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Activation of ventrolateral orbital cortex improves mouse neu
Recombinant AAV1-Cre was used to further verify the antianxiodepressive effect of Sm-VLO projection. (From BrainVTA)
The viruses used in this article from BrainVTA are in the table below
CRE Recombinase  PT-0136 rAAV-hSyn-Cre-WPRE-pA
Hai-Yan Sheng, Su-Su Lv, Ya-Qi Cai, Wu Shi, Wei Lin, Ting-Ting Liu, Ning Lv, Hong Cao, Ling Zhang, Yu-Qiu Zhang
Pub Date: 2020-10-02, DOI: 10.1172/jci.insight.133625, Email:
Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve–induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus–VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism–based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.

Figure 1. Activation of VLO neurons induced an antianxiodepressive effect in TN mice.
The study is aimed to explore the underlying mechanisms of depression and anxiety in patients suffering from neuropathic pain. Using a chronic constriction injury of infraorbital nerve (CION) mouse model and chemogenetic, optogenetic manipulation and a series of behavioral tests, this study provides preclinical evidence that addresses the anxiodepressive consequences of neuropathic pain.
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