DNA Microarray Analysis of Neuronal Excitability

神经元兴奋性的 DNA 微阵列分析

• 批准号: 7066048
• 负责人: DONALD C COOPER
• 金额: $ 16.08万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-15 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7066048
• 关键词: amphetamines; behavioral /social science research tag; cocaine; drug addiction; drug receptors; gene expression; gene expression profiling; high throughput technology; hippocampus; laboratory mouse; laboratory rat; membrane channels; microarray technology; neural conduction; neural information processing; neural plasticity; neurogenetics; nucleus accumbens; prefrontal lobe /cortex; pyramidal cells; single cell analysis; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): The goal of this proposal is to establish a genetic profile of neuronal excitability as it relates to psychostimulant addiction. To accomplish this aim we will be using the most advanced oligonucleotide high density microarray technology combined with patch-clamp electrophysiology. Affymetrix Gene Chips allow for genome wide scans of the entire mouse genome for genes susceptible to chronic psychostimulant administration. In order to understand neural information procession in the brain reward circuitry as it relates to addiction, it is necessary to understand how individual neurons within this system code reward-related information. This project uses both DNA microarrays and patch-clamp electrophysiology to establish a molecular and functional characterization of nucleus accumbens, prefrontal cortical pyramidal neurons and ventral subicular hippocampal pyramidal neurons after repeated psychomotor stimulant injections in rats and mice. Specific aim 1 is to look for voltage and ligand-gated ion-channel genes that are subject to modulation by psychostimulants in the accumbens, subiculum and prefrontal cortical neurons. Specific aim 2 is to determine the functional manifestations of those changes within each structure. Specific aim 3 involves individual neuron gene expression profiling of electrophysiologically classified neurons (e.g. Interneurons and pyramidal bursting and nonbursting). Together these experiments will help us understand how drugs of abuse induce long-lasting neuroadaptations within the brain reward circuitry. With greater understanding of addiction-associated plasticity it may be possible to develop pharmacological or gene profiling strategies to screen for addiction vulnerability and possible therapeutic interventions.

描述（由申请人提供）：该提案的目的是建立与精神刺激成瘾有关的神经元兴奋性的遗传特征。为了实现这一目标，我们将使用最先进的寡核苷酸高密度微阵列技术与贴片钳电生理学结合使用。 Affymetrix基因芯片允许对易受慢性精神刺激性给药的基因进行整个小鼠基因组的基因组扫描。为了了解与成瘾有关的大脑奖励电路中的神经信息游行，有必要了解该系统代码奖励相关信息中的单个神经元。该项目同时使用DNA微阵列和斑板钳电生理学来建立伏伏核，前额叶皮质锥体神经元和腹侧腹侧锥形神经元的分子和功能表征，这是在重复的心理运动刺激性注射大鼠和小鼠后。具体目的1是寻找伏伏刺激性，亚表皮和前额叶皮质神经元的精神刺激物调节的电压和配体门控的离子通道基因。具体目标2是确定每个结构内这些变化的功能表现。特定的目标3涉及电生理分类神经元（例如，中间神经元和金字塔爆发和非爆炸）的单个神经元基因表达分析。这些实验将共同帮助我们了解滥用药物如何在大脑奖励电路中引起长期的神经适应。通过更了解与成瘾相关的可塑性，可能有可能制定药理学或基因分析策略，以筛选成瘾脆弱性和可能的​​治疗干预措施。