Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior
Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior
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DOI：
10.1038/nn.4482
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发表时间：
2017-03-01
影响因子：
25
通讯作者：
Bonci, Antonello
中科院分区：
文献类型：
--
作者：
Edwards, Nicholas J.;Tejeda, Hugo A.;Bonci, Antonello
腹侧被盖区（VTA）的传入输入通过调节多巴胺神经元的活动来控制奖赏相关行为。延髓核（NAc）提供了一个最突出的预测腹侧被盖区，然而，最近的研究提供了相互矛盾的证据，这些抑制性输入的功能。利用光遗传学，细胞特异性消融，全细胞膜片钳和免疫电镜，我们发现，NAc输入突触直接到多巴胺神经元，优先激活GABA（B）受体。来自NAc和局部VTA GABA神经元的GABA能输入在多巴胺神经元中被差异调制和激活单独的受体群体。成年小鼠多巴胺神经元GABA（B）受体的基因缺失不影响一般或吗啡诱导的运动活动，但显着增加可卡因诱导的运动。总的来说，我们的研究结果表明腹侧被盖区的抑制结构具有显著的选择性，并表明多巴胺神经元的长距离GABA能输入从根本上调节对可卡因的行为反应。
Afferent inputs to the ventral tegmental area (VTA) control reward-related behaviors through regulation of dopamine neuron activity. The nucleus accumbens (NAc) provides one of the most prominent projections to the VTA; however, recent studies have provided conflicting evidence regarding the function of these inhibitory inputs. Using optogenetics, cell-specific ablation, whole cell patch clamp and immuno-electron microscopy, we found that NAc inputs synapsed directly onto dopamine neurons, preferentially activating GABA(B) receptors. GABAergic inputs from the NAc and local VTA GABA neurons were differentially modulated and activated separate receptor populations in dopamine neurons. Genetic deletion of GABA(B) receptors from dopamine neurons in adult mice did not affect general or morphine-induced locomotor activity, but markedly increased cocaine-induced locomotion. Collectively, our findings demonstrate notable selectivity in the inhibitory architecture of the VTA and suggest that long-range GABAergic inputs to dopamine neurons fundamentally regulate behavioral responses to cocaine.