The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons.
The laterodorsal tegmentum-ventral tegmental area circuit controls depression-like behaviors by activating ErbB4 in DA neurons.
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DOI：
10.1038/s41380-021-01137-7
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发表时间：
2023-03
影响因子：
11
通讯作者：
Mei L
中科院分区：
文献类型：
--
作者：
Wang H;Cui W;Chen W;Liu F;Dong Z;Xing G;Luo B;Gao N;Zou WJ;Zhao K;Zhang H;Ren X;Yu Z;Robinson HL;Liu Z;Xiong WC;Mei L
腹侧被盖区（VTA）的多巴胺（DA）神经元对应对压力至关重要。然而，调节其活性和应激诱导的抑郁症的分子机制还没有得到很好的理解。我们发现，VTA中的受体酪氨酸激酶ErbB 4在应激敏感小鼠中被激活。删除腹侧被盖区或多巴胺能神经元中的ErbB 4，或化学遗传抑制腹侧被盖区ErbB 4激酶活性，抑制慢性社会失败压力（CSDS）诱导的抑郁样行为的发展。ErbB 4激活需要NRG 1在背侧被盖（LDTg）的表达; LDTg特异性缺失NRG 1抑制抑郁样行为。NRG 1和ErbB 4抑制腹侧被盖区DA能神经元的钾电流，并增加其放电活动。最后，我们发现应激后急性抑制ErbB 4可减弱DA神经元的过度活跃和抑郁样行为的表达。总之，这些观察结果表明NRG 1-ErbB 4信号在调节抑郁样行为中的关键作用，并确定了LDTg-VTA回路调节DA神经元活性的意外机制。
Dopamine (DA) neurons in the ventral tegmental area (VTA) are critical to coping with stress. However, molecular mechanisms regulating their activity and stress-induced depression were not well understood. We found that the receptor tyrosine kinase ErbB4 in VTA was activated in stress-susceptible mice. Deleting ErbB4 in VTA or in DA neurons, or chemical genetic inhibition of ErbB4 kinase activity in VTA suppressed the development of chronic social defeat stress (CSDS)-induced depression-like behaviors. ErbB4 activation required the expression of NRG1 in the laterodorsal tegmentum (LDTg); LDTg-specific deletion of NRG1 inhibited depression-like behaviors. NRG1 and ErbB4 suppressed potassium currents of VTA DA neurons and increased their firing activity. Finally, we showed that acute inhibition of ErbB4 after stress attenuated DA neuron hyperactivity and expression of depression-like behaviors. Together, these observations demonstrate a critical role of NRG1-ErbB4 signaling in regulating depression-like behaviors and identify an unexpected mechanism by which the LDTg-VTA circuit regulates the activity of DA neurons.
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影响因子：
6.8
作者：
Biernacka JM;Sangkuhl K;Jenkins G;Whaley RM;Barman P;Batzler A;Altman RB;Arolt V;Brockmöller J;Chen CH;Domschke K;Hall-Flavin DK;Hong CJ;Illi A;Ji Y;Kampman O;Kinoshita T;Leinonen E;Liou YJ;Mushiroda T;Nonen S;Skime MK;Wang L;Baune BT;Kato M;Liu YL;Praphanphoj V;Stingl JC;Tsai SJ;Kubo M;Klein TE;Weinshilboum R
通讯作者：
Weinshilboum R
影响因子：
5.3
作者：
Bean, Jonathan C.;Lin, Thiri W.;Mei, Lin
通讯作者：
Mei, Lin
DOI：
10.1101/lm.040253.115
发表时间：
2016-04
期刊：
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子：
--
作者：
Dulka BN;Ford EC;Lee MA;Donnell NJ;Goode TD;Prosser R;Cooper MA
通讯作者：
Cooper MA
影响因子：
1.2
作者：
Dougalis，Antonios G.;Matthews，Gillian A. C.;Ungless，Mark A.
通讯作者：
Ungless，Mark A.
杏仁核 NRG1-ErbB4 对于调节焦虑样行为至关重要。
影响因子：
7.6
作者：
Bi, Lin-Lin;Sun, Xiang-Dong;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming