Synaptic Mechanisms for Contextual Memory Formation

学习和记忆决定了动物如何与环境互动。这个过程取决于 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。 虽然突触可塑性对学习和记忆至关重要，但记忆的机制 形成并储存在神经回路中的机制仍然知之甚少。拟议的研究涉及 通过关注编码上下文记忆的突触机制， 海马CA 3锥体神经元中，海马是一个在学习和 记忆在会聚到CA 3锥体神经元的兴奋性输入中，苔藓纤维 (MF)已知来自齿状回颗粒细胞的输入对于上下文信息的编码是必需的。 记忆利用我们最近开发的遗传工具，我们能够识别出特定的群体， 的CA 3神经元激活的上下文学习，并确定了学习依赖性突触 与这些神经元相关的变化。我们假设这个新发现的突触 可塑性在情境记忆的形成中起着关键作用。该假设将通过以下方式进行检验： 在小鼠中结合分子、细胞、电生理和行为方法。我们 还将确定选择性调节小鼠MF-CA 3突触的分子通路 海马体。拟议中的研究有可能在以下方面产生概念性突破： 我们对记忆形成的分子和细胞理解， 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.