Novel optical approaches to study alcohol actions on GABA receptors

描述（由申请人提供）：我们建议使用新的光学方法来研究突触外GABAA受体，一个抑制性神经递质受体的子集，涉及急性酒精作用和适应慢性酒精暴露。这些新方法将使我们能够检查这些受体的池，由于技术原因，这些受体在实验中无法获得。具体目标一提出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的性质。第二个具体目标是利用一种新的光学电压传感方法来检查轴突和突触前末梢上的GABAR功能和药理学。这些结果将有助于理解乙醇和大脑镇静作用的分子决定因素，并应加速开发新的治疗方法，以解决酒精成瘾和酒精中毒期间发生的大脑功能的慢性变化。 公共卫生相关性：我们建议使用新的光学方法来研究突触外GABAA受体，抑制性神经递质受体的一个子集，涉及急性酒精作用和适应慢性酒精暴露。这些新方法将使我们能够检查这些受体的池，由于技术原因，这些受体在实验中无法获得。这些结果将有助于理解大脑中乙醇作用的分子决定因素，并应加速开发新的治疗方法，以解决酒精成瘾和酒精中毒期间发生的大脑功能的慢性变化。

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.