Synaptic plasticity, EtOH and backpropagating action potentials in NAcc

描述（由申请人提供）：现在已经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递的强度。许多证据表明，这些变化持续数天或数周，至少在一定程度上解释了酒精对行为的长期有害影响。长期增强（LTP）和抑制（LTD）是这种持续性突触改变的两种最广泛研究的范式。迄今为止，已经在边缘系统（海马体、杏仁核）和皮层的结构中研究了急性和慢性酒精对LTP的影响。然而，目前还没有对伏隔核（NAcc）进行研究，该区域被认为是所有滥用药物（包括酒精）的奖励特性的基础。此外，有限责任公司在很大程度上被这些研究所忽视。这就留下了一些关于酒精对LTD调节的细胞基础的问题。我们假设LTD是由突触电位和反向传播（b-APs）之间的相互作用引起的，而b-APs介导了EtOH对LTD的影响。我们相信，这一尝试将神经科学的各个领域（神经元信息处理和突触可塑性）结合在一起，将进一步加深我们对滥用药物所使用的细胞机制的理解，以维持其长期的影响。本项目的目的是研究反向传播动作电位在酒精对长期增强性抑郁症（LTD）的急性效应中的作用，这是一种众所周知的学习和记忆范式。这项研究将在伏隔核进行，这是一个主要的大脑区域，负责所有滥用药物的奖励特性。我们相信这将是朝着阐明酒精对行为的长期持续负面影响的细胞机制迈出的重要一步。

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.