A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System
A Neural Circuit Mechanism for Encoding Aversive Stimuli in the Mesolimbic Dopamine System
复制标题
DOI：
10.1016/j.neuron.2018.11.005
复制
发表时间：
2019-01-02
期刊：
影响因子：
16.2
通讯作者：
Lammel, Stephan
中科院分区：
文献类型：
--
作者：
de Jong, Johannes W.;Afjei, Seyedeh Atiyeh;Lammel, Stephan
腹侧被盖区（VTA）多巴胺（DA）神经元在调节动机行为中起着核心作用，但它们发出积极和消极动机刺激信号的电路尚不完全清楚。使用体内纤维光度法，我们同时记录了在厌恶和奖励条件反射任务中不同伏隔核（NAc）亚核DA终端的活动。我们发现，腹侧NAc内侧壳（vNAcMed）的DA终端对意想不到的厌恶结果和预测它们的线索感到兴奋，而其他NAc亚区的DA终端则持续低迷。对奖励预测线索的兴奋在NAc侧壳中占主导地位，而在vNAcMed中基本不存在。此外，我们证明了下丘脑外侧的谷氨酸能（表达vglut2）神经元是向vnacmed -投射的DA神经元提供厌恶结果信息的关键传入输入。总的来说，我们揭示了不同的中脑边缘数据处理子系统的不同功能贡献及其驱动行为的传入通路。
Ventral tegmental area (VTA) dopamine (DA) neurons play a central role in mediating motivated behaviors, but the circuitry through which they signal positive and negative motivational stimuli is incompletely understood. Using in vivo fiber photometry, we simultaneously recorded activity in DA terminals in different nucleus accumbens (NAc) subnuclei during an aversive and reward conditioning task. We find that DA terminals in the ventral NAc medial shell (vNAcMed) are excited by unexpected aversive outcomes and to cues that predict them, whereas DA terminals in other NAc subregions are persistently depressed. Excitation to reward-predictive cues dominated in the NAc lateral shell and was largely absent in the vNAcMed. Moreover, we demonstrate that glutamatergic (VGLUT2-expressing) neurons in the lateral hypothalamus represent a key afferent input for providing information about aversive outcomes to vNAcMed-projecting DA neurons. Collectively, we reveal the distinct functional contributions of separate mesolimbic DA subsystems and their afferent pathways underlying motivated behaviors.