Novel optical approaches to study alcohol actions on GABA receptors

研究酒精对 GABA 受体作用的新光学方法

基本信息

批准号：
8097596
负责人：
Thomas S Otis
金额：
$ 18.5万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8097596
关键词：
Acute Address Affect Alcohol consumption Alcohol dependence Alcoholic Intoxication Alcoholism Alcohols Anti-Anxiety Agents Antidepressive Agents Axon Barbiturates Benzodiazepines Brain Chloride Channels Chronic Confusion Consensus Dendrites Development Disease Drug effect disorder Electrophysiology (science)Ethanol Future GABA Receptor Genetic Predisposition to Disease Injury Ketamine Knowledge Lasers Lead Ligands Location Maps Measurement Measures Membrane Potentials Methods Molecular Monitor Neurons Neurotransmitter Receptor Optical Methods Optics Pharmaceutical Preparations Pharmacology Physiological Preparation Presynaptic Terminals Property Protein Isoforms Risk Factors Rohypnol Site Speed Spottings Synapses Synaptic Transmission Techniques Testing Therapeutic Time Work alcohol exposure alcohol measurement alcohol pharmacology alcohol research alcohol sensitivity barbituric acid salt base combat gamma-Aminobutyric Acid granule cell hypnotic innovation neuronal cell body neurosteroids neurotoxicity novel photolysis presynaptic public health relevance receptor receptor function response sedative sensor tool voltage

项目摘要

DESCRIPTION (provided by applicant): We propose to use novel optical methods to study extrasynaptic GABAA receptors, a subset of inhibitory neurotransmitter receptors implicated in both acute alcohol action and in adaptation to chronic alcohol exposure. These new methods will allow us to examine pools of these receptors that, for technical reasons, have been experimentally inaccessible. Specific aim one proposes to use laser-based photolysis techniques to determine the properties of non- synaptic GABARs in various locations on cerebellar neurons. The second specific aim makes use of a novel optical voltage sensing method to examine GABAR function and pharmacology on axons and presynaptic terminals. The results will facilitate understanding of the molecular determinants of ethanol and sedative action in the brain and should speed the development of new therapies to address alcohol addiction and the chronic changes in brain function that occur during alcoholism. PUBLIC HEALTH RELEVANCE: We propose to use novel optical methods to study extrasynaptic GABAA receptors, a subset of inhibitory neurotransmitter receptors implicated in both acute alcohol action and in adaptation to chronic alcohol exposure. These new methods will allow us to examine pools of these receptors that, for technical reasons, have been experimentally inaccessible. The results will facilitate understanding of the molecular determinants of ethanol action in the brain and should speed the development of new therapies to address alcohol addiction and the chronic changes in brain function that occur during alcoholism.

描述（由申请人提供）：我们建议使用新颖的光学方法来研究突触外 GABAA 受体，这是抑制性神经递质受体的一个子集，与急性酒精作用和对慢性酒精暴露的适应有关。这些新方法将使我们能够检查这些受体库，由于技术原因，这些受体库在实验上是无法获得的。具体目标是使用基于激光的光解技术来确定小脑神经元上不同位置的非突触 GABAR 的特性。第二个具体目标是利用一种新颖的光学电压传感方法来检查轴突和突触前末端的 GABAR 功能和药理学。这些结果将有助于了解乙醇和大脑镇静作用的分子决定因素，并应加速新疗法的开发，以解决酒精成瘾和酗酒期间发生的大脑功能慢性变化。公共健康相关性：我们建议使用新颖的光学方法来研究突触外 GABAA 受体，这是抑制性神经递质受体的一个子集，与急性酒精作用和对慢性酒精暴露的适应有关。这些新方法将使我们能够检查这些受体库，由于技术原因，这些受体库在实验上是无法获得的。这些结果将有助于了解乙醇在大脑中作用的分子决定因素，并应加速新疗法的开发，以解决酒精成瘾和酗酒期间发生的大脑功能慢性变化。