Encoding properties of bilateral CA3 inputs and their contribution to the formation and dynamics of CA1 spatial representations in novel environments

双边 CA3 输入的编码特性及其对新环境中 CA1 空间表示的形成和动态的贡献

• 批准号: 10510787
• 负责人: Mark E J Sheffield
• 金额: $ 43.62万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10510787
• 关键词: Acceleration; Alzheimer' s Disease; Anatomy; Animals; Axon; Bilateral; Brain Diseases; Brain region; Calcium; Cells; Cellular Structures; Cognitive; Communication; Contralateral; Dendritic Spines; Development; Environment; Episodic memory; Evolution; Exposure to; Fire - disasters; Functional Imaging; Goals; Head; Hippocampus (Brain); Image; Ipsilateral; Knowledge; Learning; Left; Linear Models; Location; Long-Term Potentiation; Maps; Measures; Memory; Memory Disorders; Memory impairment; Modeling; Morphology; Mus; Neurobiology; Neurons; Neurosciences; Output; Paper; Pathway interactions; Patients; Population; Population Dynamics; Problem Solving; Process; Property; Publishing; Pyramidal Cells; Resolution; Retrieval; Rewards; Role; Schizophrenia; Stream; Synapses; Testing; Time; Work; dentate gyrus; experience; experimental study; innovation; insight; memory encoding; memory process; memory recall; memory retrieval; neglect; neural circuit; novel; optogenetics; place fields; prevent; spatial memory; two-photon; virtual environment

Project Summary: Memory enables animals to acquire, store, and recall knowledge of the world through experience and use this knowledge to maximize reward and avoid danger. Understanding the circuit mechanisms within and between brain regions that underlie the formation and recall of memories is considered one of the great scientific challenges of our time and has the potential to drastically influence the treatment of memory disorders. The hippocampus is both necessary and sufficient for the formation and recall of episodic memories—memories of experiences placed in time and space. These memories are encoded in the hippocampus by the firing activity of populations of neurons called place cells, which fire at specific locations as animals move around their environment, creating a cognitive map. Understanding how cognitive maps form, evolve with experience, and are retrieved is therefore essential for understanding the neurobiology of memory and the function of the hippocampus in this process. However, a major pathway that has been overwhelmingly neglected in the study of memory and the hippocampus is the across hemispheres projection between the CA3 and CA1 region of the hippocampus. This projection provides major excitatory drive to the CA1 region, yet the information these projections convey to CA1 is unknown, as is their impact on CA1 memory encoding. Technical limitations have prevented direct recordings and comparisons of within-hemisphere versus across- hemisphere CA3 inputs to CA1 during memory processing. To solve this problem, we will implement an innovative approach to directly measure and manipulate the spiking activity of within-hemisphere versus across-hemisphere CA3 axons in CA1. We will also simultaneously record the spiking activity of large populations of CA1 place cells during spatial learning — novel environment exposure. Functional imaging of activity plus optogenetic manipulation of CA3 axons in hippocampus will reveal the contribution of within-hemisphere versus across-hemisphere CA3 inputs on cognitive map formation, evolution and retrieval. This will provide the first insight into the information being carried by within-hemisphere versus across-hemisphere CA3 axons directly in CA1 during spatial learning and will reveal how these inputs contribute to memory representations in CA1. These insights could reveal novel targets or processes for the treatment of memory disorders.

项目摘要：记忆使动物能够通过 体验和利用这些知识来最大化奖励并避免危险。了解电路 考虑记忆形成和回忆的大脑区域内和大脑区域之间的机制被视为 我们这个时代的科学挑战之一，有可能极大地影响 记忆障碍。海马既需要且足以形成和回忆 回忆 - 时空的经验记忆。这些记忆是在 海马通过称为位置细胞的神经元种群的发射活性，在特定位置发射 随着动物在环境中移动，创建认知图。了解认知图的形成方式， 因此，具有经验的进化，因此被检索对于理解记忆的神经生物学至关重要 以及海马在此过程中的功能。但是，这是一条绝大多数的主要途径 在记忆和海马研究中被忽略的是CA3之间的跨半球投影 海马的CA1区域。该预测为CA1区域提供了主要的兴奋驱动器 这些项目传达给CA1的信息尚不清楚，它们对CA1记忆编码的影响也是如此。 技术限制阻止了直接记录和半球内与跨性别的比较 在记忆处理过程中，半球CA3输入到CA1。 为了解决这个问题，我们将采用一种创新的方法来直接衡量和操纵 CA1中半球内与半球CA3轴突的尖峰活性。我们也将 在空间学习过程中记录大量CA1的峰值活性 - 新的环境 接触。活动的功能成像以及海马中CA3轴突的光遗传操作将 揭示了半球内与半球CA3在认知图上的贡献 形成，进化和检索。这将为您携带的信息提供第一个见解 在空间学习过程中，在CA1中直接在半球内与跨半球CA3轴突，并将揭示 这些输入如何促进CA1中的内存表示。这些见解可以揭示新的目标或 治疗记忆障碍的过程。