VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release.
VTA Glutamate Neuron Activity Drives Positive Reinforcement Absent Dopamine Co-release.
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DOI：
10.1016/j.neuron.2020.06.011
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发表时间：
2020-09-09
期刊：
影响因子：
16.2
通讯作者：
Hnasko TS
中科院分区：
文献类型：
--
作者：
Zell V;Steinkellner T;Hollon NG;Warlow SM;Souter E;Faget L;Hunker AC;Jin X;Zweifel LS;Hnasko TS
腹侧被盖区（VTA）多巴胺（DA）神经元一样，腹侧被盖区谷氨酸神经元的活动可以支持正强化。然而，一个子集的腹侧被盖区神经元共同释放DA和谷氨酸，DA的释放可能是负责行为强化诱导腹侧被盖区谷氨酸神经元的活动。为了测试这一点，我们使用光遗传学来刺激VTA谷氨酸神经元，其中使用floxed Th小鼠或基于病毒的CRISPR/Cas9有条件地消融酪氨酸羟化酶（TH），从而DA生物合成。这两种方法都导致VTA谷氨酸神经元TH表达的丧失，以及延髓核（NAc）中DA从其远端终末释放的丧失。尽管DA信号的损失，光遗传学激活腹侧被盖区谷氨酸细胞体或轴突末梢在NAc足以支持加固。这些结果表明，谷氨酸释放VTA是足以促进独立的伴随DA共释放的强化，建立一个非DA的机制，VTA活动可以支持奖励寻求行为。腹侧被盖区谷氨酸神经元的激活导致多巴胺在延髓核中的共同释放。策尔等人通过基因阻断这种多巴胺信号，证明腹侧被盖区谷氨酸投射到丘脑核可以独立地强化行为。这些发现建立了一个能够支持正强化的平行多巴胺非依赖性中边缘通路。
Like ventral tegmental area (VTA) dopamine (DA) neurons, VTA glutamate neuron activity can support positive reinforcement. However, a subset of VTA neurons co-release DA and glutamate, and DA release may be responsible for behavioral reinforcement induced by VTA glutamate neuron activity. To test this, we used optogenetics to stimulate VTA glutamate neurons in which tyrosine hydroxylase (TH), and thus DA biosynthesis, was conditionally ablated using either floxed Th mice or viral-based CRISPR/Cas9. Both approaches led to loss of TH expression in VTA glutamate neurons, and loss of DA release from their distal terminals in nucleus accumbens (NAc). Despite loss of the DA signal, optogenetic activation of VTA glutamate cell bodies or axon terminals in NAc was sufficient to support reinforcement. These results suggest that glutamate release from VTA is sufficient to promote reinforcement independent of concomitant DA co-release, establishing a non-DA mechanism by which VTA activity can support reward-seeking behaviors. Activation of VTA glutamate neurons leads to dopamine co-release in nucleus accumbens. Zell et al. genetically block this dopamine signal to show that VTA glutamate projections to nucleus accumbens can reinforce behaviors independently. These findings establish a parallel dopamine-independent mesolimbic pathway capable of supporting positive reinforcement.
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影响因子：
5
作者：
Keithley, Richard B.;Wightman, R. Mark
通讯作者：
Wightman, R. Mark
影响因子：
16.2
作者：
Chuhma N;Mingote S;Moore H;Rayport S
通讯作者：
Rayport S
影响因子：
18.2
作者：
Hnasko TS;Edwards RH
通讯作者：
Edwards RH
DOI：
10.1073/pnas.0910986107
发表时间：
2010-01-05
影响因子：
11.1
作者：
Birgner, Carolina;Nordenankar, Karin;Wallen-Mackenzie, Asa
通讯作者：
Wallen-Mackenzie, Asa
影响因子：
16.2
作者：
Hnasko, Thomas S.;Chuhma, Nao;Zhang, Hui;Goh, Germaine Y.;Sulzer, David;Palmiter, Richard D.;Rayport, Stephen;Edwards, Robert H.
通讯作者：
Edwards, Robert H.