Open bar assay: A novel operant paradigm for examining motivated response and substance abuse in Drosophila melanogaster

项目摘要/摘要 酒精偏好和自我管理的个体差异促进了强迫性饮酒行为。 然而，在酒精自我给药行为中潜在的个体差异的回路身份和功能 仍然没有被很好地理解。这项建议的目标是识别微妙的行为特征、基本电路 易处理模型系统中酒精偏好的原理和神经生理动力学 黑腹果蝇。目标1将使用计算机视觉和机器学习方法来识别细微的 与饮酒偏好和避免饮酒有关的行为。在这个目标中，我假设动物 表现出的酒精偏好增强了寻找行为，特别是对酒精自我的反应 而较低的酒精偏好将通过回避和减少运动来体现。目标 2将使用GAL4/UAS系统对学习和记忆大脑回路进行生热失活 相信在编码酒精偏好方面起着直接作用。在这个目标中，我假设我们的 已确定的学习和记忆大脑回路将直接抑制果蝇对酒精偏好的表达。 目标3将研究我们已识别的神经回路的神经生理动力学在酒精和酒精之间的差异。 优选者和弃权者。我假设，在我确定的回路中，酒精暴露会导致强健的 在喜欢饮酒的人中，我们将观察到相反的神经生理学反应。 这项工作将为预测酒精自身升级的一般电路原理提供一个框架 在更复杂的大脑中进行管理，这与NIAAA支持行为研究的使命一致 关于酒精中毒的原因和与酒精有关的问题。

PROJECT SUMMARY/ ABSTRACT Individual variation in alcohol preference and self-administration facilitates compulsive alcohol seeking behavior. However, the circuit identity and function underlying individual variability in alcohol self-administration behaviors is still not well understood. The goal of this proposal is to identify subtle behavioral features, fundamental circuitry principles and neurophysiological dynamics underlying alcohol preference in the tractable model system Drosophila melanogaster. Aim 1 will employ a computer vision and machine learning approach to identify subtle behaviors that relate to alcohol preference and alcohol avoidance. In this Aim I hypothesize that animals that express alcohol preference display enhanced seeking behavior, in particular in response to alcohol self- administration whereas lower alcohol preference will manifest through avoidance and reduced locomotion. Aim 2 will employ thermogenetic inactivation, using the GAL4/UAS system, of learning and memory brain circuits we believe play a direct role in encoding alcohol preference. In this Aim I hypothesize that inactivation of our identified learning and memory brain circuits will directly suppress the expression of alcohol preference in flies. Aim 3 will investigate how the neurophysiological dynamics of our identified circuit differs between alcohol preferers and abstainers. I hypothesize that, in my identified circuit, alcohol exposure will result in robust neurophysiological responses in alcohol-preferers and that we will observe the opposite in alcohol abstainers. This work will provide a framework for predicting general circuit principles for escalation of alcohol self- administration in more complex brains, which is in alignment with NIAAA’s mission to support behavioral research on the causes of alcoholism and alcohol-related problems.