Notch-dependent microcircuit regulation of alcohol reward memory

项目摘要 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治疗方法可以用于酒精使用 disorder.对醉酒经历的记忆的持续会引起渴望，这可能会引发 恢复期个体的酒精使用复发。这些现象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，但还没有得到很好的理解。这在寻找 具有挑战性的药理学目标。对果蝇的这些记忆的研究， 提供了一个独特的机会，以获得全面了解记忆的酒精奖励， 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酒精中毒的奖励经验的记忆，2）比较 这些回路是如何运作不同形式的奖励记忆的。 具体来说，这项研究将揭示多巴胺能微电路如何发挥作用， 酒精的特性与相关的线索，以及Notch信号如何介导神经元可塑性， 电路.这将为理解记忆的基本神经和分子机制提供信息 除了研究酒精如何吸收大脑与奖励有关的自然记忆外， 导致酒精渴望的机制。

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.