Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway.
Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway.
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腹侧苍白球 GABA 能神经元通过腹侧被盖通路控制与动机相关的觉醒
DOI：
10.1038/s41380-020-00906-0
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发表时间：
2021-07
影响因子：
11
通讯作者：
Huang ZL
中科院分区：
文献类型：
--
作者：
Li YD;Luo YJ;Xu W;Ge J;Cherasse Y;Wang YQ;Lazarus M;Qu WM;Huang ZL
腹侧苍白球（VP）调节动机、毒瘾和一些依赖于高度兴奋的行为。然而，VP 在控制觉醒中的作用和潜在的神经回路仍然知之甚少。在本研究中，我们试图阐明 VP GABA 能神经元在控制小鼠睡眠-觉醒行为中的具体作用。纤维光度测定显示，在从非快速动眼睡眠（非快速眼动睡眠，NREM）睡眠到清醒或快速眼动睡眠的生理转变过程中，VP GABA 能神经元的群体活动增加。此外，利用化学遗传学和光遗传学操作来研究 VP GABA 能神经元在启动和/或维持唤醒中的潜在因果作用。对支配腹侧被盖区 (VTA) 的 VP GABA 能神经元进行体内光遗传学刺激，通过解除 VTA 多巴胺能神经元的抑制，强烈促进觉醒。功能性体外图谱显示，VP GABA 能神经元原则上抑制 VTA GABA 能神经元，但也抑制 VTA 多巴胺能神经元。此外，对 VP GABA 能神经元末端的光遗传学刺激表明，它们通过支配外侧下丘脑而不是内侧丘脑或外侧缰核来促进觉醒。通过多巴胺能 D1 和 D2/D3 受体拮抗剂预处理，VP GABA 能神经元激活化学遗传学引起的觉醒增加被完全消除。此外，VP GABA能神经元的激活增加了开放场和明暗盒测试中的探索时间，但没有调节抑郁样行为或食物摄入。最后，VP GABA 能神经元的化学遗传学抑制降低了觉醒。总而言之，我们的研究结果表明 VP GABA 能神经元对于与动机相关的唤醒至关重要。
The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1and D2/D3receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.
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影响因子：
16.2
作者：
Creed M;Ntamati NR;Chandra R;Lobo MK;Lüscher C
通讯作者：
Lüscher C
伏隔核通过表达多巴胺 D1 受体的神经元亚群控制觉醒
影响因子：
16.6
作者：
Luo YJ;Li YD;Wang L;Yang SR;Yuan XS;Wang J;Cherasse Y;Lazarus M;Chen JF;Qu WM;Huang ZL
通讯作者：
Huang ZL
影响因子：
16.6
作者：
Faget L;Zell V;Souter E;McPherson A;Ressler R;Gutierrez-Reed N;Yoo JH;Dulcis D;Hnasko TS
通讯作者：
Hnasko TS
影响因子：
16.6
作者：
Anaclet C;Pedersen NP;Ferrari LL;Venner A;Bass CE;Arrigoni E;Fuller PM
通讯作者：
Fuller PM
影响因子：
25
作者：
Eban-Rothschild A;Rothschild G;Giardino WJ;Jones JR;de Lecea L
通讯作者：
de Lecea L