Dissociable contributions of the amygdala and ventral hippocampus to stress-induced changes in defensive behavior

Stress can have profound consequences on mental health. While much is known about the neural circuits supporting associative memories of stressful events, our understanding of the circuits underlying the non-associative impacts of stress, such as heightened stress sensitivity and anxiety-related behavior, is limited. Here, we demonstrate that the ventral hippocampus (vHC) and basolateral amygdala (BLA) support distinct non-associative behavioral changes following stress. Inhibiting stress-induced protein synthesis in the BLA blocked subsequent increases in stress sensitivity but not anxiety-related behaviors. Conversely, inhibiting stress-induced protein synthesis in the vHC blocked subsequent increases in anxiety-related behavior but not stress sensitivity. Inhibiting neuronal activity in the BLA and vHC during the assessment of stress sensitivity or anxiety-related behavior recapitulated these structures’ dissociable contributions to defensive behavior. Lastly, blocking the associative memory of a stressor had no impact on stress-induced changes in anxiety-related behavior. These findings highlight that multiple memory systems support the long-lasting effects of stress.