Activation of ventrolateral orbital cortex improves mouse neuropathic pain–induced anxiodepression
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
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
View: Text | PDF
Research Article Neuroscience

Activation of ventrolateral orbital cortex improves mouse neuropathic pain–induced anxiodepression

Abstract

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.

Authors

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

×

Figure 4

The excitability of VLO excitatory pyramidal neurons decreased in TN mice.

Options: View larger image (or click on image) Download as PowerPoint
The excitability of VLO excitatory pyramidal neurons decreased in TN mic...
(A) Number of spikes induced by injected currents in VLO CaMK2A+ pyramidal neurons from sham and CION mice. ***P < 0.001, 2-way ANOVA followed by post hoc Student-Newman-Keuls test; n = 20 (sham) and 19 (CION; cells). (B) Examples of AP responses to positive current steps recording from CaMK2A+ pyramidal neurons in the VLO from sham and CION mice. (C and D) Quantification of AP thresholds (C) and half-width (D) in VLO CaMK2A+ pyramidal neurons from sham and CION mice. **P < 0.01, ***P < 0.001, 2-sided Student’s t test; n = 20 (sham) and 19 (CION; cells). (E) Number of spikes induced by injected currents in rACC CaMK2A+ pyramidal neurons from sham and CION mice. ***P < 0.001, 2-way ANOVA followed by post hoc Student-Newman-Keuls test; n = 19 (both sham and CION; cells). (F) Examples of AP responses to positive current steps recording from CaMK2A+ pyramidal neurons in the rACC from sham and CION mice. (G) Quantification of AP thresholds in rACC CaMK2A+ pyramidal neurons from sham and CION mice. **P < 0.01, 2-sided Student’s t test; n = 19 (both sham and CION; cells). (H) Examples of multiple channel recordings in vivo during TST in 1 sham and 1 CION mice. (I) Photomicrograph of coronal section showing the site of multiple-channel electrode implantation in unilateral VLO (contralateral to the CION). Scale bar: 500 μm. (J) Example showing that VLO pyramidal neurons has a long duration compared with interneurons in multiple channel electrophysiological recordings in vivo. (K) The spontaneous firing rate of VLO pyramidal neurons in TN mice was lower during the TST. *P < 0.05, 2-sided Student’s t test; n = 26 (sham) and 28 (CION; cells).