Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation

空间导航过程中兴奋性突触传入海马树突段的成像 西北大学神经生物学系Heydar Davoudi 项目摘要/摘要 海马体在空间导航和情景记忆的形成中起着关键作用。海马区 输出区CA1是空间学习和记忆的关键区域，它接受来自 内嗅皮层(EC)经穿支通路(PP)和从海马区CA2和CA3至 Schaffer侧支(SC)通路。在探索过程中，啮齿类动物的CA1神经元显示出特定位置的活动 称为这些“位置单元格”的位置字段。CA1位场可以由PP和SC输入路径驱动 到达CA1树突棘。然而，目前尚不清楚这两条途径在其中起到了什么不同的作用 驱动CA1区的细胞活动是空间学习和记忆所必需的。在这里，我建议开发一种 以前无法获得的CA1场所细胞胞体的同时双色双光子功能成像和 它的突触规模的兴奋性输入在头部固定的老鼠在虚拟现实环境中导航。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来成像CA1场所细胞胞体和 突触尺度兴奋性传入其基底节和远侧丛树突节段，分别接受 来自SC和PP通路的输入。这让我能够确定不同的兴奋性突触输入是如何 由这两条路径携带的身体部位场在熟悉的轨迹上和在 学习新的虚拟环境。总之，这项建议旨在增加我们对突触- 阿尔茨海默氏症等神经性和精神性疾病的认知水平被破坏 疾病和精神分裂症。

Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation Heydar Davoudi, Department of Neurobiology, Northwestern University Project Summary/Abstract 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.