Circuit and Behavioral Functions of Hippocampal Subfield CA2

海马亚区 CA2 的回路和行为功能

• 批准号: 8607848
• 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/8607848
• 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; public health relevance; 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.

描述（申请人提供）：海马体对于我们对事实、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引起复杂行为，以及这些回路和行为在病理状态下如何改变。在这项研究计划中，我们特别考虑了海马CA1区（海马的输出区域）神经活动的基础。传统上，CA 1被研究为有两个主要输入：内嗅皮质的第三层（EC 3）和海马子区CA 3。这些输入被认为向CA1传达关于当前经验（EC3）和内部存储的表征（CA3）的信息。虽然这些上游区域已被广泛研究，但很少有人知道CA1如何在学习过程中整合来自CA3和EC的输入。我们认为，一个被称为CA2的特征不明显的邻近地区可能在这种整合中发挥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物来记录参与海马依赖性记忆任务（Aim 1和Aim 2）的大鼠的CA1，CA2和CA3中的神经活动。我们还将使用精确的电生理操作工具来建立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：测试假设CA2激活之前的EC3和CA3驱动的网络模式在CA1。具体目标2：检验CA 2控制CA 1处EC 3和CA 3驱动的网络模式的假设。 具体目标2A：检验CA 2激活足以在CA 1启动CA 3驱动的网络模式的假设。具体目标2B：为了验证这一假设，即CA2活动是必要的EC3驱动的网络模式和代表在CA1，并为正常的海马记忆功能。实现这些特定目标将揭示信息是如何在海马回路中相对被忽视的部分进行处理的，除了为CA2提供功能角色之外，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功能障碍的起源和后果是必要的，因为在与海马相关的神经精神疾病的范围内遇到。这些障碍包括精神分裂症、情绪障碍、自闭症谱系障碍和痴呆。