Neuronal correlates of social behavior in health and disease
The current impasse in developing mechanism-based therapies for neuropsychiatric disorders can be overcome by adopting a symptom and circuit-specific approach. The complexity of neuronal circuits involved in controlling behaviors necessitates a focused approach targeting specific brain regions that serve as hubs of high connectivity. One such hub is the central amygdala (CeA), which plays a crucial role in motivation.
We identified specific neuronal circuits within the CeA that are critical for initiating and maintaining social interaction, as well as recognizing negative emotional states in others. We also identified the circuits involved in modulation of food motivation. Interestingly, the social- and food-related circuits only partially overlap. Importantly, our studies have demonstrated the involvement of the human CeA in processing social and food-related stimuli.
These findings provide a promising avenue for developing therapeutic interventions that target specific circuits within the CeA. By focusing on the unique roles of these circuits in various behaviors and emotional processes, researchers can potentially develop circuit-focused treatments for motivation disorders such as depression or autism spectrum disorder.
Dr. Ewelina Knapska has been a group leader at the Nencki Institute in Warsaw since 2012. In 2013 she was promoted to Professor of the Institute, and since 2018 she has been vice-President of the Centre of Excellence for Neural Plasticity and Brain Disorders (BRAINCITY). Her research aims to understand the neural circuit mechanisms controlling social interaction and emotion-related learning. She was one of the first to describe sharing others’ emotions and their brain correlates in rodents (Knapska et al., Proc Natl Acad Sci U S A. 2006).
This discovery has started a new line of research on the brain mechanisms underlying socially transferred emotions and social learning. In 2016 she was awarded a Starting Grant from the European Research Council (ERC) to study functional connectivity of the amygdala in social behavior. With the behavioral protocols and c-fos-dependent tracing of functional connectivity of activated neurons (Knapska et al., Proc Natl Acad Sci U S A. 2012) she developed, she has shown that reading the emotions of others can provide information about the proximity of danger and that distinct central amygdala circuits are recruited by socially signaled imminent and remote danger (Andraka, Kondrakiewicz et al. Current Biology, 2021).
She has also studied the role of the central amygdala circuits in learning, discovering that matrix metalloproteinase 9 (MMP-9)-related circuits are indispensable for reward learning (Knapska et al., J. Neurosci. 2013; Puscian et al., Br J Pharmacol., 2021), in particular for approach motivation (Lebitko et al., BiorXiv preprint), which suggests the target of selective treatment. Accordingly, she has recently shown that normalizing MMP-9 activity in the central amygdala rescues impaired reward learning in the Fragile X syndrome model (Puscian et al., Mol. Psychiatry).