The Formation of Recent and Remote Memory Is Associated with Time-Dependent Formation of Dendritic Spines in the Hippocampus and Anterior Cingulate Cortex
The Formation of Recent and Remote Memory Is Associated with Time-Dependent Formation of Dendritic Spines in the Hippocampus and Anterior Cingulate Cortex
复制标题
DOI：
10.1523/jneurosci.0966-09.2009
复制
发表时间：
2009-06-24
影响因子：
5.3
通讯作者：
Ammassari-Teule, Martine
中科院分区：
文献类型：
--
作者：
Restivo, Leonardo;Vetere, Gisella;Ammassari-Teule, Martine
尽管海马区-大脑皮层的相互作用对于形成持久的陈述性记忆至关重要，但支配长期记忆存储的突触事件大多仍不清楚。我们提出的证据表明，在形成近期和远程情景恐惧记忆的过程中，神经元结构的变化，即树突棘的生长，在海马区和前扣带回皮质(ACC)依次发展。我们发现，当小鼠在条件反射后24小时或36天回到实验情境中时，被放置在条件反射室内7分钟的条件反射室内，暴露于5次足电击(持续时间，2 S；强度，0.7 mA；刺激间间隔，60 S)下，小鼠在条件反射24小时或36天后表现出强烈的恐惧反应。然后我们观察到，在最近的时间点，而不是遥远的时间点，他们的恐惧反应与海马神经元上脊柱密度的增加有关，而在ACC神经元上发生了相反的时间模式的脊柱密度变化。在每个时间点，即使在没有最近或远程记忆测试的情况下，海马体或ACC的结构也发生了变化，因此表明它们不是由提取过程驱动的。此外，在条件化处理后立即进行海马区ibotenic损毁会损害远距离记忆，并阻止ACC神经元上树突棘的生长，而在24天后进行这些损毁则无效。这些发现揭示了逐渐的结构变化改变了海马-皮质网络的连通性，构成了远程记忆的形成和表达的基础，而且海马体在驱动皮质结构可塑性方面发挥着关键但有时间限制的作用。
Although hippocampal-cortical interactions are crucial for the formation of enduring declarative memories, synaptic events that govern long-term memory storage remain mostly unclear. We present evidence that neuronal structural changes, i.e., dendritic spine growth, develop sequentially in the hippocampus and anterior cingulate cortex (aCC) during the formation of recent and remote contextual fear memory. We found that mice placed in a conditioning chamber for one 7 min conditioning session and exposed to five footshocks (duration, 2 s; intensity, 0.7 mA; interstimulus interval, 60 s) delivered through the grid floor exhibited robust fear response when returned to the experimental context 24 h or 36 d after the conditioning. We then observed that their fear response at the recent, but not the remote, time point was associated with an increase in spine density on hippocampal neurons, whereas an inverse temporal pattern of spine density changes occurred on aCC neurons. At each time point, hippocampal or aCC structural alterations were achieved even in the absence of recent or remote memory tests, thus suggesting that they were not driven by retrieval processes. Furthermore, ibotenic lesions of the hippocampus impaired remote memory and prevented dendritic spine growth on aCC neurons when they were performed immediately after the conditioning, whereas they were ineffective when performed 24 d later. These findings reveal that gradual structural changes modifying connectivity in hippocampal-cortical networks underlie the formation and expression of remote memory, and that the hippocampus plays a crucial but time-limited role in driving structural plasticity in the cortex.