Chronic Nicotine Alters Corticostriatal Plasticity in the Striatopallidal Pathway Mediated By NR2B-Containing Silent Synapses.
Chronic Nicotine Alters Corticostriatal Plasticity in the Striatopallidal Pathway Mediated By NR2B-Containing Silent Synapses.
复制标题
慢性尼古丁改变由含有 NR2B 的沉默突触介导的纹状体苍白球通路中的皮质纹状体可塑性。
DOI：
10.1038/npp.2017.87
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Beeler,JeffA
中科院分区：
文献类型：
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作者：
Xia,Jianxun;Meyers,AllisonM;Beeler,JeffA
在美国，吸烟是可预防死亡的主要原因，戒烟的成功率仍然很低。高复发率归因于普遍的尼古丁强化的激励线索的联想学习，这是高度抵抗灭绝。为什么这样的学习是如此持久尚不清楚，但可能是由于长期尼古丁诱导的突触可塑性的神经适应。采用全细胞膜片钳记录的方法研究了慢性尼古丁（cNIC）对背外侧纹状体间接纹状体通路中表达多巴胺D2受体的中棘神经元突触可塑性的影响。暴露于cNIC的小鼠对高频刺激的反应表现出长期增强，而不是预期的抑郁。cNIC降低了基线AMPA/NMDA比率，这是由于NR2B亚基富集的NMDA电流增加，同时上调了仅NMDA的沉默突触。这些数据表明，正如可卡因和阿片类药物所观察到的那样，cNIC可以增加msn中的沉默突触，并改变皮质纹状体可塑性的调节。先前的研究表明，可卡因和吗啡诱导的腹侧纹状体沉默突触的上调；我们发现它可以发生在背纹状体，这一区域与成瘾、渴望和线索诱导的复发有关。
Smoking is the leading cause of preventable death in the United States and success rates for quitting remain low. High relapse rates are attributed to pervasive nicotine-reinforced associative learning of incentive cues that is highly resistant to extinction. Why such learning is so persistent is poorly understood but may arise as a consequence of neuroadaptations in synaptic plasticity induced by chronic nicotine. We used whole-cell patch clamp recording to investigate the effect of chronic nicotine (cNIC) on synaptic plasticity in dopamine D2 receptor-expressing medium-spiny neurons in the indirect, striatopallidal pathway in dorsolateral striatum. Mice exposed to cNIC exhibited long-term potentiation in response to high-frequency stimulation instead of the expected depression. cNIC decreased baseline AMPA/NMDA ratio, arising from increased NMDA currents enriched in the NR2B subunit with a concomitant upregulation of NMDA-only, silent synapses. These data demonstrate that cNIC can increase silent synapses in MSNs, as observed with cocaine and opiates, and alter the regulation of corticostriatal plasticity. Prior work has characterized cocaine-and morphine-induced upregulation of silent synapses in the ventral striatum; we show it can occur in the dorsal striatum, a region associated with later stages of addiction, craving, and cue-induced relapse.