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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/7926900
• 关键词: Action Potentials; Acute; Alcohols; Amygdaloid structure; Area; Behavior; Brain region; Cells; Characteristics; Chronic; Coupled; Drug Addiction; Elements; Fire - disasters; Frequencies; Glutamates; Goals; Hippocampus (Brain); Invaded; Ion Channel; Learning; Left; Limbic System; Long-Term Potentiation; Mediating; Membrane; Membrane Potentials; Memory; Mental Depression; Molecular; Neurons; Neurosciences; Nucleus Accumbens; Output; Pharmaceutical Preparations; Pilot Projects; Preparation; Property; Regulation; Relapse; Reporting; Rest; Rewards; Role; Slice; Structure; Synapses; Synaptic Potentials; Synaptic Transmission; Synaptic plasticity; Testing; Time; Travel; alcohol effect; base; drug of abuse; information processing; interest; knockout animal; neuronal cell body; patch clamp; postsynaptic; presynaptic; receptor; stem; study characteristics; tool

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）：现已明确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，至少部分解释了酒精对行为的长期有害影响。长时程增强（LTP）和抑制（LTD）是这种持续性突触改变研究最广泛的两个范例。迄今为止，已经在边缘系统（海马、杏仁核）和皮质结构中检查了酒精对 LTP 的急性和慢性影响。然而，尚未对伏隔核（NAcc）进行研究，该区域被认为是所有滥用药物（包括酒精）的有益特性的基础。此外，所有这些研究在很大程度上都忽略了LTD。这留下了许多关于酒精调节LTD的细胞基础的问题。我们假设 LTD 是突触电位和反向传播 (b-AP) 之间相互作用的结果，并且 b-AP 介导 EtOH 对 LTD 的影响。我们相信，这种将神经科学各个领域（神经元信息处理和突触可塑性）结合在一起的尝试将进一步加深我们对滥用药物长期维持其作用的细胞机制的理解。该项目的目标是研究反向传播动作电位在调节酒精对长期增强抑制（LTD）的急性影响中的作用，长期增强抑制是一种众所周知的学习和记忆范式。这项研究将在伏隔核中进行，伏隔核是负责所有滥用药物的奖励特性的主要大脑区域。我们相信，这将是阐明酒精对行为长期持续负面影响的细胞机制的重要一步。

项目成果

Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways.

多巴胺受体差异控制酗酒介导的伏隔核心核直接和间接通路的突触可塑性。

• 发表时间: 2017-05-31
• 作者: Ji, Xincai;Saha, Sucharita;Kolpakova, Jenya;Guildford, Melissa;Tapper, Andrew R;Martin, Gilles E
• 通讯作者: Martin, Gilles E

Functional and structural deficits at accumbens synapses in a mouse model of Fragile X

脆性 X 小鼠模型伏隔突触的功能和结构缺陷

• DOI: 10.3389/fncel.2015.00100
• 发表时间: 2015
• 期刊: Frontiers in Cellular Neuroscience
• 影响因子: 5.3
• 作者: Neuhofer D;Henstridge CM;Dudok B;Sepers M;Lassalle O;Katona I;Manzoni OJ
• 通讯作者: Manzoni OJ