Regional actions of general anesthetics in inhibitory hippocampal networks

全身麻醉药在抑制性海马网络中的区域作用

基本信息

批准号：
8214607
负责人：
Uwe Rudolph
金额：
$ 44.96万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8214607
关键词：
Alzheimer&apos s Disease Amnesia Anesthetics Animal Model Awareness Behavior Behavioral Behavioral Genetics Benzodiazepines Brain region Cell physiology Data Dendrites Development Diazepam Drug effect disorder Etomidate Event Excitatory Synapse Extinction (Psychology)Feedback Fright Funding GABA-A Receptor General Anesthesia General anesthetic drugs Generations Genetic Hippocampus (Brain)Incidence Knock-out Laboratories Lead Learning Long-Term Potentiation Measurement Measures Mediating Memory Methods Midazolam Modeling Mus Neuronal Plasticity Neurons Pattern Performance Pharmaceutical Preparations Physiological Play Point Mutation Positioning Attribute Post-Traumatic Stress Disorders Process Pyramidal Cells Regulation Role Study models Synapses Synaptic Transmission Techniques Testing Time Translating United States Universities Water Wild Type Mouse abstracting base conditioned fear dentate gyrus experience granule cell hippocampal pyramidal neuron hippocampal subregions hypnotic improved information processing learning extinction memory encoding memory recall morris water maze novel novel therapeutics object recognition receptor research study sedative synaptic inhibition

项目摘要

Project Summary/Abstract RATIONALE: This is an application for funding of a study on the role of extrasynaptic alpha5-containing GABA-A receptors in the CA1 and CA3 subfields and in dentate gyrus and inhibitory hippocampal networks for the amnestic action of the general anesthetic etomidate, using a combination of genetic, behavioral and electrophysiological methods. In his previous position at the University of Zurich, by the generation and analysis of mice carrying a point mutation in the alpha5 subunit of the GABA-A receptor, which leads to a partial knockout of this subunit, the applicant's group demonstrated that GABA-A receptors containing the alpha5 subunit modulate defined memory functions. Using novel animal models that have recently been developed in the applicant's laboratory, we propose to characterize the physiological and pharmacological functions of the alpha5 subunit in CA1 and CA3 pyramidal cells and dentate gyrus granule cells of the hippocampus, respectively, using a combination of genetic, electrophysiological, pharmacological, and behavioral techniques, with the major focus on the mechanism of the amnestic actions of general anesthetics.

项目摘要/摘要理由：这是一项申请，用于资助有关含抗肌外α5的作用的研究 CA1和CA3子场以及齿状回和抑制性海马网络中的GABA-A受体为了使用遗传，行为和行为和电生理方法。在他以前在苏黎世大学的职位，这一代人和分析GABA-A受体α5亚基中携带点突变的小鼠，这导致了A 该亚基的部分敲除，申请人的群体证明了含有的GABA-A受体 Alpha5亚基调制定义的内存功能。使用最近的动物模型我们在申请人的实验室中开发，我们建议表征生理和药理 CA1和CA3锥体细胞中的alpha5亚基的功能以及齿状回颗粒细胞的功能海马分别使用遗传，电生理，药理和行为技术，主要关注一般动作的机制麻醉药。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Zolpidem Activation of Alpha 1-Containing GABAA Receptors Selectively Inhibits High Frequency Action Potential Firing of Cortical Neurons.

唑吡坦激活含 Alpha 1 的 GABAA 受体选择性抑制皮质神经元的高频动作电位放电。

DOI：
10.3389/fphar.2018.01523
发表时间：
2018
期刊：
Frontiers in pharmacology
影响因子：
5.6
作者：
Neumann,Elena;Rudolph,Uwe;Knutson,DanielE;Li,Guanguan;Cook,JamesM;Hentschke,Harald;Antkowiak,Bernd;Drexler,Berthold
通讯作者：
Drexler,Berthold

GABAA receptor subtypes: Therapeutic potential in Down syndrome, affective disorders, schizophrenia, and autism.