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：
9173692
负责人：
Karla R. Kaun
金额：
$ 35.6万
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/9173692
关键词：
Adult Affect Alcohol consumption Alcoholic Intoxication Alcohols Axon Behavior Biological Assay Brain Cellular Structures Complex Cues Development Disease Dopamine Drosophila genus Drosophila melanogaster Ethanol Feedback Fibrinogen Figs - dietary Gene Expression Genes 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 Pharmacotherapy Property Regulation Relapse Research Resolution Rewards Self Administration Signal Transduction Societies Structure Study models Transcriptional Regulation Work addiction alcohol craving alcohol reward alcohol seeking behavior alcohol use disorder cholinergic craving effective therapy experience fly forward genetics 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.

项目摘要尽管对社会的毁灭性影响，但目前几乎没有有效的饮酒治疗方法紊乱。对中毒体验的记忆的持续存在引起渴望，这可能会触发恢复个人的饮酒复发。这些基础的神经和分子机制回忆很复杂，尽管最近进步，但尚未得到充分理解。这在寻找方面取得了进展药理学目标具有挑战性。对果蝇中这些记忆的调查，果蝇Melanogaster，为在基因，分子，神经元和电路的水平。我们建议：1）识别并研究中央大脑电路的功能，形成了酗酒中含毒化的回忆的记忆，2）比较这些电路如何用于不同形式的奖励记忆。具体而言，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提示的特性，以及Notch信号如何介导此内神经元可塑性电路。这将是理解基本神经和分子机制的信息除了研究酒精如何选择大脑的自然奖励记忆之外，形成导致酒精渴望的机制。