Fear extinction memory consolidation requires potentiation of pontine-wave activity during REM sleep.
Fear extinction memory consolidation requires potentiation of pontine-wave activity during REM sleep.
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DOI：
10.1523/jneurosci.5525-12.2013
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发表时间：
2013-03-06
期刊：
影响因子：
--
通讯作者：
O'Malley MW
中科院分区：
文献类型：
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作者：
Datta S;O'Malley MW
睡眠在包括情境恐惧消退记忆在内的多个记忆系统的记忆巩固中起着重要作用，但人们对这一过程的机制知之甚少。在这里，我们展示了在老鼠身上进行的恐惧消除训练，消除了条件性恐惧，增加了慢波睡眠和快速眼动（REM）睡眠。令人惊讶的是，24小时后，在记忆测试中，只有57%的恐惧消失的动物保留了恐惧消失的记忆。我们发现，这些动物在训练后的快速眼动睡眠中表现出相脑波（p波）活动的增加，而在43%未能保留恐惧消退记忆的动物中没有这种活动。本研究的结果证明，在训练后的快速眼动睡眠期间，脑干的激活，特别是相p波活动的增强，对巩固恐惧消退记忆至关重要。这项研究的结果还表明，与普遍的睡眠和记忆的假设相反，仅仅在训练后增加睡眠并不能保证恐惧消退记忆的巩固和/或保留。相反，特定的睡眠依赖生理事件的增强可能是成功巩固恐惧消退记忆的更准确的预测因素。识别这种独特的机制将显著提高我们目前对情绪记忆的睡眠依赖调节的细胞和分子机制的理解。此外，这一发现也可能开启一种新的、更有针对性的治疗人类恐惧和焦虑临床障碍的方法的开发，这种方法比现有的方法更有效，比如只结合恐惧消除的暴露疗法。
Sleep plays an important role in memory consolidation within multiple memory systems including contextual fear extinction memory, but little is known about the mechanisms that underlie this process. Here, we show that fear extinction training in rats, which extinguished conditioned fear, increased both slow-wave sleep and rapid-eye movement (REM) sleep. Surprisingly, 24 h later, during memory testing, only 57% of the fear-extinguished animals retained fear extinction memory. We found that these animals exhibited an increase in phasic pontine-wave (P-wave) activity during post-training REM sleep, which was absent in the 43% of animals that failed to retain fear extinction memory. The results of this study provide evidence that brainstem activation, specifically potentiation of phasic P-wave activity, during post-training REM sleep is critical for consolidation of fear extinction memory. The results of this study also suggest that, contrary to the popular hypothesis of sleep and memory, increased sleep after training alone does not guarantee consolidation and/or retention of fear extinction memory. Rather, the potentiation of specific sleep-dependent physiological events may be a more accurate predictor for successful consolidation of fear extinction memory. Identification of this unique mechanism will significantly improve our present understanding of the cellular and molecular mechanisms that underlie the sleep-dependent regulation of emotional memory. Additionally, this discovery may also initiate development of a new, more targeted treatment method for clinical disorders of fear and anxiety in humans that is more efficacious than existing methods such as exposure therapy that incorporate only fear extinction.