Activin plays a key role in the maintenance of long-term memory and late-LTP
Activin plays a key role in the maintenance of long-term memory and late-LTP
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DOI：
10.1101/lm.16659010
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发表时间：
2010-04-01
影响因子：
2
通讯作者：
Inokuchi, Kaoru
中科院分区：
文献类型：
--
作者：
Ageta, Hiroshi;Ikegami, Shiro;Inokuchi, Kaoru
最近的一项研究表明，恐惧记忆可能在检索后变得脆弱，然后以蛋白质合成依赖的方式重新巩固。然而，对这些过程的分子机制知之甚少。激活素β A是tgf - β超家族的一员，在激活的神经元回路中增加，并调节树突棘形态。为了阐明激活素在成人大脑突触可塑性中的作用，我们研究了抑制或增强激活素功能对海马长期增强（LTP）的影响。我们发现卵泡抑素，一种激活素的特异性抑制剂，阻断了海马中晚期LTP （L-LTP）的维持。相反，激活素有助于维持早期LTP （E-LTP）。我们产生了前脑特异性激活素或卵泡抑素转基因小鼠，其中转基因表达在Tet-OFF系统的控制下。卵泡抑素转基因小鼠海马L-LTP的维持被阻断。在情境恐惧条件反射测试中，我们发现卵泡抑素阻断了长期记忆的形成，但不影响短期记忆的形成。此外，follistatin的表达在检索期间选择性地削弱了巩固记忆，而在维持阶段则没有。另一方面，激活素在检索阶段的过度表达也会影响记忆的维持。因此，在检索阶段，大脑中的激活素水平在长期记忆的维持中起着关键作用。
A recent study has revealed that fear memory may be vulnerable following retrieval, and is then reconsolidated in a protein synthesis-dependent manner. However, little is known about the molecular mechanisms of these processes. Activin beta A, a member of the TGF-beta superfamily, is increased in activated neuronal circuits and regulates dendritic spine morphology. To clarify the role of activin in the synaptic plasticity of the adult brain, we examined the effect of inhibiting or enhancing activin function on hippocampal long-term potentiation (LTP). We found that follistatin, a specific inhibitor of activin, blocked the maintenance of late LTP (L-LTP) in the hippocampus. In contrast, administration of activin facilitated the maintenance of early LTP (E-LTP). We generated forebrain-specific activin-or follistatin-transgenic mice in which transgene expression is under the control of the Tet-OFF system. Maintenance of hippocampal L-LTP was blocked in the follistatin-transgenic mice. In the contextual fear-conditioning test, we found that follistatin blocked the formation of long-term memory (LTM) without affecting short-term memory (STM). Furthermore, consolidated memory was selectively weakened by the expression of follistatin during retrieval, but not during the maintenance phase. On the other hand, the maintenance of memory was also influenced by activin overexpression during the retrieval phase. Thus, the level of activin in the brain during the retrieval phase plays a key role in the maintenance of long-term memory.