The altered sensitivity of acute stress induced anxiety-related behaviors by modulating insular cortex-paraventricular thalamus-bed nucleus of the stria terminalis neural circuit

作者：Di Zhao, Dan Wang, Wentao Wang, Juanjuan Dai, Minghu Cui, Min Wu, Cuilan Liu, Jing Liu, Fantao Meng, Kaixin Wang, Fengai Hu, Dunjiang Liu, Changyun Qiu, Wei Li, Chen Li · 发表于：Neurobiology of Disease · 年份：2022 · DOI：10.1016/j.nbd.2022.105890 · 被引用次数：45 · 研究领域：Neural dynamics and brain function、Memory and Neural Mechanisms、Functional Brain Connectivity Studies

The dysregulation of neuronal networks contributes to the etiology of psychiatric diseases, including anxiety. However, the neural circuits underlying anxiety symptoms remain unidentified. We observed acute restraint stress activating excitatory neurons in the paraventricular thalamus (PVT). Activation of PVT neurons caused anxious behaviors, whereas suppression of PVT neuronal activity induced an anxiolytic effect, achieved by using a chemogenetic method. Moreover, we found that the PVT neurons showed plentiful neuronal projections to the bed nucleus of the stria terminalis (BNST). Activation of PVT-BNST neural projections increased the susceptibility of stress-induced anxiety-related behaviors, and inhibition of this neural circuit produced anxiolysis. The insular cortex (IC) is an important upstream region projecting to PVT. Activation of IC-PVT neuronal projections enhanced susceptibility to stress induced anxious behaviors. Inhibiting this neural circuit suppressed anxious behaviors. Moreover, anterograde monosynaptic tracing results showed that the IC exerts strong neuronal projections to PVT, forming synaptic connections with its neurons, and these neurons throw extensive neuronal fibers to form synapse with BNST neurons. Finally, our results showed that ablation of neurons in PVT receiving monosynaptic input from IC attenuated the anxiety-related phenotypes induced by activating IC neurons. Lesions of the neurons in BNST synaptic origination from PVT blocked the anxie...