National Institute of Biological Sciences (NIBS), Beijing 102206, China.
National Institute of Biological Sciences (NIBS), Beijing 102206, China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Neuron. 2020 May 6;106(3):498-514.e8. doi: 10.1016/j.neuron.2020.02.009. Epub 2020 Mar 6.
The brain dopamine (DA) system participates in forming and expressing memory. Despite a well-established role of DA neurons in the ventral tegmental area in memory formation, the exact DA circuits that control memory expression remain unclear. Here, we show that DA neurons in the dorsal raphe nucleus (DRN) and their medulla input control the expression of incentive memory. DRN DA neurons are activated by both rewarding and aversive stimuli in a learning-dependent manner and exhibit elevated activity during memory recall. Disrupting their physiological activity or DA synthesis blocks the expression of natural appetitive and aversive memories as well as drug memories associated with opioids. Moreover, a glutamatergic pathway from the lateral parabrachial nucleus to the DRN selectively regulates the expression of reward memories associated with opioids or foods. Our study reveals a specialized DA subsystem important for memory expression and suggests new targets for interventions against opioid addiction.
大脑多巴胺(DA)系统参与形成和表达记忆。尽管腹侧被盖区(VTA)中的 DA 神经元在记忆形成中起着公认的作用,但控制记忆表达的确切 DA 回路仍不清楚。在这里,我们表明中缝核(DRN)中的 DA 神经元及其延髓输入控制着奖励记忆的表达。DRN DA 神经元以学习依赖的方式被奖励和惩罚性刺激激活,并在记忆回忆期间表现出更高的活性。破坏其生理活性或 DA 合成会阻止自然的奖赏和惩罚记忆以及与阿片类药物相关的药物记忆的表达。此外,来自外侧臂旁核到 DRN 的谷氨酸能通路选择性地调节与阿片类药物或食物相关的奖赏记忆的表达。我们的研究揭示了一个重要的专门的 DA 子系统,该系统对记忆表达很重要,并为干预阿片类药物成瘾提供了新的靶点。