Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors
Carole Morel, Sarah Montgomery, Long Li, Romain Durand-de Cuttoli, Emily M. Teichman, Barbara Juarez, Nikos Tzavaras, Stacy M. Ku, Meghan E. Flanigan, Min Cai, Jessica J. Walsh, Scott J. Russo, Eric J. Nestler, Erin S. Calipari, Allyson K. Friedman, Ming‐Hu Han
Abstract
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.