Researchers Reveal VTA→BLA Dopamine Neurons Selectively Control Anxiety-Related Behaviors in Singular Anxiety or Comorbid Anxiety-Depression Conditions

Date:29-03-2022   |   【Print】 【close

Anxiety disorders are the most common psychiatric illnesses, afflicting 273 million people worldwide. A substantial number of patients suffering from anxiety disorders also display depressive-like symptoms, leading to greater severity and complexity of anxiety disorders. It is unclear if a common neural mechanism controls anxiety-related behaviors in both anxiety-alone and comorbid conditions.

Recently, researchers from Shenzhen Institute of Advanced Technology (SIAT) of Chinese Academy of Sciences (CAS) and Icahn School of Medicine at Mount Sinai have established a functional role for VTA→BLA dopamine neurons controlling anxiety-related behaviors not only in anxiety-alone, but also in anxiety-depressive comorbid conditions in mice.

This study was published in the journal Nature Communications on March 22nd, 2022.

Utilizing the chronic social defeat stress (CSDS) paradigm that can induce singular or combined anxiety- and depressive-like phenotypes in mice, the researchers found that a ventral tegmental area (VTA) dopamine circuit projecting to the basolateral amygdala (BLA) selectively controlled anxiety- but not depression-like behaviors.

Utilizing circuit-dissecting ex vivo electrophysiology and in vivo fiber photometry approaches, the researchers established that expression of anxiety-like, but not depressive-like, phenotypes were negatively correlated with VTA→BLA dopamine neuron activity.

Further, bidirectional optogenetic manipulation by using inhibitory NpHR or excitatory ChR2 demonstrated a causal link between such neuronal activity and anxiety-like behaviors.

Overall, this study provides new insight into the functional role of VTA→BLA dopamine neurons in selective regulation of anxiety-related behaviors, and provides important information for developing a brain circuit map of affective disorders in the midbrain dopamine system.

Anxiety-like behavior correlates with the VTA→BLA dopamine neuron activity. (Image by SIAT)

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ZHANG Xiaomin