Potentiated GABAergic neuronal activities in the basolateral amygdala alleviate stress-induced depressive behaviors

Abstract

Aims

Major depressive disorder is a severe psychiatric disorder that afflicts ~17% of the world population. Neuroimaging investigations of depressed patients have consistently reported the dysfunction of the basolateral amygdala in the pathophysiology of depression. However, how the BLA and related circuits are implicated in the pathogenesis of depression is poorly understood.

Methods

Here, we combined fiber photometry, immediate early gene expression (c-fos), optogenetics, chemogenetics, behavioral analysis, and viral tracing techniques to provide multiple lines of evidence of how the BLA neurons mediate depressive-like behavior.

Results

We demonstrated that the aversive stimuli elevated the neuronal activity of the excitatory BLA neurons (BLA^CAMKII neurons). Optogenetic activation of CAMKII neurons facilitates the induction of depressive-like behavior while inhibition of these neurons alleviates the depressive-like behavior. Next, we found that the chemogenetic inhibition of GABAergic neurons in the BLA (BLA^GABA) increased the firing frequency of CAMKII neurons and mediates the depressive-like phenotypes. Finally, through fiber photometry recording and chemogenetic manipulation, we proved that the activation of BLA^GABA neurons inhibits BLA^CAMKII neuronal activity and alleviates depressive-like behavior in the mice.

Conclusion

Thus, through evaluating BLA^GABA and BLA^CAMKII neurons by distinct interaction, the BLA regulates depressive-like behavior.