Early life stress impairs VTA coordination of BLA network and behavioral states.

Abstract

Motivated behaviors, such as social interactions, are governed by the interplay between mesocorticolimbic structures, such as the ventral tegmental area (VTA), basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adverse childhood experiences and early life stress (ELS) can impact these networks and behaviors, which is associated with increased risk for psychiatric illnesses. While it is known that the VTA projects to both the BLA and mPFC, the influence of these inputs on local network activity which govern behavioral states - and whether ELS impacts VTA-mediated network communication - remains unknown. Our study demonstrates that VTA inputs influence BLA oscillations and entrainment of mPFC activity in mice, and that ELS weakens the ability of the VTA to coordinate BLA network states, while also impairing dopaminergic signaling between VTA and BLA. Optogenetic stimulation of VTA_BLA terminals decreased social interaction in ELS mice, which can be recapitulated in control mice by inhibiting VTA-BLA communication. These data suggest that ELS impacts social reward via the VTA-BLA dopamine network.Significance Statement It is well established that oscillatory states in the basolateral amygdala (BLA) govern behavioral states. However, a gap in our knowledge exists regarding the mechanisms mediating transitions between BLA network states. Here we demonstrate a novel mechanism modulating BLA network states involving dopamine inputs from the VTA. Further, we demonstrate that early life stress, a major risk factor for psychiatric illnesses, impairs the ability of dopaminergic inputs from the VTA to coordinate BLA and mPFC network states. Thus, this study provides a novel mechanism mediating transitions between oscillatory states in the BLA which are well documented to govern behavioral states and demonstrates pathological perturbations in the ability of the VTA to coordinate BLA network states following early life stress.