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.

细胞周期蛋白依赖性蛋白激酶5(Cdk5)是一种神经性蛋白激酶，参与多种不同过程。 在中枢神经系统中。CDK5已被证明可以调节新纹状体中的多巴胺信号和 是慢性可卡因暴露的分子靶点。我们打算研究CDK5在 腹侧纹状体(伏隔核)的谷氨酸能神经传递。特别值得关注的是 CDK5在药物滥用的主要靶点多巴胺信号转导中的作用。使用CRE/LoxP技术， 已经产生了条件性CDK5基因敲除小鼠，以允许对组织特异性基因敲除进行时间控制 CDK5。纹状体中cdk5的缺失对多巴胺信号通路的影响将通过 药理学方法结合定量免疫印迹。电生理特性 纹状体神经元的数量将在CDK5丢失后被定义。这些研究将在慢性病患者之后进行 可卡因暴露，以便更好地确定CDK5在新纹状体中的作用。