Circuit and Behavioral Functions of Hippocampal Subfield CA2

海马亚区 CA2 的回路和行为功能

• 批准号: 8314724
• 负责人: Kenneth Norman Kay
• 金额: $ 3.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8314724
• 关键词: Activation Analysis; Address; Animals; Axon; Behavior; Behavioral; Brain; Brain region; Clinical; Cognition; Complex; Data; Dementia; Disease; Event; Frequencies; Functional disorder; Future; Goals; Hippocampus (Brain); Implanted Electrodes; Learning; Link; Memory; Memory Loss; Mental Depression; Mental disorders; Mood Disorders; Neurons; Output; Pathway interactions; Pattern; Physiology; Process; Rattus; Reporting; Research; Research Proposals; Role; Route; Schizophrenia; Sensory; Sensory Process; Structure; Synapses; Task Performances; Testing; Travel; addiction; age related; autism spectrum disorder; base; effective therapy; entorhinal cortex; experience; memory encoding; millisecond; neglect; neural circuit; neuropsychiatry; relating to nervous system; research study; tool

DESCRIPTION (provided by applicant): The hippocampus is essential for our ability to encode memories for facts, places, and events. My long-term research goal is to understand how neural activity in specific neural circuits gives rise to complex behaviors, and how these circuits and behaviors are altered in pathological states. In this research proposal, we specifically consider the basis of neural activity at hippocampal subfield CA1, the output region of the hippocampus. CA1 has traditionally been studied as having two main inputs: layer III of the entorhinal cortex, or EC3, and hippocampal subfield CA3. These inputs are thought to convey information to CA1 about current experience (EC3) and internally stored representations (CA3). While these upstream regions have been extensively studied, little is known about how CA1 integrates input from CA3 and EC during learning. We believe a poorly characterized neighboring region called CA2 may have a central and rapid role in this integration. To address this possibility, we will use multi-electrode implants to record neural activity in CA1, CA2, and CA3 of rats engaged in a hippocampus-dependent memory task (Aim 1 and Aim 2). We will also use precise tools for electrophysiological manipulation to establish causal roles of CA2 in hippocampal neural activity patterns (Aim 2), representations (Aim 2B), and learning (Aim 2B). Our specific aims are: Specific Aim 1: To test the hypothesis that CA2 activation precedes both EC3- and CA3- driven network patterns at CA1. Specific Aim 2: To test the hypothesis that CA2 controls EC3- and CA3- driven network patterns at CA1. Specific Aim 2A: To test the hypothesis that CA2 activation is sufficient for initiating CA3- driven network patterns at CA1. Specific Aim 2B: To test the hypothesis that CA2 activity is necessary for EC3- driven network patterns and representations at CA1, and for normal hippocampal memory function. Accomplishing these Specific Aims will reveal how information is processed in a relatively neglected part of the hippocampal circuit, in addition to providing functional roles for CA2, a region of the brain whose role has never been established. This research is necessary for understanding the origins and consequences of hippocampal dysfunction, as encountered in the range of neuropsychiatric disorders linked to the hippocampus. These disorders include schizophrenia, mood disorders, autism spectrum disorders, and dementia. PUBLIC HEALTH RELEVANCE: The hippocampus is a brain structure that is critical for our 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 - yet we do not understand how hippocampal function contributes to the complex behavioral changes observed in these disorders. The proposed research will help us better understand the normal functioning of the hippocampus, specifically by characterizing a poorly understood region of the hippocampus known as CA2, and thus provide the basis for more effective treatments of these disorders involving the hippocampus.

描述（由申请人提供）：海马体对我们对事实、地点和事件进行记忆编码的能力至关重要。我的长期研究目标是了解特定神经回路中的神经活动如何产生复杂的行为，以及这些回路和行为在病理状态下是如何改变的。在本研究方案中，我们特别考虑海马输出区CA1的神经活动基础。CA1传统上被研究为有两个主要输入：内嗅皮层的第三层，或EC3，和海马亚区CA3。这些输入被认为向CA1传递有关当前经验（EC3）和内部存储表示（CA3）的信息。虽然这些上游区域已被广泛研究，但对于CA1如何在学习过程中整合来自CA3和EC的输入，我们知之甚少。我们认为，一个被称为CA2的特征较差的邻近区域可能在这种整合中起着核心和快速的作用。为了解决这种可能性，我们将使用多电极植入来记录参与海马体依赖性记忆任务的大鼠CA1， CA2和CA3的神经活动（目的1和目的2）。我们还将使用精确的电生理操作工具来确定CA2在海马神经活动模式（Aim 2）、表征（Aim 2B）和学习（Aim 2B）中的因果作用。我们的具体目标是：具体目标1：测试CA2激活先于EC3和CA3驱动的CA1网络模式的假设。具体目标2：验证CA2在CA1上控制EC3和CA3驱动的网络模式的假设。具体目标2A：验证CA2激活足以在CA1启动CA3驱动的网络模式的假设。特定目的2B：验证CA2活性对于EC3驱动的网络模式和CA1的表征以及正常的海马记忆功能是必要的假设。完成这些特定目标将揭示信息是如何在海马体回路中相对被忽视的部分处理的，除了提供CA2的功能作用之外，CA2是大脑中一个从未被确定的区域。这项研究对于理解海马体功能障碍的起源和后果是必要的，因为在与海马体相关的神经精神疾病的范围内遇到。这些疾病包括精神分裂症、情绪障碍、自闭症谱系障碍和痴呆症。