Imaging excitatory synaptic input to hippocampal dendritic segments during spatial navigation

空间导航过程中海马树突段的兴奋性突触输入成像

• 批准号: 10396808
• 负责人: Heydar Davoudi
• 金额: $ 3.52万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396808
• 关键词: Alzheimer' s Disease; Apical; Area; Automobile Driving; Cells; Cognitive; Color; Dendrites; Dendritic Spines; Distal; Environment; Episodic memory; Fire - disasters; Functional Imaging; Future; Glutamates; Head; Hippocampus (Brain); Image; Learning; Location; Maps; Measures; Memory; Mental disorders; Mus; Neurobiology; Neurons; Output; Pathway interactions; Pattern; Perforant Pathway; Play; Property; Rodent; Role; Schizophrenia; Signal Transduction; Sum; Synapses; Testing; Universities; base; calcium indicator; cell cortex; entorhinal cortex; imaging approach; in vivo imaging; nervous system disorder; neuronal cell body; novel; place fields; preservation; spatial memory; two photon microscopy; two-photon; virtual; virtual environment; virtual reality; virtual reality environment; way finding

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.

空间导航过程中海马树突段的兴奋性突触输入成像 Heydar Davoudi，西北大学神经生物学系 项目概要/摘要 海马体在空间导航和情景记忆的形成中起着至关重要的作用。海马 输出区 CA1 对于空间学习和记忆至关重要，它接收来自以下方面的主要兴奋性输入： 内嗅皮层 (EC) 通过穿孔通路 (PP) 并从海马区 CA2 和 CA3 通过 Schaffer 侧支 (SC) 通路。在探索过程中，啮齿动物的 CA1 神经元表现出特定位置的活动 称为这些“位置细胞”的位置场。 CA1 位置场可能由 PP 和 SC 输入路径驱动 到达 CA1 树突棘。然而，尚不清楚这两种途径发挥什么不同的作用。 驱动空间学习和记忆所需的 CA1 位置细胞活动。在此，我建议开发一个 以前无法实现的 CA1 位置细胞体同时双色双光子功能成像 它在头部固定的小鼠在虚拟现实环境中导航时产生突触规模的兴奋性输入。我的目标是 开发基于微棱镜和基于贝塞尔光束的双光子显微镜对 CA1 位置细胞体进行成像 对其基底和远端簇树突段的突触规模兴奋性输入，分别接收 来自 SC 和 PP 途径的输入。这使我能够确定不同的兴奋性突触输入如何 这两条路径所携带的对熟悉轨道中的体细胞位置场的不同贡献 学习新的虚拟环境。总而言之，该提案旨在增加我们对突触的理解 认知处理水平在阿尔茨海默病等神经和精神疾病中受到干扰 疾病和精神分裂症。