Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors

Anxiety disorders are complex diseases, and often co-occur with depression. It is as yet unclear if a common neural circuit controls anxiety-related behaviors in both anxiety-alone and comorbid conditions. Here, utilizing the chronic social defeat stress (CSDS) paradigm that induces singular or combined anxiety- and depressive-like phenotypes in mice, we show that a ventral tegmental area (VTA) dopamine circuit projecting to the basolateral amygdala (BLA) selectively controls anxiety- but not depression-like behaviors. Using circuit-dissecting ex vivo electrophysiology and in vivo fiber photometry approaches, we establish that expression of anxiety-like, but not depressive-like, phenotypes are negatively correlated with VTA -> BLA dopamine neuron activity. Further, our optogenetic studies demonstrate a causal link between such neuronal activity and anxiety-like behaviors. Overall, these data establish a functional role for VTA -> BLA dopamine neurons in bi-directionally controlling anxiety-related behaviors not only in anxiety-alone, but also in anxiety-depressive comorbid conditions in mice. Anxiety and depression are highly comorbid, yet the distinct or shared neurobiological correlates of anxiety remain elusive. Here, Morel et al. define that the midbrain projection to the basolateral amygdala control anxiety but not depression.

Automated summary

This study demonstrates that ventral tegmental area (VTA) dopamine neurons projecting to the basolateral amygdala (BLA) selectively control anxiety-like behaviors, but not depression-like behaviors. These findings provide important insights into the neural correlates of anxiety and depression.