Differential tonic influence of lateral habenula on prefrontal cortex and nucleus accumbens dopamine release
Differential tonic influence of lateral habenula on prefrontal cortex and nucleus accumbens dopamine release
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DOI：
10.1111/j.1460-9568.2008.06130.x
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发表时间：
2008-04-01
影响因子：
3.4
通讯作者：
Moghaddam, Bita
中科院分区：
文献类型：
--
作者：
Lecourtier, Lucas;DeFrancesco, Alicia;Moghaddam, Bita
认知或情感需求增加的条件以区域选择性的方式激活多巴胺释放。而多巴胺神经元对显著刺激的短暂毫秒反应表明多巴胺对行为的影响可能仅限于发出某些线索，多巴胺在前额叶皮层和脑桥核等区域的长期可用性与多巴胺在维持动机状态，联想学习和工作记忆中的良好作用相一致。行为引起的多巴胺终末释放通常归因于多巴胺神经元上兴奋性驱动的增加。然而，我们的研究结果表明，这种增加可能涉及主动消除对多巴胺神经元施加的侧缰（LHb）的紧张性抑制控制。抑制LHb在行为动物短暂增加多巴胺释放在前额叶皮层，背外侧纹状体核。抑制的影响是更明显的，在脑桥和纹状体比在前额叶皮层。这种模式的区域多巴胺激活LHb抑制模仿条件的奖励可用性，但不增加认知需求。电或化学刺激LHb产生最小的细胞外多巴胺的减少，这表明在清醒的大脑中，与紧张性LHb活性相关的抑制对多巴胺神经传递的影响接近最大。这些数据表明，LHb可能是至关重要的多巴胺神经元的功能差异，优先调制多巴胺神经元的项目，主要是投射到前额叶皮层的神经元，以脑桥核。
Conditions of increased cognitive or emotional demand activate dopamine release in a regionally selective manner. Whereas the brief millisecond response of dopamine neurons to salient stimuli suggests that dopamine's influence on behaviour may be limited to signalling certain cues, the prolonged availability of dopamine in regions such as the prefrontal cortex and nucleus accumbens is consistent with the well described role of dopamine in maintaining motivation states, associative learning and working memory. The behaviourally elicited terminal release of dopamine is generally attributed to increased excitatory drive on dopamine neurons. Our findings here, however, indicate that this increase may involve active removal of a tonic inhibitory control on dopamine neurons exerted by the lateral habenula (LHb). Inhibition of LHb in behaving animals transiently increased dopamine release in the prefrontal cortex, nucleus accumbens and dorsolateral striatum. The inhibitory influence was more pronounced in the nucleus accumbens and striatum than in the prefrontal cortex. This pattern of regional dopamine activation after LHb inhibition mimicked conditions of reward availability but not increased cognitive demand. Electrical or chemical stimulation of LHb produced minimal reduction of extracellular dopamine, suggesting that in an awake brain the inhibition associated with tonic LHb activity represents a near-maximal influence on dopamine neurotransmission. These data indicate that LHb may be critical for functional differences in dopamine neurons by preferentially modulating dopamine neurons that project to the nucleus accumbens over those neurons that primarily project to the prefrontal cortex.