Dual role of medial A10 dopamine neurons in affective encoding
Dual role of medial A10 dopamine neurons in affective encoding
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DOI：
10.1038/npp.2008.4
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发表时间：
2008-11-01
影响因子：
7.6
通讯作者：
Ikemoto, Satoshi
中科院分区：
文献类型：
--
作者：
Liu, Zhong-Hua;Shin, Rick;Ikemoto, Satoshi
越来越多的证据表明，内侧A10神经元的激活介导了积极的情感编码。然而，对中脑多巴胺神经元抑制的功能知之甚少。在这里，我们显示的证据表明，抑制内侧A10神经元介导的负面情感状态，导致负面的情感编码，而钝化内侧A10神经元的激活破坏积极的情感编码涉及食物奖励。我们使用了显微注射程序，其中D-2多巴胺受体激动剂quinpirole被施用到多巴胺神经元的细胞体区域，这是一种减少多巴胺细胞放电的程序。微量注射quinpirole到后内侧腹侧被盖区，但不是其更外侧的对应物，导致条件性的地方厌恶。喹吡罗管理这个网站也减少了食物摄入量和基础多巴胺浓度的腹内侧纹状体，一个主要的投射区的内侧A10神经元。此外，适度的quinpirole剂量，没有导致条件性位置厌恶或破坏食物摄入废除食物条件性位置偏好，这表明钝化多巴胺冲动活动响应食物奖励破坏积极的情感编码相关的外部刺激。我们的数据支持这一假设，即激活内侧A10多巴胺神经元介导积极的情感状态，导致积极的情感编码，而它们的抑制介导消极的情感状态，导致消极的情感编码。结合之前的研究结果，我们提出内侧A10神经元是动物学习避免负激励刺激的机制的重要组成部分。
Increasing evidence suggests that the activation of medial A10 neurons mediates positive affective encoding. However, little is known about the functions of the inhibition of midbrain dopamine neurons. Here we show evidence suggesting that the inhibition of medial A10 neurons mediates a negative affective state, leading to negative affective encoding, whereas blunting the activation of medial A10 neurons disrupts positive affective encoding involving food reward. We used a microinjection procedure, in which the D-2 dopamine receptor agonist quinpirole was administered into the cell body region of the dopamine neurons, a procedure that reduces dopamine cell firing. Microinjections of quinpirole into the posteromedial ventral tegmental area, but not its more lateral counterparts, led to conditioned place aversion. Quinpirole administration to this site also decreased food intake and basal dopamine concentration in the ventromedial striatum, a major projection area of medial A10 neurons. In addition, moderate quinpirole doses that did not lead to conditioned place aversion or disrupt food intake abolished food-conditioned place preference, suggesting that blunting dopamine impulse activity in response to food reward disrupts positive affective encoding in associated external stimuli. Our data support the hypothesis that activation of medial A10 dopamine neurons mediates a positive affective state, leading to positive affective encoding, while their inhibition mediates a negative affective state, leading to negative affective encoding. Together with previous findings, we propose that medial A10 neurons are an important component of the mechanism via which animals learn to avoid negative incentive stimuli.