美国匹兹堡大学Yan Dong研究团队发现，沉默突触决定可卡因记忆的不稳定和重新整合。该研究2019年12月2日在线发表在国际学术期刊《自然—神经科学》上。

为了探索这些记忆动力学的突触基础，课题组研究了可卡因自我给药在伏隔核中产生的AMPA受体（AMPAR）沉默兴奋性突触，以及长期断药后，通过招募AMPARs、回声采集和可卡因记忆巩固后的逐渐成熟。他们表示，在长期断药后的记忆恢复中，成熟的沉默突触再次变为AMPAR沉默，然后在约6h后重新成熟，定义了可卡因记忆失稳窗口的发生和终止。这些突触动力学是由Rac1定时的，Rac1活性的降低和升高分别打开和关闭沉默突触介导的去稳定窗口。防止在不稳定窗口内沉默突触再成熟会降低环境诱导的可卡因记忆搜寻。因此，可卡因产生的沉默突触构成决定可卡因相关记忆动力学的离散突触集合，并且可以作为记忆破坏的目标。

据悉，可卡因相关的记忆是持久性的，但是一旦恢复，它们就会暂时不稳定并容易受到破坏，然后重新整合。

附：英文原文

Title: Silent synapses dictate cocaine memory destabilization and reconsolidation

Author: William J. Wright, Nicholas M. Graziane, Peter A. Neumann, Peter J. Hamilton, Hannah M. Cates, Lauren Fuerst, Alexander Spenceley, Natalie MacKinnon-Booth, Kartik Iyer, Yanhua H. Huang, Yavin Shaham, Oliver M. Schlter, Eric J. Nestler, Yan Dong

Issue&Volume: 2019-12-02

Abstract: Cocaine-associated memories are persistent, but, on retrieval, become temporarily destabilized and vulnerable to disruptions, followed by reconsolidation. To explore the synaptic underpinnings for these memory dynamics, we studied AMPA receptor (AMPAR)-silent excitatory synapses, which are generated in the nucleus accumbens by cocaine self-administration, and subsequently mature after prolonged withdrawal by recruiting AMPARs, echoing acquisition and consolidation of cocaine memories. We show that, on memory retrieval after prolonged withdrawal, the matured silent synapses become AMPAR-silent again, followed by re-maturation ~6h later, defining the onset and termination of a destabilization window of cocaine memories. These synaptic dynamics are timed by Rac1, with decreased and increased Rac1 activities opening and closing, respectively, the silent synapse-mediated destabilization window. Preventing silent synapse re-maturation within the destabilization window decreases cue-induced cocaine seeking. Thus, cocaine-generated silent synapses constitute a discrete synaptic ensemble dictating the dynamics of cocaine-associated memories and can be targeted for memory disruption.

DOI: 10.1038/s41593-019-0537-6

Source: https://www.nature.com/articles/s41593-019-0537-6