Prior negative experience biases activity of medial amygdala during inter-strain social engagement in male rats.

Abstract

Social recognition is an essential part of social function and often promotes specific social behaviors based on prior experience. Social and defensive behaviors in particular often emerge with prior experiences of familiarity or novelty/stress, respectively. This is also commonly seen in rodents towards same-strain and inter-strain conspecifics. Medial amygdala (MeA) activity guides social choice based on age and sex recognition and is sensitive to social experiences. However, little is known about whether the MeA exhibits differential responses based on strain or how this is impacted by experience. Social stress impacts posterior MeA (MeAp) function and can shift measures of social engagement. However, it is unclear how stress impacts MeAp activity and contributes to altered social behavior. The primary goal of this study in adult male Sprague Dawley rats was to determine whether prior stress experience with a different strain (Long Evans) rat impacts MeAp responses to same-strain and different-strain conspecifics in parallel with a change in behavior using in vivo fiber photometry. We found that MeAp activity was uniformly activated during social contact with a novel same-strain rat during a three-chamber social preference test following control handling but became biased towards a novel different-strain rat following social stress. Socially stressed rats also showed initially heightened social interaction with novel same-strain rats but showed social avoidance and fragmented social behavior with novel different-strain rats relative to controls. These results indicate that heightened MeAp activity may guide social responses to novel, threatening rather than non-threatening social stimuli after stress.Significance Statement We are challenged daily to interpret social information and decide on appropriate behaviors based on that information. Social decisions often favor conspecifics, especially those that are most similar, and this is further enhanced after stressful experiences. While this preference is conserved across mammalian species, its neural substrates are not known. We found that activity of the rodent posterior medial amygdala (MeAp), a brain region critical for early processing of social cues, distinguishes same- and different-strain conspecifics, and responds differently to same-strain cues in the presence of a threatening different-strain conspecific. These results provide novel insight into how social threats redirect the encoding of social stimuli and can help explain how individuals balance different types of social information to direct behavior.