Heightened fear responding and social dysfunction are commonly seen in individuals suffering from debilitating fear-related disorders, such as Post-Traumatic Stress Disorder (PTSD). Exposure-based treatments are often ineffective at minimizing robust fear responses. Adolescents are especially prone to the development of fear- and stress-related disorders as well as symptom persistence following therapeutic interventions. Understanding developmental differences in the persistence of fear could therefore lead to more targeted, age-appropriate interventions. Directly experienced traumatic events are significant triggers in anxiety disorders and PTSD. However, adolescent observation of trauma or abuse also increases risk of diagnosis. The impact of observed trauma depends on the social sensitivity of the observer, which is high during adolescence. This social sensitivity combined with ongoing brain maturation may produce adolescent vulnerabilities for these disorders. The investigation of factors that contribute to behavioral and biological changes across the lifespan is critical for a thorough understanding of adaptive fear responding. The goal of this proposal is to identify the factors that contribute to socially learned fear in adults and adolescents, and how these factors lead to persistent fear behavior during adolescence. We will use social fear learning (SFL), which requires social interaction and social inference, and requires amygdala circuits to learn and retain fear. We hypothesize that changes in social sensitivity and amygdala circuitry from adolescence to adulthood contribute to differences in how SFL is learned and retained. We will test this general hypothesis in two specific aims.
Aim 1 will determine how changes in social drive between adults and adolescents impact SFL and retention as well as cortico-amygdala synaptic strength using whole cell electrophysiology.
Aim 2 will target how socially-inferred fear responding may change with acute manipulations in observed fear using optogenetics, and the impact this has on synaptic strength in the amygdala using whole cell electrophysiology. These results will provide information for new therapeutic strategies to understand the developmental differences in how fear is retained through changes in social drive.
It is estimated that 31.1% of the population will experience an anxiety disorder, with adolescents at a disadvantage due to high chances of symptom persistence following treatment. Ongoing brain maturation and higher social sensitivity provide a potential source of adolescent vulnerability, as well as an unexplored opportunity. Understanding age-related changes in social function and fear processes may uncover a new avenue for development of more effective, targeted therapies.
