Synaptic Mechanisms for Contextual Memory Formation

学习和记忆定义了动物如何与环境互动。这一过程依赖于 经验驱动的突触连接变化，这种现象被称为突触可塑性； 这一过程的中断被认为是几种认知和精神障碍的基础。 尽管突触可塑性对学习和记忆至关重要，但记忆 形成并储存在神经回路中，目前仍知之甚少。拟议的研究旨在解决 通过关注语境记忆编码的突触机制，这种知识鸿沟 在海马区的CA3锥体神经元中，一个在学习和学习中起中心作用的脑区 记忆。在汇聚到CA3锥体神经元的兴奋性输入中，苔藓纤维 已知来自齿状回颗粒细胞的(MF)输入是语境编码所必需的 记忆。使用我们最近开发的基因工具，我们能够识别出特定的群体 由情景学习激活的CA3神经元，并确定了一个学习依赖的突触 与这些神经元相关的修饰。我们假设这个新发现的突触 可塑性在语境记忆的形成中起着至关重要的作用。这一假设将通过以下方式进行检验 小鼠的分子、细胞、电生理和行为方法的结合。我们 还将识别选择性地调节小鼠MF-CA3突触的分子途径 海马体。拟议的研究有可能在以下方面产生概念上的突破 我们对记忆形成的分子和细胞的理解，并最终提供洞察力 认知和精神障碍的潜在机制。

Learning and memory defines how animals interact with their environment. This process relies on experience-driven changes in synaptic connections, a phenomenon known as synaptic plasticity; disruption of this process is believed to underlie several cognitive and psychiatric disorders. Although synaptic plasticity is critical for learning and memory, the mechanisms by which memory is formed and stored in neural circuits remains poorly understood. The proposed studies address this knowledge gap by focusing on synaptic mechanisms by which contextual memory is encoded in CA3 pyramidal neurons of the hippocampus, a brain region with a central role in learning and memory. Among the excitatory inputs converging onto CA3 pyramidal neurons, the mossy fiber (MF) input from dentate gyrus granule cells is known to be required for the encoding of contextual memory. Using genetic tools recently developed by us, we were able to identify the specific group of CA3 neurons activated by contextual learning, and identified a learning-dependent synaptic modifications associated with these neurons. We hypothesize that this newly identified synaptic plasticity plays a critical role in contextual memory formation. This hypothesis will be tested using a combination of molecular, cellular, electrophysiological and behavioral approaches in mice. We will also identify molecular pathways that selectively modulate MF-CA3 synapses in the mouse hippocampus. The proposed research has the potential to generate conceptual breakthroughs in our molecular and cellular understanding of memory formation, and ultimately provide insights into mechanisms underlying cognitive and psychiatric impairments.