Sex differences in the delayed impact of acute stress on the amygdala.

There is accumulating evidence that stress triggers specific temporal patterns of morphological plasticity in the amygdala, a brain area that plays a pivotal role in the debilitating emotional symptoms of stress-related psychiatric disorders. Acute immobilization stress is known to cause a delayed increase in the density of dendritic spines on principal neurons in the basolateral amygdala (BLA) of rats. These neuronal changes are also accompanied by a delayed enhancement in anxiety-like behavior. However, these earlier studies used male rats, and the delayed behavioral and synaptic effects of acute stress on the BLA of female rats remain unexplored. Here, using whole-cell recordings in rat brain slices, we find that a single exposure to 2-h immobilization stress leads to an increase, 10 days later, in the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded from lateral amygdala (LA) principal neurons in male rats. Further, acute stress also causes a reduction in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in LA neurons 10 days after acute stress. In striking contrast, excitatory and inhibitory synaptic transmission in the LA of female rats does not exhibit any delayed change despite exposure to the same acute stress. Finally, we examined the functional impact of these contrasting synaptic changes at the behavioral level. Male rats exhibit a delayed increase in anxiety-like behavior on the elevated plus-maze 10 days after acute stress. However, the same stress does not lead to a delayed anxiogenic effect in female rats. Together, these results demonstrate that the delayed modulation of the balance of synaptic excitation and inhibition in the amygdala, as well as anxiety-like behavior, differ between males and females. These findings provide a framework, across biological scales, for analyzing how affective symptoms of stress disorders vary between the sexes.