Neurosciences Graduate Program, Stanford University, Stanford, CA 94305, USA.
Shenzhen Key Laboratory of Drug Addiction, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China.
Neuron. 2020 Sep 23;107(6):1113-1123.e4. doi: 10.1016/j.neuron.2020.06.028. Epub 2020 Jul 16.
Disrupting memories that associate environmental cues with drug experiences holds promise for treating addiction, yet accessing the distributed neural network that stores such memories is challenging. Here, we show that the paraventricular nucleus of the thalamus (PVT) orchestrates the acquisition and maintenance of opiate-associated memories via projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). PVT→CeA activity associates morphine reward to the environment, whereas transient inhibition of the PVT→NAc pathway during retrieval causes enduring protection against opiate-primed relapse. Using brain-wide activity mapping, we revealed distributed network activities that are altered in non-relapsing mice, which enabled us to find that activating the downstream NAc→lateral hypothalamus (LH) pathway also prevents relapse. These findings establish the PVT as a key node in the opiate-associated memory network and demonstrate the potential of targeting the PVT→NAc→LH pathway for treating opioid addiction.
破坏将环境线索与药物体验相关联的记忆有望治疗成瘾，但访问存储此类记忆的分布式神经网络具有挑战性。在这里，我们表明丘脑室旁核 (PVT) 通过投射到杏仁核中央核 (CeA) 和伏隔核 (NAc) 来协调阿片类药物相关记忆的获得和维持。PVT→CeA 活动将吗啡奖励与环境相关联，而在检索过程中短暂抑制 PVT→NAc 通路会导致对阿片类药物引发的复发性持久保护。使用全脑活动映射，我们揭示了在非复发小鼠中改变的分布式网络活动，这使我们能够发现激活下游 NAc→外侧下丘脑 (LH) 通路也可以预防复发。这些发现确立了 PVT 作为阿片类药物相关记忆网络中的关键节点，并证明了靶向 PVT→NAc→LH 通路治疗阿片类药物成瘾的潜力。
