The contribution of metaplasticity to stress-related psychopathologies within the amygdala

The amygdala contributes to the formation of emotional memory by modulating other brain regions, such as the hippocampus and medial prefrontal cortex. Under extreme conditions, abnormal plasticity is induced in these regions by the amygdala. As a result, trauma-induced psychopathologies such as depression or posttraumatic stress syndrome develop. Emotional experiences, in turn, induce long-term plasticity in the amygdala itself. Such changes within the amygdala, which then have secondary effects on other brain regions such as the hippocampus and medial prefrontal cortex, represent a form of metaplasticity. In the past, we have investigated the impact of amygdala plasticity on emotional behavior and resilience. Specifically, gene expression was locally and specifically regulated with lentiviral vectors such that experience-dependent metaplasticity was replicated in the amygdala.

This approach proved to be highly effective and allowed to relate persistent changes in amygdala functions to stress-induced psychopathologies and resilience. The approach is invoked here to link synaptic plasticity and metaplastic effects in the amygdala to stress response and trauma. In a continuation of this approach, this project will modulate the BDNF-TrkB signaling pathway in amygdala principal neurons by lentiviral intervention to examine subsequent metaplastic changes in the hippocampus and prefrontal cortex that are essential for processing stress and trauma. Subsequently, animals are exposed to various fear- and trauma-inducing conditions. Specifically, we examine (1) anxiety behavior and standard conditions in the absence of an acute threat (2) anxiety behavior after acute exposure to stress (3) the ability to learn under stress, which provides information about stress resistance (4) the propensity to develop psychopathological symptoms after a traumatic event The behavioral tests are then linked to electrophysiological and morphological analyses. This multiparametric analysis allows relating aspects of anxiety behavior (fear, pathological anxiety, stress resistance) to changes in plasticity and metaplasticity in the amygdala. Previous studies showed a substantial influence of individual differences to respond to stress. Here, we apply our recently developed method to classify "responders" and "non-responders". Individual classification allows higher discriminatory power to relate electrophysiological and morphological changes to behavioral changes.