Dynamics of Information Flow in the Hippocampal Circuit

描述（由申请人提供）：海马体和内侧颞叶的邻近结构对于快速编码事实、地点和事件的新记忆的能力至关重要。当探索一个新的环境时，海马体必须将传入的感官体验与存储的表征进行协调，以形成新的记忆。我的长期研究目标是了解持续的行为如何塑造回路功能，以及这种能力如何在病理状态下改变。在这个研究计划中，我专注于行为状态和新奇形状电路在海马体中的功能。具体而言，该建议侧重于子场CA1，它作为海马的主要输出，以及它的输入，内嗅皮层（EC）的第三层和海马子场CA3。这些输入被认为是向CA1传达关于当前感官体验（EC）和内部存储表征（CA3）的信息。虽然这些区域已经成为许多研究的主题，但几乎没有人知道CA1在学习过程中如何动态地与CA3和EC耦合并整合输入。在这里，我建议使用多电极植入物，以记录同时在CA1，CA3，和EC的大鼠作为动物探索一个最初的新环境，并了解一个最初的新任务的神经活动。我的具体目标是：具体目标1：为了验证这一假设，在学习过程中，行为状态不断调节通过海马回路的信息流。具体目标2：检验学习增强海马回路中表征的时间对齐这一假设。实现这些特定目标将揭示行为和学习如何积极塑造大脑内嗅回路中的回路功能，更广泛地说，这项工作将有助于我们理解经验如何塑造大脑中的信息处理。这项研究是了解这些动力学在涉及海马结构的各种神经系统疾病中如何出错的先决条件。 海马体是大脑的一部分，对我们日常记忆新事实、地点和事件的能力很重要。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，但我们不了解海马体功能异常如何导致这些疾病中观察到的复杂行为变化。这项研究将帮助我们更好地了解海马电路的正常功能，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.