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，这是一种抑制性神经递质受体，涉及急性酒精作用和慢性酒精暴露的适应。这些新方法将使我们能够检查由于技术原因在实验上无法获得的这些受体池。具体目的之一是利用激光光解技术来确定小脑神经元不同位置的非突触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测轴突和突触前末端的GABAR功能和药理学。这一结果将有助于理解乙醇的分子决定因素和大脑中的镇静作用，并应加快新疗法的发展，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.