Models of Signaling Mechanisms in LTP

LTP 中的信号机制模型

基本信息

批准号：
7118260
负责人：
WILLIAM R HOLMES
金额：
$ 22.56万
依托单位：
OHIO UNIVERSITY ATHENS
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2008-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7118260
关键词：
action potentials biological signal transduction dendrites excitatory aminoacid hippocampus laboratory rat learning long term potentiation memory synapses tissue /cell preparation voltage /patch clamp

项目摘要

DESCRIPTION (provided by applicant): Much of what we know, or suspect we know, about learning and memory comes from the study of long-term potentiation (LTP). LTP, first discovered in the hippocampus, is an increase in the strength or weight of synapses that can be induced by strong high frequency trains of action potentials. Despite years of study, it is still not known precisely how action potentials arriving al synapses in particular temporal patterns can generate cellular signals that trigger the biochemical reactions within dendritic spines that lead to long-term modifications of synaptic strength. This project will provide an understanding of this process by combining modeling and experimental studies to characterize the cellular signaling processes that occur with the development of long-term potentiation. Specific aims are: 1) To quantify how much of a change at individual synapses is necessary to account for the amount of potentiation observed in LTP, 2) To determine systematically stimulation protocols that are successful in eliciting LTP to allow identification of signaling cascades that particular protocols may activate, 3) To characterize the role of synaptic failures in initiating or hindering signaling processes, 4) To identify the differences in signaling mechanisms involved in NMDA-dependent and NMDA-independent forms of LTP in hippocampal area CA1, 5) To understand how molecular signaling complexes develop and function in dendritic spines. The combined modeling and experimental studies will provide critical insights into some of the outstanding questions about the mechanisms of cellular signaling in long-term potentiation. This knowledge can be used to understand mechanisms involved both in normal learning and memory and in the prevention or disruption of learning and memory that occurs with alcohol abuse. The methods used could have general applicability to signaling systems in other areas of physiology or for gene regulation.

描述（由申请人提供）：关于学习和记忆的我们所知道的或怀疑我们所知道的许多内容来自长期增强的研究（LTP）。 LTP最初是在海马中发现的，是突触的强度或重量的增加，可以通过强大的高频动作电位诱导。尽管经过多年的研究，但仍不知道在特定时间模式中到达Al突触的动作电位如何产生细胞信号，从而触发树突状棘中的生化反应，从而导致突触强度的长期修饰。该项目将通过结合建模和实验研究来表征与长期增强的发展发生的细胞信号传导过程，从而提供对这一过程的理解。具体目的是：1）量化在LTP中观察到的增强量所需的单个突触时需要进行多少变化，2）确定成功刺激LTP的系统刺激协议，以允许识别信号级联以识别特定协议可能激活的特定协议的信号级联，3）在启动突触启动方面的作用，3）在启动启动方面的作用，在4个启动过程中启动了四个启动的作用，4海马区域CA1中NMDA依赖性和NMDA独立的LTP形式，5）了解分子信号传导如何在树突状棘中发展和功能。合并的建模和实验研究将为有关长期增强中细胞信号的机制的一些杰出问题提供关键见解。这些知识可用于了解正常学习和记忆以及预防或破坏酒精滥用的学习和记忆中涉及的机制。所使用的方法可以在生理学其他领域或基因调节的其他领域具有一般适用性。