Dynamics of Information Flow in the Hippocampal Circuit

描述(申请人提供)：海马体和内侧颞叶的相邻结构对于快速编码关于事实、地点和事件的新记忆的能力是必不可少的。当探索新的环境时，海马体必须协调传入的感觉体验和存储的表征，以形成新的记忆。我的长期研究目标是了解正在进行的行为如何塑造电路功能，以及这种能力在病理状态下可能会如何改变。在这个研究方案中，我重点研究行为状态和新颖性如何塑造海马体中的电路功能。具体地说，这项建议侧重于作为海马体主要输出的CA1亚区及其输入，即内嗅皮层(EC)的第三层和海马亚区CA3。这些输入被认为是向CA1传达关于当前感觉体验(EC)和内部存储的表征(CA3)的信息。虽然这些区域已经成为许多研究的对象，但几乎没有人知道CA1在学习过程中如何动态地耦合和整合来自CA3和EC的输入。在这里，我建议使用多电极植入来记录大鼠CA1、CA3和EC中同时的神经活动，因为动物探索一个最初新的环境，了解一个最初新的任务。我的具体目标是：具体目标1：检验在学习过程中，行为状态持续调节通过海马体回路的信息流的假设。具体目标2：检验学习增强海马区表征的时间对齐这一假设。实现这些特定的目标将揭示行为和学习如何主动塑造海马体-内嗅觉回路中的回路功能，更广泛地说，这项工作将有助于我们理解经验是如何塑造大脑中的信息处理的。这项研究是了解这些动力学如何在涉及海马体结构的各种神经疾病中出错的先决条件。 与公共健康相关：海马体是大脑的一部分，对我们日常记忆新事实、新地点和新事件的能力非常重要。海马体功能障碍与年龄相关的记忆丧失、自闭症谱系障碍、精神分裂症、抑郁症和成瘾有关，但我们不知道海马体功能异常如何导致在这些疾病中观察到的复杂行为变化。这项拟议的研究将帮助我们更好地了解海马体回路的正常功能，从而更好地理解并最终治疗这些疾病。

DESCRIPTION (provided by applicant): The hippocampus and adjacent structures in the medial temporal lobe are essential for the ability to rapidly encode new memories for facts, places and events. When exploring a novel environment, the hippocampus must reconcile incoming sensory experience with stored representations to form a new memory. My long- term research goals are to understand how ongoing behavior shapes circuit function and how this ability may be altered in pathological states. In this research proposal, I focus on how behavioral state and novelty shape circuit function in the hippocampus. Specifically, this proposal focuses on subfield CA1, which serves as the main output of the hippocampus, and its inputs, layer III of the entorhinal cortex (EC) and hippocampal subfield CA3. These inputs are thought to convey information to CA1 about current sensory experience (EC) and internally stored representations (CA3). While these regions have been the subjects of many investigations, almost nothing is known about how CA1 dynamically couples with and integrates input from CA3 and EC during learning. Here, I propose to use multi-electrode implants to record simultaneous neural activity in CA1, CA3, and the EC of rats as animals explore an initially novel environment and learn about an initially novel task. My specific aims are: Specific Aim 1: To test the hypothesis that during learning, behavioral state continuously modulates information flow through the hippocampal circuit. Specific Aim 2: To test the hypothesis that learning enhances the temporal alignment of representations across the hippocampal circuit. Accomplishing these specific aims will reveal how behavior and learning actively shape circuit function in the hippocampal-entorhinal circuit and more broadly, this work will contribute to our understanding of how experience shapes information processing in the brain. This research is a prerequisite to understanding how these dynamics go awry in various neurological disorders that involve the hippocampal formation. PUBLIC HEALTH RELEVANCE: The hippocampus is a part of the brain that is important for our everyday ability to remember new facts, places and events. Dysfunction of the hippocampus is associated with age-related memory loss, autism spectrum disorders, schizophrenia, depression, and addiction, but we do not understand how aberrations in hippocampal function contributes to the complex behavioral changes observed in these diseases. The proposed research will help us better understand the normal functioning of the hippocampal circuit, leading to better understanding of and ultimately treatments for these disorders.