Silent synapses dictate cocaine memory destabilization and reconsolidation.,Nature Neuroscience

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Silent synapses dictate cocaine memory destabilization and reconsolidation.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2019-12-02 , DOI: 10.1038/s41593-019-0537-6
William J Wright ₁ , Nicholas M Graziane _{1,

2} , Peter A Neumann ₁ , Peter J Hamilton ₃ , Hannah M Cates ₃ , Lauren Fuerst ₁ , Alexander Spenceley ₁ , Natalie MacKinnon-Booth ₁ , Kartik Iyer ₁ , Yanhua H Huang ₄ , Yavin Shaham ₅ , Oliver M Schlüter ₁ , Eric J Nestler ₃ , Yan Dong _{1,

4}

Affiliation

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 ~6 h 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.

中文翻译：

沉默的突触决定了可卡因记忆的不稳定和重新巩固。

与可卡因相关的记忆是持久的，但在检索时会暂时不稳定并容易受到破坏，然后会重新巩固。为了探索这些记忆动力学的突触基础，我们研究了 AMPA 受体 (AMPAR) 沉默的兴奋性突触，这些突触通过可卡因自我给药在伏隔核中产生，随后通过招募 AMPAR 在长期戒断后成熟，呼应获得和巩固可卡因记忆。我们表明，在长时间戒断后的记忆恢复中，成熟的沉默突触再次变为 AMPAR 沉默，然后在约 6 小时后重新成熟，定义了可卡因记忆不稳定窗口的开始和终止。这些突触动力学由 Rac1 计时，Rac1 活动的打开和关闭分别减少和增加，沉默的突触介导的不稳定窗口。在不稳定窗口内防止沉默的突触重新成熟会减少线索诱导的可卡因寻找。因此，可卡因产生的沉默突触构成了一个离散的突触集合，决定了可卡因相关记忆的动态，并且可以作为记忆破坏的目标。

更新日期：2019-12-02

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