Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation.

海马体在空间导航和情景记忆的形成中起着关键作用。海马输出区CA1对空间学习和记忆至关重要，它通过穿孔通路（PP）接收来自内嗅皮层（EC）的主要兴奋性输入，并通过谢弗侧枝通路（SC）接收来自海马区CA2和CA3的主要兴奋性输入。在探索过程中，啮齿动物的CA1神经元显示出被称为“位置细胞”的位置场的位置特异性活动。CA1位置场可能由到达CA1树突棘的PP和SC输入通路驱动。然而，这两种途径在驱动空间学习和记忆所必需的CA1位置细胞活动中发挥的不同作用尚不清楚。在这里，我建议开发一种以前无法实现的同时双色双光子功能成像，用于在虚拟现实环境中导航的头部固定小鼠的CA1位置细胞体及其突触尺度的兴奋性输入。我的目标是开发基于微棱镜和贝塞尔光束的双光子显微镜，以成像CA1位置细胞体细胞及其基底和远端丛状树突段的突触尺度兴奋输入，它们分别接受SC和PP通路的输入。这使我能够确定这两条通路携带的不同兴奋性突触输入如何在熟悉的轨道和学习新的虚拟环境中不同地促进躯体位置场。总之，这一建议旨在增加我们对神经和精神疾病（如阿尔茨海默病和精神分裂症）中被破坏的突触水平认知加工的理解。

The hippocampus has a critical role in spatial navigation and formation of episodic memories. Hippocampal output area CA1 is crucial for spatial learning and memory and it receives major excitatory inputs from entorhinal cortex (EC) through the Perforant pathway (PP) and from hippocampal areas CA2 and CA3 through the Schaffer collateral (SC) pathways. During exploration, a rodent’s CA1 neurons show location-specific activity known as place fields of these “place cells”. CA1 place fields may be driven by PP and SC input pathways arriving on CA1 dendritic spines. However, it is unknown what different roles these two pathways play in driving the CA1 place cell activity necessary for spatial learning and memory. Here, I propose to develop a previously unattainable simultaneous dual-color two-photon functional imaging of a CA1 place cell soma and its synaptic-scale excitatory input in head-fixed mice navigating through a virtual-reality environment. I aim to develop microprism-based and Bessel beam-based two-photon microscopies to image a CA1 place cell soma and the synaptic-scale excitatory input to its basal and distal tuft dendritic segments, which respectively receive inputs from SC and PP pathways. This allows me to determine how the different excitatory synaptic inputs carried by these two pathways differentially contribute to somatic place fields in a familiar track and during learning a new virtual environment. Altogether, this proposal aims to add to our understanding of synaptic- level cognitive processing which is disrupted in neurological and psychiatric diseases such as Alzheimer’s disease and schizophrenia.