Emergence of memory engrams in the rodent hippocampus

海马体对于有意识记忆的储存起着决定性的作用。记忆特异性神经元集合--所谓的记忆痕迹--存在于啮齿动物海马体的所有子区域。然而，关于这些记忆痕迹如何在长期学习中发展和维持记忆特异性活动的知识很少。在这里提出的项目中，我们的目标是使用慢性双光子钙成像的群体活动在海马的头部固定小鼠执行目标为导向的空间记忆任务在虚拟现实和记录主要的海马子领域，齿状回，CA 1和CA 3的主要细胞活动。海马主细胞的亚群具有定位细胞的特征，一旦小鼠探索特定的空间场，就会放电。然而，它仍然是不清楚的地方细胞组件作为一个整体，代表空间的背景下出现在学习过程中的三个海马子领域。为了解决这个问题，我们最近建立了一个行为范式，在这个范式中，头部固定的小鼠探索一个“熟悉的”虚拟环境，在这个环境中，它们已经接受了几天的训练，以在特定位置获得食物奖励。在熟悉的环境中训练后，老鼠被暴露在一个“新的”虚拟环境中，以探索新的奖励地点。在拟议的项目中，我们将首先，研究如何在学习过程中出现的“新”的背景下，在随后的日子里，他们如何不同于代表熟悉的背景下的细胞协会的地方细胞组件。第二，我们的目标是测试是否可靠性的代表性的学习新的空间环境，以及这两种情况之间的区别不同的三个海马区。最后，我们的目的是研究从内侧内嗅皮层传输上下文信息的输入的影响，海马细胞组件代表的空间环境的特点。因此，在这个拟议的项目中，我们的目标是获得一个更好的理解，在代表性的记忆沿着经典的海马三突触环的基础上提供的代码的齿状回。

The hippocampus is decisive for the storage of conscious memories. Memory-specific neuronal ensembles – so called engrams – exist in all subfields of the rodent hippocampus. However, knowledge about how these engrams develop and maintain memory-specific activity during long-term learning is scarce. In the here proposed project, we aim to use chronic two-photon calcium imaging of population activity in the hippocampus of head-fixed mice performing a goal-oriented spatial memory tasks in a virtual reality and record principal cell activity in the major hippocampal subfields, the dentate gyrus, CA1 and CA3. A subpopulation of hippocampal principal cells have place cell characteristics and discharge once the mouse explores a specific spatial field. It remains, however, unclear how place cell assemblies as a whole representing spatial contexts emerge in the three hippocampal subfields during learning. To address this question we recently established a behavioural paradigm in which head-fixed mice explore a ‘familiar’ virtual environment in which they have been trained over several days to obtain food rewards at specific locations. After training in the familiar context, mice are exposed to a ‘novel’ virtual environment to explore new reward locations. In the proposed project, we will first, examine how place cell assemblies emerge during the learning process in the ‘novel’ context on subsequent days and how they differ from cell associations representing the familiar context. Second, we aim to test whether reliability in the representation of the learned novel spatial environment as well as the differentiation between both contexts differs among the three hippocampal areas. Finally, we aim to examine the influence of inputs from the medial entorhinal cortex transmitting contextual information, on the characteristics of hippocampal cell assemblies representing a spatial environment. Thus, within this proposed project we aim to obtain a better understanding in the representation of memories along the classic hippocampal tri-synaptic loop based on the code provided by the dentate gyrus.