Synaptic plasticity, EtOH and backpropagating action potentials in NAcc

NAcc 中的突触可塑性、EtOH 和反向传播动作电位

基本信息

批准号：
7926900
负责人：
Gilles E MARTIN
金额：
$ 20.56万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-05 至 2012-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): It is now well established that acute and chronic alcohol alters the strength of synaptic transmission by modulating ion channels and receptors. A number of evidence suggest that the persistence of these changes, over days or weeks, explains, at least in part, alcohol long-lasting deleterious effects on behavior. Long-term potentiation (LTP) and depression (LTD) are the two most widely studied paradigms of such persistent synaptic alterations. To date, acute and chronic alcohol effects on LTP have been examined in structures of the limbic system (hippocampus, amygdala) and in the cortex. However, no study has been carried out in the nucleus accumbens (NAcc), a region believed to underlie the rewarding properties of all drugs of abuse, including that of alcohol. Furthermore, LTD has been largely ignored by all these studies. This leaves a number of questions regarding the cellular underpinnings of LTD regulation by alcohol. We hypothesize that LTD results from the interactions between synaptic potentials and backpropagating (b-APs), and that b-APs mediate EtOH effects on LTD. We believe that this attempt to bring together various fields of neurosciences (neuronal information processing and synaptic plasticity) will further our understanding of the cellular mechanisms employed by drugs of abuse to sustain their effects over long periods of time. The goal of this project is to examine the role of backpropagating action potentials in mediating the acute effects of alcohol on long- term potentiation depression (LTD), a well-known form of learning and memory paradigms. This study will be carried out in the nucleus accumbens, a major brain region responsible for the rewarding properties of all drugs of abuse. We believe this will represent an important step towards elucidating the cellular mechanisms underlying long-term persistent negative effects of alcohol on behavior.

描述（由申请人提供）：现在已经很好地确定，急性和慢性酒精通过调节离子通道和受体来改变突触传播的强度。许多证据表明，这些变化在几天或几周内的持久性至少部分解释了酒精对行为的长期有害影响。长期增强（LTP）和抑郁症（LTD）是这种持续突触改变的两个最广泛研究的范例。迄今为止，在边缘系统（海马，杏仁核）和皮层中已经检查了对LTP的急性和慢性酒精影响。但是，尚未在伏隔核（NACC）中进行研究，该地区据称是所有滥用药物（包括酒精）的奖励性质的基础。此外，所有这些研究都在很大程度上忽略了Ltd。这留下了许多关于Ltd调节的细胞基础的问题。我们假设LTD是由突触势与反向传播（B-APS）之间的相互作用引起的，并且B-APS介导了EtOH对LTD的影响。我们认为，这种试图将各种神经科学领域（神经元信息处理和突触可塑性）汇总在一起，将进一步了解我们对滥用药物在长期内维持其影响的细胞机制的理解。该项目的目的是研究反向传播动作电位在介导酒精对长期增强抑郁症（LTD）的急性影响方面的作用，这是一种众所周知的学习和记忆范式的形式。这项研究将在伏隔核中进行，这是一个主要的大脑区域，负责所有滥用药物的奖励性质。我们认为，这将代表阐明酒精行为长期持续负面影响的细胞机制迈出的重要一步。