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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，我们所知道的，或者我们认为我们所知道的，大部分都来自于长期增强（LTP）的研究。LTP首先在海马体中被发现，它是一种突触强度或重量的增加，可以由高强度的高频动作电位引起。尽管经过多年的研究，人们仍然不清楚在特定时间模式下到达突触的动作电位如何产生细胞信号，触发树突棘内的生化反应，从而导致突触强度的长期改变。本项目将通过结合模型和实验研究来描述长期增强过程中发生的细胞信号传导过程，从而提供对这一过程的理解。