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以下方式获取、存储和回忆世界知识： 经验并利用这些知识来最大化奖励并避免危险。 考虑了记忆形成和回忆的大脑区域内部和之间的机制 我们这个时代最大的科学挑战之一，有可能对治疗产生巨大影响 海马体对于情景的形成和回忆既是必要的也是充分的。 记忆——放置在时间和空间中的经历的记忆这些记忆被编码在 海马体由称为位置细胞的神经元群的放电活动控制，这些神经元在特定位置放电 当动物在其环境中移动时，创建认知地图，了解认知地图是如何形成的。 随着经验的发展，并被检索，因此对于理解记忆的神经生物学至关重要 然而，海马体在这一过程中的功能却是压倒性的。 在记忆和海马体的研究中被忽视的是 CA3 之间的跨半球投影 该投影为 CA1 区域提供了主要的兴奋驱动力。 这些投影向 CA1 传达的信息以及它们对 CA1 记忆编码的影响都是未知的。 技术限制阻碍了半球内与跨半球的直接记录和比较 在记忆处理过程中，半球 CA3 输入到 CA1。 为了解决这个问题，我们将实施一种创新方法来直接测量和操纵 我们还将同时比较 CA1 中半球内与跨半球 CA3 轴突的尖峰活动。 记录空间学习期间大量 CA1 位置细胞的尖峰活动——新环境 海马 CA3 轴突的活动功能成像和光遗传学操作将被暴露。 揭示半球内与跨半球 CA3 输入对认知图的贡献 这将提供对所携带信息的第一视角。 半球内与跨半球 CA3 轴突直接位于 CA1 空间学习期间，并将揭示 这些输入如何有助于 CA1 中的记忆表征。这些见解可以揭示新的或新的目标。 治疗记忆障碍的过程。