Circuit and Behavioral Functions of Hippocampal Subfield CA2

海马亚区 CA2 的回路和行为功能

• 批准号: 8660092
• 负责人: Kenneth Norman Kay
• 金额: $ 3.41万
• 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/8660092
• 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. 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(申请人提供)：海马体对于我们对事实、地点和事件的记忆进行编码的能力是必不可少的。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。在这个研究方案中，我们特别考虑了海马区CA1区的神经活动的基础，海马区是海马区的输出区域。CA1传统上被认为有两个主要的输入：内嗅皮层的第三层，或EC3，和海马亚区CA3。这些输入被认为是向CA1传达关于当前体验(EC3)和内部存储的表征(CA3)的信息。虽然这些上游区域已经被广泛研究，但对于CA1在学习过程中如何整合CA3和EC的输入知之甚少。我们认为，一个被称为CA2的特征不佳的邻近地区可能在这种整合中发挥了核心和快速的作用。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记忆任务(目标1和目标2)的大鼠CA1、CA2和CA3的神经活动。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(目标2)、表征(目标2B)和学习(目标2B)中的因果作用。我们的具体目标是：具体目标1：检验CA2激活先于EC3和CA3驱动的CA1网络模式的假设。具体目标2：检验CA2在CA1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。具体目的2B：验证CA2活性对于EC3驱动的CA1网络模式和表征以及正常的海马体记忆功能是必需的假设。实现这些特定的目标，除了为CA2提供功能外，还将揭示信息是如何在海马体电路中相对被忽视的部分处理的，CA2是大脑中一个从未确定其作用的区域。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，就像在与海马体相关的一系列神经精神障碍中遇到的那样。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症。 与公共健康相关：海马体是一种大脑结构，对我们记忆新事实、新地点和新事件的能力至关重要。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-然而，我们不知道海马体功能如何导致在这些障碍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的正常功能，特别是通过描述海马体中知之甚少的CA2区域的特征，从而为更有效地治疗这些涉及海马体的疾病提供基础。