The mossy fiber synapse - imprinting a memory trace in CA3

对生活事件的记忆是我们思考和个性的基本基础。记忆能力的丧失或改变经常出现在痴呆症或抑郁症中，对受影响的人来说是毁灭性的。然而，人们对情景记忆的存储和提取机制知之甚少。海马体是这一过程中必不可少的大脑区域。根据目前的理论，海马区CA3区的高度互联网络存储了由投射到海马区的皮质神经元编码的记忆的各个元素之间的联系。此外，CA3接受来自齿状回颗粒细胞的突触输入，齿状回是另一个海马区。这些输入对于存储记忆是至关重要的，但对于记忆回忆来说往往是必不可少的。然而，记忆存储所需的CA3区突触连接和活动模式的变化以及颗粒细胞在这一过程中的作用仍然是个谜。因此，该项目的目的是从执行空间记忆任务的小鼠的齿状回和CA3神经元获得同时的高密度电生理记录。我们将观察它们与记忆相关的放电活动，并检测突触连接的颗粒细胞对及其突触后靶细胞，以确定颗粒细胞活动对记忆编码、巩固和提取的影响。此外，我们将使用光遗传操作来确定颗粒细胞活动对与记忆相关的神经网络功能和行为的作用。拟议的实验将在我们对记忆机制的理解方面取得实质性进展，这是未来开发潜在的记忆障碍治疗方法不可或缺的先决条件。

Memories about the events of our lives are a fundamental basis for our thinking and personality. Loss or alterations in the ability to remember such episodes, frequently observed in dementia or depression, are devastating for those affected. Nevertheless, the mechanisms of storage and retrieval of episodic memories are poorly understood. The hippocampus is a brain area essential for this process. According to current theories, the highly interconnected network of the hippocampal CA3 subfield stores associations between individual elements of memories encoded by cortical neurons projecting to the hippocampus. Furthermore, CA3 receives synaptic inputs from granule cells in the dentate gyrus, another hippocampal area. These inputs are critical for storing memories, but often dispensable for memory recall. However, the changes in synaptic connectivity and activity patterns in CA3 required for memory storage and the role of granule cells in that process remain enigmatic. The aim of the proposed project is thus to acquire simultaneous high-density electrophysiological recordings from dentate gyrus and CA3 neurons in mice performing a spatial memory task. We will observe their memory-related firing activity and detect synaptically connected pairs of granule cells and their postsynaptic targets to determine the impact of granule cell activity on memory encoding, consolidation and retrieval. Furthermore, we will use optogenetic manipulations to identify the role of granule cell activity on memory-related neuronal network functions and behavior. The proposed experiments will yield substantial advances in our understanding of memory-mechanisms, which are indispensable prerequisites for the future development of potential therapies for memory disorders.