Periodic Reporting for period 4 - CoSI (Functional connectomics of the amygdala in social interactions of different valence)
Periodo di rendicontazione: 2021-06-01 al 2023-04-30
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. However, the social brain, which is the part of the brain that controls social emotions and interactions, is still a mystery. Understanding how the brain controls social life is one of the most fascinating quests of neuroscience. At the most fundamental level, we would like to know if there are specialized circuits controlling social emotions. Furthermore, 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 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 methods allowing us to look for the neuronal circuits within the amygdala, a key structure processing emotions in the brain, which controls negative and positive emotions. We used genetic constructs that allow for the stimulation or inhibition of activity-defined neuronal subpopulations to learn about their function. Our ultimate goal was to characterize neuronal circuits in the amygdala that control negative and positive social emotions and to determine whether they are different from neural circuits that control non-social emotions, i.e. whether there is a specialized social brain.
The CoSI project has primarily focused on examining the connectivity of neuronal circuits within the amygdala and their impact on social interactions involving different emotional valence. To accomplish this, we conducted experiments using pairs of animals, where one animal was inexperienced while the other experienced emotional arousal, either positively or negatively. We focused on the central nucleus of the amygdala, which integrates signals from other parts of the brain and orchestrates behavioral and physiological emotional responses via its projections to several brainstem, hypothalamic, and cortical brain structures. Our findings revealed the presence of distinct neuronal circuits within the central amygdala that specifically mediate positive and negative socially induced emotions. These circuits exhibit unique patterns of connectivity with other regions of the brain. Additionally, we successfully identified neuronal circuits responsible for social interaction but not non-social motivation and vice versa. This discovery strongly suggests the existence of specialized circuits within the brain dedicated to the social domain, thus supporting the concept of a "social brain." Furthermore, our investigations into matrix metalloproteinase 9 (MMP-9), an enzyme involved in synaptic plasticity, and MMP-9-related neuronal circuits in the central amygdala have revealed promising therapeutic implications. By utilizing TIMP-1 designer nanoparticles to lower MMP-9 levels, we successfully reversed cognitive impairments in a mouse model of Fragile X syndrome (FXS), highlighting the potential of targeting central amygdala neuroplasticity for conditions characterized by motivation and cognitive deficits, including depression.
At the behavioral level, we found that perceiving the affective states of others helps individuals adapt their behavior, minimize risks and maximize rewards. This intriguing discovery raises questions about the prevailing assumptions regarding the evolutionary development of the ability to read emotions in others, which have long emphasized the association with maternal care. It presents compelling evidence that this capacity may have broader adaptive implications, although further research is needed to fully understand its complexities and implications. To further test this hypothesis, we sought to create experimental conditions that would allow us to track how animals utilize social cues to adapt to their environment. Traditional behavioral tests have limitations in this regard. To address this, we adapted the Eco-HAB system, originally developed in the Knapska laboratory, for studying the social behavior of mice living in a group under semi-naturalistic conditions. Using the Eco-HAB system, we found that socially acquired knowledge indeed alters the exploration patterns of familiar and novel environments. The improvements to the Eco-HAB system have led to its adoption by numerous laboratories worldwide.
At the behavioral level, we found that perceiving the affective states of others helps individuals adapt their behavior, minimize risks and maximize rewards. This intriguing discovery raises questions about the prevailing assumptions regarding the evolutionary development of the ability to read emotions in others, which have long emphasized the association with maternal care. It presents compelling evidence that this capacity may have broader adaptive implications, although further research is needed to fully understand its complexities and implications. To further test this hypothesis, we sought to create experimental conditions that would allow us to track how animals utilize social cues to adapt to their environment. Traditional behavioral tests have limitations in this regard. To address this, we adapted the Eco-HAB system, originally developed in the Knapska laboratory, for studying the social behavior of mice living in a group under semi-naturalistic conditions. Using the Eco-HAB system, we found that socially acquired knowledge indeed alters the exploration patterns of familiar and novel environments. The improvements to the Eco-HAB system have led to its adoption by numerous laboratories worldwide.
Our research has yielded significant findings regarding the ability of rodents to perceive emotional states and gather information about their environment through social cues. This challenges previous notions linking the evolutionary development of emotion reading primarily to maternal care, suggesting broader adaptive implications. Additionally, our investigations into MMP-9-related neuronal circuits in the central amygdala have uncovered exciting therapeutic potential, demonstrating that targeting these circuits with TIMP-1 designer nanoparticles can reverse cognitive impairments in a Fragile X syndrome mouse model. By utilizing the Eco-HAB system, which combines ecological validity with precise control, we can study social behaviors in mice under semi-naturalistic conditions, facilitating the understanding of evolutionarily conserved neuronal circuits and the development of valid animal models for human disorders.