Effects of Stress on Hippocampal Functioning

压力对海马功能的影响

• 批准号: 6607405
• 负责人: Jeansok John Kim
• 金额: $ 22.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607405
• 关键词: amygdala; behavior; cognition; hippocampus; long term potentiation; memory disorders; neural plasticity; neuroregulation; stress; tissue /cell culture

DESCRIPTION (provided by applicant): Memory impairments constitute a major problem in society. These occur naturally with aging and as a result of diseases (e.g., Alzheimer's disease), and are exacerbated by stress. The hippocampus, as part of a brain system necessary for the formation of stable declarative (or explicit) memory appears to be prominently susceptible to uncontrollable stress. Recent rodent studies demonstrate that stress interferes with learning of hippocarnpal-dependent spatial memory and alters the inducibility of long-term potentiation (LTP) and long-term depression (LTD)--two putative synaptic mechanisms of information storage-in the hippocampus. Other studies indicate that the amygdala is critically involved in coordinating stress-related behaviors and modulating hippocampal functioning. Our long-term goal is to understand the amygdalar mechanisms involved in mediating stress effects on hippocampal functioning.There are three specific aims of the project: (1) an IN VITRO ANALYSIS will investigate the role of the amygdala in mediating stress effects on hippocampal LTP/LTD; (2) a BEHAVIORAL ANALYSIS will examine the amygdalar mechanisms mediating stress-induced impairments in hippocampal-dependent spatial memory; and (3) a SINGLE UNIT ANALYSIS of hippocampal place cells will integrate stress effects on hippocampal plasticity and spatial memory. These related aims are designed to test our current working hypothesis that stress-induced alterations in hippocampal functioning are due to excessive activity exerted by the amygdala onto the hippocampus during stress.Data obtained from this project would be of significance (1) from a basic scientific perspective providing valuable information concerning how hippocampal plasticity might be regulated by naturalistic factors (such as stress) and the underlying mechanisms subserving stress effects on hippocampal functioning; and (2) from an applied perspective, providing important insights that will assist in developing therapeutic approaches to alleviate cognitive impairments associated with stress-induced ailments (such as anxiety, posttraumatic stress disorder, vascular dementia) that severely limit the quality of human life.

描述（由申请人提供）：记忆力障碍构成了社会的主要问题。这些自然发生在衰老和疾病（例如阿尔茨海默氏病）中，并因压力而加剧。作为形成稳定的声明性（或显式）记忆所必需的大脑系统的一部分，海马似乎很容易受到无法控制的压力的影响。最近的啮齿动物研究表明，压力会干扰河马依赖性空间记忆的学习，并改变长期增强（LTP）和长期抑郁症（LTD）的诱导性 - 两种推定的信息存储在海马中的推定突触机制。其他研究表明，杏仁核与协调应力相关行为并调节海马功能的行为至关重要。我们的长期目标是了解介导应力对海马功能的影响所涉及的杏仁核机制。该项目的三个具体目的：（1）体外分析将研究杏仁核在介导应力对海马型LTP/LTD介导应力效应中的作用； （2）行为分析将研究介导压力诱导的海马依赖性空间记忆中损伤的杏仁核机制； （3）对海马放置细胞的单个单位分析将使应力对海马可塑性和空间记忆的影响整合。这些相关目的旨在测试我们目前的工作假设，即压力引起的海马功能变化是由于杏仁核在压力期间施加了过度的活动，杏仁核在海马上施加的活动过多。从该项目获得的数据将具有显着性（1），这是从基本的科学角度来指导塑料的基本强度的塑料方面的重要性（1）。固定应力对海马功能的影响； （2）从应用的角度来看，提供重要的见解，这些见解将有助于开发治疗方法，以减轻与压力引起的疾病（例如焦虑，创伤后应激障碍，血管性痴呆）相关的认知障碍，从而严重限制了人类生活质量。