Early-life stress induces anxiety-like behaviors and activity imbalances in the medial prefrontal cortex and amygdala in adult rats

Early-life stress increases the prevalence of psychiatric diseases associated with emotional dysregulation. Emotional regulation requires the inhibitory influence of the medial prefrontal cortex (mPFC) on amygdalar activity, and dysfunction of this system is believed to induce anxiety. Because mPFC and amygdala have dense reciprocal connections and projections between them continue to develop until adolescence, early-life stress may impair the function of this circuit and cause emotional dysregulation. We examined the effects of stress during circuit development on anxiety-like behaviors, neural activities in the mPFC and amygdala, and impulse transmission in the mPFC-amygdala circuit in adult rats. Early-life stress, unpredictable stress twice a day for 12days following early weaning, increased anxiety-like behaviors in the open-field and elevated plus-maze tests. In the open-field test, stress altered Fos expression in the mPFC and amygdala. Compared to non-stressed rats, which were exposed to neither unpredictable stress nor early weaning, stressed rats exhibited decreased Fos expression in the right superficial layers of the infralimbic cortex and increased Fos expression in the right basolateral amygdala and both sides of the central amygdala. Electrophysiological analysis revealed that excitatory latencies of mPFC neurons to amygdalar stimulation in stressed rats were significantly longer than control rats in the right, but not left, hemisphere. Stress had no effect on excitatory latencies of amygdalar neurons to mPFC stimulation in the mPFC-amygdala circuits in the both hemisphere. These data suggest that early-life stress impairs the mPFC-amygdala circuit development, resulting in imbalanced mPFC and amygdala activities and anxiety-like behaviors.