Chronic optogenetic manipulation of basolateral amygdala astrocytes rescues stress-induced anxiety.

Chronic exposure to stressors can disrupt normal brain function and induce anxiety-like behavior and neurobiological alterations in the basolateral amygdala (BLA). Here, we showed that unpredictable chronic mild stress (UCMS) induced anxiety-like behavior, lowered glutamatergic neuronal activity and reactive astrocytes in the BLA. Using optogenetic tools, we found that activation of BLA glutamatergic neurons did not rescue anxiety-like behavior in stressed mice. In contrast, however, optogenetic activation of the BLA astrocytes relieved stress-induced anxiety, and, interestingly, chronic optogenetic manipulation fully restored the UCMS-induced behavioral and neurobiological dysfunctions, including anxiety-like behavior, lower c-Fos expression in the BLA, S100 overexpression in the BLA, and higher serum corticosterone concentration. Thus, our findings suggest that chronic manipulation of BLA astrocytes is a potential therapeutic intervention target for pathological anxiety.