Notch-dependent microcircuit regulation of alcohol reward memory

项目总结 尽管它对社会造成了毁灭性的影响，但目前几乎没有有效的酒精治疗方法 无序。对醉酒经历的持续记忆会引发渴望，这可能会触发 在康复者中再次饮酒。其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，但还没有被很好地理解。这使得在寻找 具有挑战性的药理目标。对果蝇黑腹果蝇这些记忆的研究， 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)确定和调查如何简单 中枢脑回路的功能是形成对酒精中毒有益经历的记忆，2)比较 这些电路如何对不同形式的奖励记忆起作用。 具体地说，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 酒精对相关线索的特性，以及Notch信号如何在其中调节神经元的可塑性 巡回赛。这将有助于理解记忆的基本神经和分子机制 形成除了研究酒精如何影响大脑的自然奖赏相关记忆 导致酒精渴求的机制。

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.