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

项目摘要：记忆使动物能够通过记忆获取、存储和回忆世界的知识 体验并使用这些知识来最大限度地获得回报和避免危险。了解电路 大脑区域内和大脑区域之间形成和回忆记忆的机制被考虑在内。 这是我们时代最大的科学挑战之一，有可能极大地影响对 记忆障碍。海马体对于情节的形成和回忆是必要和充分的。 记忆--对放置在时间和空间中的经历的记忆。这些记忆被编码在 通过称为位置细胞的神经元群体的放电活动来激活海马体，这些神经元在特定的位置放电 当动物在他们的环境中移动时，就会产生一张认知地图。了解认知地图是如何形成的， 因此，随着经验而进化，并被重新获得，对于理解记忆的神经生物学是必不可少的 以及海马体在这一过程中的功能。然而，一条压倒性的主要途径 在记忆和海马体的研究中被忽视的是CA3之间的跨半球投射 和海马区CA1区。这一投射为CA1区提供了主要的兴奋性驱动，但 这些投影传递给CA1的信息是未知的，它们对CA1记忆编码的影响也是未知的。 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的方法来直接测量和操作 CA1的半球内轴突与跨半球CA3轴突的放电活动。我们还将同时 记录大群CA1区细胞在空间学习过程中的放电活动--新环境 曝光。脑海马CA3轴突活动和光遗传操作的功能成像 揭示半球内CA3输入与跨半球CA3输入对认知图谱的贡献 形成、进化和检索。这将提供第一次深入了解由 在空间学习期间直接在CA1内的半球内和跨半球的CA3轴突，并将揭示 这些输入如何对CA1中的记忆表示做出贡献。这些洞察力可能揭示新的目标或 记忆障碍的治疗过程。

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.