Periodic Reporting for period 3 - CoSI (Functional connectomics of the amygdala in social interactions of different valence) Reporting period: 2019-12-01 to 2021-05-31 Summary of the context and overall objectives of the project People are social beings and social interactions are very important to us. We are happy when our interactions with others are successful and become preoccupied when something goes wrong with this aspect of our lives. But the social brain, that is the part of the brain that controls social emotions and interactions, is still a mystery. Understanding how brain controls social life is one of the most fascinating quests of neuroscience. At the very fundamental level, we would like to know if there are specialized circuits controlling social emotions. And even further - do positive and negative social emotions come together - or are there separate neuronal pathways controlling these two kinds of emotions? The problem is that we have no means of addressing these important questions directly in human studies. The resolution of brain functional imaging is just not good enough. Fortunately, the required resolution, at the level of single cells, is offered by the techniques used in animal models. Using simple rodent models, we have developed we are able to look for the neuronal circuits within the amygdala, a key structure processing emotions in the brain, which controls social negative and positive emotions. We use genetic constructs that allow for stimulation or inhibition of activity-defined neuronal subpopulations to learn their function. Our ultimate goal is to characterize neuronal circuits in the amygdala involved in control of negative and positive social emotions and to determine whether they are different from neural circuits controlling non-social emotions, i.e. whether there is specialized social brain. Gaining such knowledge is important to understand impairments of social interactions observed in many psychiatric disorders. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far We have focused on the central nucleus of the amygdala (CeA), which integrates signals from other parts of the brain and orchestrates behavioral and physiological emotional responses via its projections to a number of brainstem, hypothalamic and cortical brain structures. We have identified neuronal circuits within the CeA that mediate responses to social cues about imminent and remote threat. We tested the effects of stimulation and inhibition of these circuits, as well as described their connectivity with other brain structures and molecular markers that allow for identification of those neurons. We have also investigated the CeA neuronal circuits involved in positive social emotions and social motivation. We observed partial overlap between neuronal circuits mediating social and non-social approach (positive) motivation. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) We have discovered two functionally distinct neuronal networks in the central amygdala that control active and passive responses to social signals about threats. This finding is important for understanding the mechanisms of emotional contagion for several reasons. Firstly, our results support the hypothesis that emotional contagion activates similar circuitry as first-hand experience. Secondly, our data proves that social information can elicit robust and flexible behavioral responses without any prior training. Finally, we demonstrate that even naïve rodents are able to use basic socio-emotional cues to flexibly regulate their behavior instead of just mirroring the behaviour of others, which suggests that emotional contagion can be a prerequisite for higher order social skills, including empathy.We have also developed a set of behavioral and molecular tools that allow for studying neuronal circuits underlying social interactions. We will use the tools to further study the neuronal circuits in the amygdala that control social positive and negative emotions and their overlap with the circuits controlling non-social emotions.
