Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Friedman Brain Institute, Center for Affective Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Commun. 2022 Mar 22;13(1):1532. doi: 10.1038/s41467-022-29155-1.
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.
焦虑症是一种复杂的疾病，常与抑郁症共病。目前尚不清楚是否存在一个共同的神经回路来控制单纯焦虑症和共病情况下的焦虑相关行为。在这里，我们利用慢性社会挫败应激（CSDS）范式，在小鼠中诱导单一或合并的焦虑和抑郁样表型，结果表明腹侧被盖区（VTA）多巴胺投射到基底外侧杏仁核（BLA）的回路选择性地控制焦虑样行为，而不是抑郁样行为。通过分离回路的离体电生理学和在体光纤光度测定方法，我们确定焦虑样表型而非抑郁样表型的表达与 VTA→BLA 多巴胺神经元活动呈负相关。此外，我们的光遗传学研究表明，这种神经元活动与焦虑样行为之间存在因果关系。总的来说，这些数据确立了 VTA→BLA 多巴胺神经元在双向控制焦虑相关行为中的功能作用，不仅在单纯焦虑症中，而且在焦虑抑郁共病的小鼠模型中也存在这种作用。
