The Role Of Neuronal Activity Of Basolateral Amygdala In Regulating Stress-Related Affective Behavior In Mice

Chronic stress leads to multiple psychiatric disorders,including social and anxiety disorders,which are associated with the hyperactivation of basolateral amygdala(BLA).Stressful life events are unavoidable throughout the lifespan;however,the occurrence and development of psychiatric disorders vary across individuals even when they are exposed to stress with the same intensity and duration.While most of them show resilience to stress(stress resilience),that is,they take positive coping strategies to make appropriate stress response;some individuals shows obvious stress vulnerability(stress susceptibility),that is,they take negative coping strategies,resulting in psychological and physiological dysfunction,and ultimately affect physical and mental health.Amygdala is one of the core brain areas mediating brain’s coping with stress.A large number of studies have shown that stress-induced affective disorders are closely related to the structural and functional remodelings of basolateral amygdala(BLA)neurons.Aberrant activation of BLA neurons was observed in both animal models and patients with anxiety disorder.However,it is not clear whether there are differences in the dynamic changes of BLA neuron activity between stress resilient and susceptible individuals,as well as the role of these differences in stress-induced affective disorder.In this study,we employed a mice model of chronic social defeat stress(CSDS)and social interaction test(SI)to divide the mice into susceptible(SI-sus)and resilient(SI-res)subgroups.The former shows robust social avoidance after CSDS,while the latter still shows normal social interaction.The changes of BLA neuronal dynamic activity in the two subgroups were detected by fiber photometry and patch-clamp recording.Finally,the anxiety-like behavior of each group of mice was tested by open field test(OFT)and elevated plus maze(EPM),then the correlation between anxietylike behavior and neuronal excitability was analyzed.The fiber photometry results showed that acute defeat stress rapidly increased neuronal activity in BLA.However,CSDS significantly increased the calcium activity of BLA neurons in both SI-sus and SI-res mice.Patch-clamp recording results also showed that the intrinsic excitability of BLA neurons in SI-sus and SI-res mice was significantly increased.Further studies showed that the anxiety-like behavior of both groups was significantly increased,although social disorder was only observed in SIsus mice after CSDS.Subsequently,we found that the increased activity of BLA neurons and the increased anxiety behavior of mice induced by CSDS still existed 20 days after CSDS.Finally,correlation analysis found that the increase of intrinsic excitability of BLA neurons induced by CSDS was significantly and negatively correlated with the time spent in the center of the open field and time spent in the open arm of the elevated plus-maze,but not correlated with the SI ratio.In conclusion,our results indicate that the activity of BLA neurons in both SI-sus and SI-res mice divided by social interaction test was significantly enhanced after CSDS,and this effect is persistent.However,the enhancement of BLA neuron activity was not correlated with stress-induced social disorder behavior but significantly correlated with anxiety behavior.These findings provide new insight into our understanding of the role of amygdala neuronal activity in mediating stress-related psychiatric disorders.