.

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