MINORITY PREDOCTORAL FELLOWSHIP PROGRAM

少数族裔博士前奖学金计划

• 批准号: 7338000
• 负责人: David Roger Benavides
• 金额: $ 3.14万
• 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: 2005-10-01 至 2008-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7338000
• 关键词: Acute; Animals; Biology; Cell model; Cells; Chronic; Cocaine; Corpus striatum structure; Cyclin-Dependent Kinase 5; Dopamine; Dopamine Receptor; Drug Addiction; Fellowship Program; Foundations; Genetic Models; Glutamates; Immunoblotting; Investigation; Knock-out; Knockout Mice; Learning; Long-Term Depression; Long-Term Potentiation; Mediating; Memory; Minority; Molecular Target; Nature; Neostriatum; Neuraxis; Neurons; Nucleus Accumbens; Numbers; Phosphorylation; Phosphotransferases; Play; Preparation; Process; Property; Protein Dephosphorylation; Regulation; Role; Signal Transduction; Signal Transduction Pathway; Slice; Synapses; Technology; Tissues; Ventral Striatum; drug of abuse; extracellular; interest; neuronal excitability; neurotransmission; novel; pre-doctoral; response; synaptic function

Cyclin-dependent kinase 5 (Cdk5) is a neuronal kinase that has been implicated in many diverse processes in the central nervous system. Cdk5 has been shownto regulate dopamine signaling in the neostriatum and is a molecular target of chronic cocaine exposure. We intend to investigate the role Cdk5 plays in glutamtatergic neurotransmission in the ventral striatum (nucleus accumbens). Of particular interest is the role of Cdk5 in dopamine signaling, the main target of drugs of abuse. Using Cre/loxP technology, a conditional cdk5 knockout mouse has been generated to allow temporal control of tissue-specific knockout of Cdk5. The effect of striatal loss of Cdk5 on dopamine signaling pathwaywill be assessed using a pharmacological approach combined with quantitative immunoblotting. The electrpphysiological properties of striatal neurons will be defined following loss of Cdk5. These studies will be conducted following chronic cocaine exposure, in order to better define the role of Cdk5 in the neostriatum.

Cyclin依赖性激酶5（CDK5）是一种神经元激酶，与许多多种过程有关 在中枢神经系统中。已显示CDK5调节新纹状体中的多巴胺信号传导 是慢性可卡因暴露的分子靶标。我们打算研究CDK5在 腹侧纹状体（伏隔核）中的谷氨酸神经传递。特别感兴趣的是 CDK5在多巴胺信号传导中的作用，这是滥用药物的主要目标。使用CRE/LOXP技术， 有条件的CDK5敲除小鼠已经生成，以允许对组织特异性敲除的时间控制 CDK5。 CDK5纹状体损失对多巴胺信号传导途径的影响将使用A评估 药理学方法与定量免疫印迹结合。电子生理特性 CDK5丢失后，将定义纹状体神经元的含量。这些研究将在慢性之后进行 可卡因暴露，以更好地定义CDK5在新纹状体中的作用。