Stress-Induced Differential Regulation Leads to Decoupling of the Activity between mPFC and Amygdala

Abstract

Exposure to severe stress leads to the development of psychiatric disorders. Clinical studies have shown that three brain areas involved in learning and memory—the hippocampus, amygdala and medial prefrontal cortex (mPFC)—undergo distinct changes with stress disorders. While the hippocampus and mPFC show impairment in structural and functional changes, the amygdala shows an enhancement. Despite these three brain regions having strong anatomical connections, most of these studies focus on individual brain regions. However, recent studies have shown that these connections between regions have strong functional implications. The connectivity between the mPFC and the amygdala has recently been shown to be crucial for fear expression (Likhtik et al., 2014). The effect of stress on the functional connections between these regions is poorly understood. Therefore, we performed in-vivo local field potential recordings from the mPFC and the amygdala in awake behaving rats during fear expression. We found that stress differentially regulates the activity in the mPFC and the amygdala during fear expression. Consistent with cellular findings, the activity in the amygdala is upregulated by stress during fear expression. However, the activity of the mPFC is unaffected by stress during fear expression. We also found that stress causes a decoupling between the activity in the amygdala and mPFC. Interestingly, an earlier study showed that stress strengthens the coupling between the hippocampus and the amygdala (Ghosh et al., 2013). Therefore, although chronic stress impairs structure and function in both the hippocampus and mPFC, the interactions of these two areas and the amygdala appear to be affected in a contrasting fashion. Functional connectivity gets stronger from amygdala to hippocampus but it gets disrupted between mPFC and amygdala. Future studies need to focus on mechanisms involved in these connectivity changes.