Biphasic expression of plasticity genes in the stabilization of hippocampal and neocortical fear memory neuronal ensembles.

虽然持久性是某些记忆的一个关键特征，但决定记忆是暂时存储还是永久存储的因素还不清楚。一些研究和我们自己的初步工作表明，持久记忆的巩固与学习后海马和新皮层区域可塑性相关基因表达的重新激活有关。重要的是，转录再激活是不存在的经验后，只存储了很短的一段时间。因此，我们假设，转录激活提供了一个分子和细胞的强化机制，为稳定的神经元合奏持久的形式的记忆。我们将在一个恐惧记忆的范例中解决这个假设。首先，我们将确定后期转录反应是否选择性地发生在学习时形成的神经元系综内，以及它是否是记忆表征长期稳定所必需的。这将通过组合标记工具和免疫组织学分析来实现。第二，我们将识别触发不同持续时间记忆的学习经历的细胞相关性。我们将描述与短期和长期记忆相关的标记神经元系综的功能和结构特征。 我们的初步研究结果表明，学习刺激诱导短期或长期形式的记忆触发不同的可塑性相关基因的表达模式。因此，我们将测试这些可塑性相关基因的表达是否决定了与短期或长期记忆相关的神经元集合的不同特性。最后，我们将研究老年动物记忆持续性受损是否是神经元系综稳定性破坏的结果。我们推测，可塑性相关基因的转录再激活在老年小鼠的海马和新皮层减少。总之，我们的实验将有助于揭示转录再激活是否以及如何决定与持久记忆相关的海马和新皮层合奏的稳定性。

Although persistence is a key characteristic of some memories, what determines whether a memory will be transiently or permanently-stored is not understood. A few studies and our own preliminary work show that consolidation of persistent memories is associated with the reactivation of expression of plasticity-related genes at later time points after learning in both hippocampal and neocortical regions. Importantly, transcriptional reactivation is absent after experiences which are only stored for short periods of time. We therefore hypothesize that transcriptional reactivation provides a molecular and cellular reinforcement mechanism necessary for the stabilization of neuronal ensembles underlying long-lasting forms of memory. We will address this hypothesis in a fear-memory paradigm. First, we will determine whether the late transcriptional response occurs selectively within the neuronal ensemble formed at the time of learning, and whether it is necessary for long-term stabilization of memory representations. This will be achieved by combining ensemble-tagging tools and immunohistological analysis. Second, we will identify the cellular correlates of learning experiences triggering memories of different duration. We will characterize functional and structural features of the -tagged- neuronal ensemble(s) associated with short-lasting and long-lasting memory. Our preliminary findings show that learning stimuli inducing short or long forms of memory trigger distinct expression patterns of plasticity-related genes. Therefore, we will test whether expression of these plasticity-related genes determines the different properties of neuronal ensembles associated with short or long-lasting memory. Finally, we will investigate whether impaired memory persistence in aged animals is a result of disrupted stabilization of neuronal ensembles. We hypothesize that transcriptional reactivation of plasticity-related genes is reduced in the hippocampus and neocortex of aged mice. Together, our experiments will help revealing whether and how transcriptional reactivation determines the stability of hippocampal and neocortical ensembles associated with long-lasting memory.