Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-3800, USA.
Neurobiol Learn Mem. 2012 Mar;97(3):313-20. doi: 10.1016/j.nlm.2012.02.004. Epub 2012 Feb 27.
Past studies have proposed a role for the hippocampus in the rapid encoding of context memories. Despite this, there is little data regarding the molecular processes underlying the stable formation of a context representation that occurs in the time window established through such behavioral studies. One task that is useful for investigating the rapid encoding of context is contextual fear conditioning (CFC). Behavioral studies demonstrate that animals require approximately 30 s of exploration prior to a footshock to form a contextual representation supporting CFC. Thus, any potential molecular process required for the stabilization of the cellular representation for context must be activated within this narrow and behaviorally defined time window. Detection of the immediate-early gene Arc presents an ideal method to assess the activation of specific neuronal ensembles, given past studies showing the context specific expression of Arc in CA3 and CA1 subfields and the role of Arc in hippocampal long-term synaptic plasticity. Therefore, we examined the temporal dynamics of Arc induction within the hippocampus after brief context exposure to determine whether experience-dependent Arc expression could be involved in the rapid encoding of incidental context memories. We found that the duration of context exposure differentially activated Arc expression in hippocampal subfields, with CA3 showing rapid engagement within as little as 3 s of exposure. By contrast, Arc induction in CA1 required 30 s of context exposure to reach maximal levels. A parallel behavioral experiment revealed that 30 s, but not 3 s, exposure to a context resulted in strong conditioned freezing 24 h later, consistent with past studies from other laboratories. The current study is the first to examine the rapid temporal dynamics of Arc induction in hippocampus in a well-defined context memory paradigm. These studies demonstrate within 30 s of context exposure Arc is fully activated in CA3 and CA1, suggesting that the engagement of plastic processes requiring Arc function (such as long-term potentiation) occurs within the same temporal domain as that required for behavioral conditioning.
过去的研究提出了海马体在快速编码上下文记忆中的作用。尽管如此，关于在这种行为研究建立的时间窗口内稳定形成上下文表示的分子过程，数据很少。一个用于研究上下文快速编码的有用任务是情境恐惧条件反射（CFC）。行为研究表明，动物需要大约 30 秒的探索才能形成支持 CFC 的情境表示。因此，对于稳定情境细胞表示所需的任何潜在分子过程，必须在这个狭窄的和行为定义的时间窗口内激活。检测即时早期基因 Arc 提供了一种评估特定神经元集合激活的理想方法，因为过去的研究表明 Arc 在 CA3 和 CA1 子场中的上下文特异性表达，以及 Arc 在海马体长期突触可塑性中的作用。因此，我们检查了短暂暴露于上下文后海马体中 Arc 诱导的时间动态，以确定经验依赖性 Arc 表达是否参与了偶然上下文记忆的快速编码。我们发现，暴露于短时间的环境刺激会导致海马体亚区的 Arc 表达产生不同的激活，CA3 在暴露后仅 3 秒内就迅速参与。相比之下，CA1 中的 Arc 诱导需要 30 秒的上下文暴露才能达到最大水平。一项平行的行为实验表明，30 秒而不是 3 秒的暴露于情境会导致 24 小时后强烈的条件性冻结，与其他实验室的过去研究一致。本研究首次在一个明确的情景记忆范式中检查了海马体中 Arc 诱导的快速时间动态。这些研究表明，在暴露于情境后的 30 秒内，Arc 在 CA3 和 CA1 中完全被激活，这表明需要 Arc 功能的可塑性过程（如长时程增强）的参与发生在与行为调节相同的时间范围内。
