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

尽管持久性是某些记忆的一个关键特征，但决定记忆是短暂存储还是永久存储的因素尚不清楚。一些研究和我们自己的初步工作表明，持久记忆的巩固与海马和新皮质区域在学习后较晚时间点的可塑性相关基因表达的再激活有关。重要的是，转录再激活在只存储短时间的经历之后是不存在的。因此，我们假设转录再激活提供了一种分子和细胞强化机制，这对于稳定长期记忆形式下的神经元集合是必要的。我们将在恐惧-记忆范式中解决这个假设。首先，我们将确定晚转录反应是否选择性地发生在学习时形成的神经元集合中，以及它是否对记忆表征的长期稳定是必要的。这将通过组合集成标记工具和免疫组织学分析来实现。其次，我们将确定触发不同持续时间记忆的学习经验的细胞相关性。我们将描述与短时记忆和长时记忆相关的标记神经元集合的功能和结构特征。我们的初步研究结果表明，学习刺激引起的短期或长期记忆会触发与可塑性相关的基因的不同表达模式。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的记忆持久性受损是否是神经元群稳定被破坏的结果。我们假设，在老年小鼠的海马体和新皮层中，可塑性相关基因的转录再激活减少。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体和新皮层整体的稳定性。

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.