Emergence of memory engrams in the rodent hippocampus

海马体对有意识记忆的储存起决定性作用。记忆特异性神经元群——也就是所谓的“印痕”——存在于啮齿类动物海马体的所有子区域。然而，在长期学习过程中，这些记忆印迹是如何发展和维持特定记忆活动的，这方面的知识很少。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在虚拟现实中执行目标导向空间记忆任务的头部固定小鼠海马中的群体活动，并记录主要海马亚区，齿状回，CA1和CA3的主要细胞活动。海马主细胞亚群具有位置细胞特征，并在小鼠探索特定空间场时放电。然而，目前尚不清楚的是，在学习过程中，代表空间环境的位置细胞集合如何在海马体的三个子区中出现。为了解决这个问题，我们最近建立了一种行为模式，在这种模式中，头部固定的老鼠探索一个“熟悉的”虚拟环境，在这个环境中，它们经过几天的训练，在特定的位置获得食物奖励。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，我们将首先研究在随后几天的“新”环境中的学习过程中，位置细胞组合是如何出现的，以及它们与代表熟悉环境的细胞关联有何不同。其次，我们的目的是测试三个海马区对学习到的新空间环境的表征的可靠性以及两种环境之间的区分是否不同。最后，我们的目标是研究来自内侧内嗅皮层传递上下文信息的输入对代表空间环境的海马细胞集合特征的影响。因此，在这个提议的项目中，我们的目标是更好地理解基于齿状回提供的代码的经典海马三突触环路的记忆表征。

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.