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Mechanisms underlying reward-related synaptogenesis

奖励相关突触发生的机制

基本信息

批准号：
7894849
负责人：
Gloria E. Meredith
金额：
$ 30.8万
依托单位：
ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7894849
关键词：
Amphetamines Amygdaloid structure Animals Association Learning Behavior Biological Brain Brain region Burn injury Cells Clinical Complement Complex Cues Data Dendritic Spines Electron Microscopy Electrophysiology (science)Emotional Environment Excitatory Synapse Glutamates Goals Hippocampal Formation Hippocampus (Brain)Home environment Human In Vitro Individual Judgment Knowledge Learning Length Light Measures Mediating Medical Memory Modeling Modification Morphogenesis Neurons Pharmaceutical Preparations Physiological Process Pyramidal Cells Rattus Research Rewards Saline Sensory Shapes Signal Transduction Social Problems Source Stimulus Structure Symptoms Synapses Synaptic plasticity Techniques Translational Research Work base classical conditioning conditioned fear drug craving drug seeking behavior effective therapy experience hippocampal pyramidal neuron immunocytochemistry in vivo innovation memory retrieval neural circuit novel therapeutics preference presynaptic psychologic research study response stimulant abuse synaptogenesis transmission process

项目摘要

When amphetamine is repeatedly associated with the same environmental context, the environment becomes a powerful stimulus to elicit memories of the drug experience. These memories bring out a strong, physiological response, even in the absence of drug. Such associative learning is maladaptive and contributes to the poor judgment of individuals who crave the drug. However, we know surprisingly little of the synaptic modifications that shape drug-related memories, even though memory retrieval appears critical for the persistence of drug-seeking behavior. Conditioned place preference (CPP) is a model of cue-elicited drug seeking. When amphetamine is repeatedly paired with the same environment, rats learn to associate the rewarding effects of the drug with the cues provided by the environment. Our work has shown that the neural circuitry underlying this behavior could involve synaptic interactions between the hippocampal formation and basolateral amygdala (BLA). We have shown that amphetamine-induced CPP (AM PH CPP) is accompanied by increased synapses and a significant elevation in synaptic drive from the hippocampal formation. We believe that drug-seeking behavior therefore requires both structural and functional plasticity of BLA pyramidal cells to consolidate the learned association of drug and environment. We hypothesize further that this plasticity is mediated by the hippocampal formation. Through experiments outlined herein, we have set 2 specific aims: (1) The first will determine how AMPH CPP rewires BLA pyramidal neurons. The goal is to examine how CPP alters the eXCitatory and inhibitory synaptic complements of pyramidal neurons, using light and electron microscopy, immunocytochemistry and stereology. (2) In the scond, we will determine if AM PH CPP causes enhanced eXCitatory synaptic drive of BLA pyramidal neurons. The goals are to determine, using in vivo intracellular electrophysiological recordings, if BLA pyramidal neurons are subjected to abnormal excitatory drive, and if the hippocampal formation contributes to the excitation. The neuronal structure (dendrites and spines) of recorded BLA neurons will be studied to establish whether morphogenesis (increased spines, dendritic length and branching) is indicative of the strong increases in synaptic drive.

当安非他明反复与相同的环境背景联系在一起时，环境就会成为一种强大的刺激，引发人们对吸毒经历的记忆。即使在没有药物的情况下，这些记忆也会引起强烈的生理反应。这种联想学习是不适应的，导致渴望毒品的人判断力差。然而，令人惊讶的是，我们对形成药物相关记忆的突触修饰知之甚少，尽管记忆检索似乎对药物寻求行为的持久性至关重要。条件位置偏好（CPP）是一种线索诱导的药物寻找模型。当安非他明反复与相同的环境配对时，老鼠学会了将药物的奖励效果与环境提供的线索联系起来。我们的工作表明，这种行为背后的神经回路可能涉及海马体形成和基底外侧杏仁核（BLA）之间的突触相互作用。我们已经证明，安非他明诱导的CPP （AM PH CPP）伴随着突触的增加和海马形成的突触驱动的显著升高。因此，我们认为寻求药物的行为需要BLA锥体细胞的结构和功能可塑性来巩固药物和环境的习得关联。我们进一步假设这种可塑性是由海马体形成介导的。通过本文概述的实验，我们设定了两个具体目标：(1)首先将确定AMPH CPP如何重新连接BLA锥体神经元。目的是研究CPP如何改变锥体神经元的兴奋性和抑制性突触补体，使用光镜和电子显微镜，免疫细胞化学和立体学。(2)第二，我们将确定AM PH CPP是否会增强BLA锥体神经元的兴奋性突触驱动。目的是确定，使用体内细胞内电生理记录，如果BLA锥体神经元受到异常兴奋驱动，如果海马形成有助于兴奋。将研究记录的BLA神经元的神经元结构（树突和棘），以确定形态发生（棘、树突长度和分支增加）是否表明突触驱动的强烈增加。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Amphetamine-associated contextual learning is accompanied by structural and functional plasticity in the basolateral amygdala.

DOI：
10.1523/jneurosci.6165-09.2010
发表时间：
2010-03-31
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Rademacher DJ;Rosenkranz JA;Morshedi MM;Sullivan EM;Meredith GE
通讯作者：
Meredith GE

Increased synapses in the medial prefrontal cortex are associated with repeated amphetamine administration.