Sex differences in neural activity across amygdalo-striatal network during social behaviour

Abstract

Abstract Background Social behaviour is essential for the survival of most mammalian species and is shaped by sex-dependent genetic and endocrine factors. However, how sex influences brain-wide neural dynamics during social interactions remains poorly understood. Methods Here, we investigated sex differences in neural activity across a distributed amygdalo-striatal network in freely behaving mice. Using chronically implanted electrode arrays, we simultaneously recorded extracellular activity from multiple amygdalo-striatal regions while mice performed four social discrimination tasks. Neural signals were analysed alongside video-based behavioural tracking and head acceleration measurements. Results We identified significant sex differences in neural activity that emerged even before social interaction, suggesting distinct anticipatory network states. During social interaction, sex differences were distributed across brain regions and electrophysiological features, but were most consistently expressed in the basolateral amygdala (BLA). Notably, BLA activity exhibited pronounced sex-specific, context- and time-dependent dynamics, particularly during the initial phase of social interaction. These neural differences were associated with variations in behavioural responses and movement dynamics. Conclusions Together, our findings reveal that sex shapes both baseline and interaction-driven neural activity across the social brain network, and highlight the BLA as a key node underlying sex-specific dynamics of social behaviour. Plain English summary Social behaviour is essential for survival and differs between males and females in many species, including humans and mice. These differences are influenced by biological factors such as genes and hormones, but how they are reflected in brain activity during social interactions is still not fully understood. In this study, we examined how brain activity differs between male and female mice during social behaviour. We recorded neural activity simultaneously from several brain regions involved in social and emotional processing while mice performed four different social interaction tasks. These tasks tested preferences for social versus non-social stimuli, opposite-sex animals, isolated animals, and stressed animals. At the same time, we monitored behaviour and head movements using video tracking and motion sensors. We found that males and females showed distinct patterns of brain activity even before social interaction began, suggesting that the brain may enter different “anticipatory” states depending on sex. During social interaction, sex differences in neural activity varied depending on the social context and the stage of the interaction. The strongest and most consistent differences were observed in the basolateral amygdala, a brain region known to regulate emotional and social behaviour. Interestingly, these neural differences were linked to differences in movement dynamics and social responses, particularly during the first moments of interaction. Our findings suggest that sex shapes both baseline brain activity and the way the brain responds during social encounters. This work improves our understanding of the neural basis of sex differences in social behaviour and may help inform future research on psychiatric conditions that affect social functioning differently in males and females. Highllights Simultaneous multi-site recordings revealed sex-dependent neural dynamics across an amygdalo-striatal social brain network during social behaviour. Male and female mice exhibited distinct electrophysiological signatures even before social interaction, suggesting sex-specific anticipatory neural states. High-frequency local field potential oscillations showed the strongest and most consistent sex differences across behavioural contexts and brain regions. The basolateral amygdala (BLA) emerged as a key region displaying context- and time-dependent sex differences during early social interaction. Sex-specific BLA activity correlated with movement dynamics during investigation of isolated conspecifics, linking neural network activity to behavioural responses. Graphical Abstract