Amygdala is widely known as a critical neural hub for modulating negative emotions such as fear and anxiety. Recent studies have shown that the basolateral amygdala (BLA) has reciprocal innervation, which plays an important role in regulating social interaction and associative memory. However, the connectivity pattern and functional role of the contralateral projecting BLA neurons in stress-related anxiety are not fully understood. Here, using the virus tracing strategy, we first characterized the connectivity pattern of the contralateral projecting neurons in BLA. Then, we examined the effect of stress on the functional changes of those specific neuronal populations using a mouse model of inescapable footshock stress. The results showed that the fibers of the contralateral projecting BLA neurons labeled by enhanced green fluorescent protein (EGFP) have no collateral projections to the ipsilateral or contralateral hippocampus. Interestingly, they have some collateral projections to the ipsilateral medial prefrontal cortex. Behavioral results showed that footshock stress increases the anxiety-like behavior in mice; however, the excitatory synaptic transmission and intrinsic excitability of the contralateral projecting BLA neurons measured by whole-cell patch clamp recording did not change after stress exposure. In conclusion, our results indicate that contralateral projecting BLA neurons may not contribute to footshock stress-related anxiety-like behavior.

Single prolonged stress (SPS) is a well-established and most frequently used rat model to induce post-traumatic stress disorder (PTSD)-like symptoms, which helps to understand the neurobiological mechanisms as well as developing novel therapeutic strategies for PTSD. However, whether such stress model works efficiently in mice remains unknown. In the present study, we established a mouse SPS (mSPS) model by exposing C57BL/6J mice to a series of multimodal stressors on a single day, then the anxiety-like behavior was measured by open-field test, elevated plus maze test, dark-light box, and novelty-suppressed feeding test. Our results showed that mSPS had no significant effect on the anxiety-like behavior in mice after different days of recovery. The expression of the glucocorticoid receptor and brain-derived neurotrophic factor (BDNF), two proteins that highly associated with stress-related behaviors, also remained unaltered in both the amygdala and hippocampus. By contrast, the protein levels of NR2A and NR2B, two main subunits of the N-methyl-D-aspartate receptor (NMDAR), was reduced in the hippocampus, but not amygdala. In conclusion, our results indicate that mSPS may not be an efficient mouse model to explore the pathophysiology of PTSD-related anxiety-like behavior.