Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus.
Dopamine Regulates Aversive Contextual Learning and Associated In Vivo Synaptic Plasticity in the Hippocampus.
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DOI：
10.1016/j.celrep.2016.01.070
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发表时间：
2016-03-01
期刊：
影响因子：
8.8
通讯作者：
Dani JA
中科院分区：
文献类型：
--
作者：
Broussard JI;Yang K;Levine AT;Tsetsenis T;Jenson D;Cao F;Garcia I;Arenkiel BR;Zhou FM;De Biasi M;Dani JA
奖赏驱动行为中的多巴胺释放影响突触的可塑性。然而，多巴胺在海马区的神经支配和释放及其在厌恶行为中的作用仍存在争议。在这里，我们表明在体内海马区CA3-CA1回路的突触可塑性是抑制回避(IA)训练中上下文学习的基础。免疫组织化学和分子技术证实了来自中脑的稀疏多巴胺能神经支配海马体。用D_1样多巴胺受体激动剂或拮抗剂在体外和在自由活动小鼠的海马片上评估了支持IA学习的长期突触增强(LTP)。抑制D1样多巴胺受体损害了IA任务的记忆，并阻止了训练诱导的体外和体内LTP诱导的增强。结果表明，在厌恶的情境任务中，多巴胺受体信号调节厌恶记忆的保持，并调节海马体中可能构成学习基础的相关突触机制。
Dopamine release during reward-driven behaviors influences synaptic plasticity. However, dopamine innervation and release in the hippocampus and its role during aversive behaviors are controversial. Here we show that in vivo hippocampal synaptic plasticity in the CA3-CA1 circuit underlies contextual learning during inhibitory avoidance (IA) training. Immunohistochemistry and molecular techniques verified sparse dopaminergic innervation of the hippocampus from the midbrain. The long-term synaptic potentiation (LTP) underlying the learning of IA was assessed with a D1-like dopamine receptor agonist or antagonist in ex vivo hippocampal slices and in vivo in freely-moving mice. Inhibition of D1-like dopamine receptors impaired memory of the IA task and prevented the training-induced enhancement of both ex vivo and in vivo LTP induction. The results indicate that dopamine-receptor signaling during an aversive contextual task regulates aversive memory retention and regulates associated synaptic mechanisms in the hippocampus that likely underlie learning.