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.

项目概述：记忆使动物能够通过以下方式获得、储存和回忆世界知识： 经验和使用这些知识，以最大限度地提高回报和避免危险。了解电路 大脑区域内部和之间的机制，形成和回忆的记忆被认为是 这是我们这个时代最大的科学挑战之一，有可能极大地影响治疗。 记忆障碍海马体对于情景记忆的形成和回忆是必要的，也是充分的。 记忆--对时间和空间中经历的记忆。这些记忆被编码在 海马体是通过被称为位置细胞的神经元群体的放电活动来实现的，这些神经元在特定的位置放电 当动物在它们的环境中移动时，创造了一个认知地图。了解认知地图是如何形成的， 随着经验而进化，因此，对于理解记忆的神经生物学至关重要。 以及海马体在这个过程中的作用。然而，一个主要的途径， 在记忆和海马体的研究中被忽视的是CA 3之间的跨半球投射。 和海马体的CA 1区。这种投射为CA 1区域提供了主要的兴奋性驱动， 这些投射传递给CA 1的信息是未知的，它们对CA 1记忆编码的影响也是未知的。 由于技术限制，无法直接记录和比较半球内与半球间的差异。 半球CA 3在记忆处理期间输入到CA 1。 为了解决这个问题，我们将采用一种创新的方法，直接测量和操纵 在CA 1中，半球内与跨半球CA 3轴突的尖峰活动。同时，我们也将 在空间学习过程中记录大量CA 1位置细胞的尖峰活动-新环境 exposure.活动的功能成像加上海马CA 3轴突的光遗传学操纵将 揭示了半球内和跨半球CA 3输入对认知地图的贡献 形成、进化和恢复。这将提供第一个洞察所携带的信息， 在空间学习过程中，大脑半球内与跨半球的CA 3轴突直接位于CA 1，并将揭示 这些输入如何影响CA 1的记忆表征。这些见解可以揭示新的目标， 治疗记忆障碍的方法。