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

开放式酒吧分析：一种检查果蝇动机反应和药物滥用的新操作范例

• 批准号: 10646237
• 负责人: John Hernandez
• 金额: $ 7.18万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10646237
• 关键词: Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcoholism; Alcohols; Animals; Behavior; Behavioral; Behavioral Research; Biochemical; Biological Assay; Biological Models; Brain; Calcium; Cells; Complex; Computer Vision Systems; Cues; Data; Desire for food; Development; Drosophila genus; Drosophila melanogaster; Escalator; Ethanol; Factor Analysis; Genetic; Goals; Heavy Drinking; Heterogeneity; Image; Individual; Individual Differences; Individuality; Intervention; Learning; Locomotion; Machine Learning; Maps; Memory; Mission; Modeling; Motivation; Mushroom Bodies; National Institute on Alcohol Abuse and Alcoholism; Neurons; Output; Pattern; Persons; Pharmaceutical Preparations; Phenotype; Play; Population; Resolution; Rewards; Role; Self Administration; Structure; Substance abuse problem; System; Testing; Time; Variant; Vertebrates; Volatilization; Work; addiction; alcohol exposure; alcohol memory; alcohol related problem; alcohol research; alcohol response; alcohol seeking behavior; alcohol use disorder; awake; behavior prediction; body system; data pipeline; dopaminergic neuron; drinking; drinking behavior; effective therapy; experimental study; fly; individual variation; memory encoding; neural; neural circuit; neuromechanism; neurophysiology; novel; optogenetics; permissiveness; preference; response; two-photon

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.

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酒精寻求行为。 然而，回路的身份和功能的个体差异，在酒精自我管理行为 仍然没有被很好地理解。这个提议的目的是识别微妙的行为特征，基本的电路 易处理模型系统中酒精偏好的基本原理和神经生理学动力学 果蝇Aim 1将采用计算机视觉和机器学习方法来识别细微的 与酒精偏好和酒精回避有关的行为。在这个目标中，我假设动物， 表达酒精偏好显示增强的寻求行为，特别是对酒精自我的反应。 较低的酒精偏好将通过避免和减少的运动来表现。目的 2将采用热失活，使用GAL 4/UAS系统，学习和记忆的大脑回路， 在编码酒精偏好中起着直接的作用。在这个目标中，我假设我们的 已确定的学习和记忆脑回路将直接抑制果蝇对酒精偏好的表达。 目标3将研究我们识别的回路的神经生理动力学在酒精和酒精之间的差异。 偏爱者和禁欲者。我假设，在我确定的回路中，酒精暴露将导致 我们将在酒精偏好者中观察到相反的神经生理反应。 这项工作将提供一个框架，预测一般电路原则升级的酒精自我， 这与NIAAA支持行为研究的使命一致 关于酒精中毒和酒精相关问题的原因。