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A neural circuit for comorbid depressive symptoms in chronic
RV-DsRed virus was used for retrograde monosynaptic tracing,hChR2 and eNpHR3.0 viruses were used for optogenetic manipulation. hM3D(Gq) and hM4D(Gi) viruses were used for chemogenetic manipulations, Cre-dependent AAV was used for the anterograd tracing of the CeA-LHb circuit. (all viruses were packaged by BrainVTA)
The viruses used in this article from BrainVTA are in the table below
Tracing Helper  PT-0023 rAAV-Ef1α-DIO-RVG-WPRE-pA
 PT-0062 rAAV-Ef1α-DIO-EGFP-2a-TVA-WPRE-pA
RV  R01002 RV-ENVA-ΔG-DsRed
Optogenetic  PT-0002 rAAV-Ef1α-DIO-hChR2 (H134R)-mCherry-WPRE-pA
 PT-1317 rAAV-hSyn-hChR2-EYFP-WPRE-pA
 PT-0150 rAAV-hSyn-hChR2-mCherry-WPRE-pA
 PT-0003 rAAV-Ef1α-DIO-eNpHR3.0-EYFP-WPRE-pA
Chemogenetic  PT-0042 rAAV-Ef1α-DIO-hM3D(Gq)-mCherry-WPRE-pA
 PT-0043 rAAV-Ef1α-DIO-hM4D(Gi)-mCherry-WPRE-pA
Control  PT-0013 rAAV-Ef1α-DIO-mCherry-WPRE-pA
Pub Date: 2019-08-26,  DOI: 10.1038/s41593-019-0468-2,  Email:
Wenjie Zhou, Yan Jin, Qian Meng, Xia Zhu, Tongjian Bai, Yanghua Tian, Yu Mao, Likui Wang, Wen Xie, Hui Zhong, Na Zhang, Min-Hua Luo , Wenjuan Tao, Haitao Wang, Jie Li, Juan Li, Ben-Sheng Qiu, Jiang-Ning Zhou, Xiangyao Li , Han Xu, Kai Wang, Xiaochu Zhang, Yong Liu, Gal Richter Levin , Lin Xu  and Zhi Zhang   
Comorbid depressive symptoms (CDS) in chronic pain are a common health problem, but the neural circuit mechanisms underlying these symptoms remain unclear. Here we identify a novel pathway involving 5-hydroxytryptamine (5-HT) projections from the dorsal raphe nucleus (5-HTDRN) to somatostatin (SOM)-expressing and non-SOM interneurons in the central nucleus of the amygdala (CeA). The SOMCeA neurons project directly to the lateral habenula, an area known involved in depression. Inhibition of the 5-HTDRN→SOMCeA pathway produced depression-like behavior in a male mouse model of chronic pain. Activation of this pathway using pharmacological or optogenetic approaches reduced depression-like behavior in these mice. Human functional magnetic resonance imaging data showed that compared to healthy controls, functional connectivity between the CeA-containing centromedial amygdala and the DRN was reduced in patients with CDS but not in patients in chronic pain without depression. These findings indicate that a novel 5-HTDRN→SOMCeA→lateral habenula pathway may mediate at least some aspects of CDS.

Fig.1 Dissection of the 5-HTDRN→SoMceA circuit combining viral tracing, optogenetic and chemogenetic methods
The researchers found an inhibitory pathway from 5-HTDRN to SOMCeA by using Cre-dependent retrograde trans-monosynaptic tracing viruses (From BrainVTA). Furthermore, optogenetic and chemogenetic viruses (From BrainVTA) were used to confirm these findings, they found that activating the 5-HTDRN→SOMCeA circuit relieved painful symptoms. These findings indicate that a novel 5-HTDRN→SOMCeA→ lateral habenula pathway may mediate at least some aspects of CDS.

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