Notch-dependent microcircuit regulation of alcohol reward memory

酒精奖赏记忆的缺口依赖性微电路调节

基本信息

批准号：
9530374
负责人：
Karla R. Kaun
金额：
$ 35.63万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9530374
关键词：
Adult Affect Alcohol consumption Alcoholic Intoxication Alcohols Axon Behavior Behavioral Biological Assay Brain Cellular Structures Complex Cues Desire for food Development Disease Dopamine Drosophila genus Drosophila melanogaster Ethanol Feedback Fibrinogen Gene Expression Genes Genetic Transcription Genome Glutamates Goals Hippocampus (Brain)Individual Intoxication Investigation Lead Learning Mammals Measures Mediating Memory Molecular Molecular Target Mushroom Bodies Neuronal Plasticity Neurons Notch Signaling Pathway Output Peptides Pharmacology Pharmacotherapy Property Regulation Relapse Research Resolution Rewards Self Administration Signal Transduction Societies Structure Study models Transcriptional Regulation Work addiction alcohol availability alcohol craving alcohol response alcohol reward alcohol seeking behavior alcohol use disorder cholinergic craving effective therapy experience fly forward genetics genetic approach in vivo neural circuit neurogenetics neuroregulation notch protein novel optogenetics preference relating to nervous system response tool

项目摘要

PROJECT SUMMARY Despite its devastating impact on society, there are few effective treatments currently available for alcohol use disorder. The persistence of memories for the intoxication experience induces cravings, which can trigger relapse to alcohol use in recovering individuals. The neural and molecular mechanisms underlying these memories are complex, and despite recent advances, not well understood. This makes progress in finding pharmacological targets challenging. Investigation of these memories in the fruit fly, Drosophila melanogaster, presents a unique opportunity to gain a comprehensive understanding of the memories for alcohol reward at the level of genes, molecules, neurons and circuits. We propose to: 1) identify and investigate how simple central brain circuits function to form memories of the rewarding experience of alcohol intoxication, 2) compare how these circuits function for different forms of reward memory. Specifically, this research will reveal how dopaminergic microcircuits function to assign the rewarding properties of alcohol to associated cues, and how Notch signaling mediates neuronal plasticity within this circuit. This will be informative for understanding basic neural and molecular mechanisms underlying memory formation in addition to investigating how alcohol co-opts the brain's natural reward-related memory mechanisms to result in alcohol cravings.

项目概要尽管酒精对社会造成毁灭性影响，但目前几乎没有有效的治疗方法紊乱。对醉酒经历的持续记忆会引发渴望，从而引发康复者中再次饮酒。这些背后的神经和分子机制记忆是复杂的，尽管最近取得了进展，但人们还没有很好地理解。这使得寻找方面取得进展药理目标具有挑战性。对果蝇、果蝇中这些记忆的研究，提供了一个独特的机会来全面了解酒精奖励的记忆基因、分子、神经元和电路的水平。我们建议：1）识别并研究如何简单中枢脑回路的功能是形成对酒精中毒的有益经历的记忆，2）比较这些电路如何发挥不同形式的奖励记忆的作用。具体来说，这项研究将揭示多巴胺能微电路如何发挥作用来分配奖励酒精与相关线索的特性，以及 Notch 信号如何介导其中的神经元可塑性电路。这将为理解记忆背后的基本神经和分子机制提供信息除了研究酒精如何利用大脑的自然奖赏相关记忆之外，还研究了酒精的形成导致对酒精的渴望的机制。