Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear
Increasing CREB in the auditory thalamus enhances memory and generalization of auditory conditioned fear
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DOI：
10.1101/lm.993608
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发表时间：
2008-06-01
影响因子：
2
通讯作者：
Josselyn, Sheena A.
中科院分区：
文献类型：
--
作者：
Han, Jin-Hee;Yiu, Adelaide P.;Josselyn, Sheena A.
虽然杏仁核（LA）的外侧核是必不可少的条件听觉恐惧记忆，一个新兴的主题是，在多个大脑区域的可塑性有助于恐惧记忆的形成。LA接受来自听觉丘脑的直接投射，特别是内侧膝状体核（MGm）的内侧部和相邻的后板内核（PIN）。虽然传统上被认为是一个简单的中继结构，越来越多的证据表明丘脑在不同的认知过程。我们研究了听觉恐惧记忆中MGm/PIN的可塑性作用。首先，我们发现听觉恐惧条件反射（但不是控制操作）增加了激活CREB在MGm和PIN的水平。接下来，使用病毒载体，我们表明，外源性增加CREB在这个区域特别增强了听觉条件恐惧记忆的形成，而不影响听觉恐惧记忆的表达，背景恐惧记忆的形成，或基本的听觉处理。有趣的是，MGm/PIN中CREB水平增加的小鼠也表现出广泛的听觉恐惧泛化（与对照小鼠相比，它们对其他频率的音调表现出恐惧反应）。总之，这些结果暗示CREB介导的可塑性在MGm/PIN的条件听觉恐惧记忆的形成和泛化。这些发现不仅完善了我们对恐惧记忆回路的认识，而且还提供了新的见解，让我们了解神经基质在多大程度上控制着对一种音调的习得性恐惧推广到其他音调。
Although the lateral nucleus of the amygdala (LA) is essential for conditioned auditory fear memory, an emerging theme is that plasticity in multiple brain regions contributes to fear memory formation. The LA receives direct projections from the auditory thalamus, specifically the medial division of the medial geniculate nucleus (MGm) and adjacent posterior intralaminar nucleus (PIN). While traditionally viewed as a simple relay structure, mounting evidence implicates the thalamus in diverse cognitive processes. We investigated the role of plasticity in the MGm/PIN in auditory fear memory. First we found that auditory fear conditioning (but not control manipulations) increased the levels of activated CREB in both the MGm and PIN. Next, using viral vectors, we showed that exogenously increasing CREB in this region specifically enhanced formation of an auditory conditioned fear memory without affecting expression of an auditory fear memory, formation of a contextual fear memory, or basic auditory processing. Interestingly, mice with increased CREB levels in the MGm/PIN also showed broad auditory fear generalization (in contrast to control mice, they exhibited fear responses to tones of other frequencies). Together, these results implicate CREB-mediated plasticity in the MGm/PIN in both the formation and generalization of conditioned auditory fear memory. Not only do these findings refine our knowledge of the circuitry underlying fear memory but they also provide novel insights into the neural substrates that govern the degree to which acquired fear of a tone generalizes to other tones.