Function of mitochondria in the formation of neuronal plasticity underlying learning and memory

线粒体在学习和记忆神经元可塑性形成中的功能

• 批准号: 533236558
• 负责人: Professorin Dr. Henrike Scholz
• 金额: --
• 依托单位: AG Molecular Mechanisms of Addcitive Behaviors
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/533236558?language=en
• 关键词: Function; mitochondria; formation; neuronal; plasticity

Mitochondria are the power plants of the cell. They supply the cells with energy, regulate the balance of calcium ions and produce free oxygen radicals, which are physiologically relevant messenger in low concentrations. In neurons, many processes are energy dependent and depend on calcium ions. The loss of intact mitochondria is a hallmark of neurodegenerative diseases that are associated with memory loss. In addition to these cellular tasks of the mitochondria, however, it is not clear how in the healthy brain neuronal plasticity underlying learning and various forms of memory is regulated. Despite the fact that the function of mitochondria in the formation of neuronal plasticity in cellular systems has been and is being studied, the system-level knowledge of its function in the formation of short-term or long-term memory is far from complete. A very elegant system to study the influence of mitochondria on neuronal plasticity is the dopaminergic system in the fruit fly Drosophila melanogaster and its function in associative olfactory learning and memory. Here the dopaminergic neurons are known, which evaluate the external odor information and contribute to the formation of different forms of memory. Changing the function of different Miro interaction partners that selectively alter different aspects of mitochondria function, we want to investigate which mitochondrial functions in dopaminergic neurons are important in the formation of short- and long-term memory. We will analyze when damage to Miro-dependent mitochondrial function leads to memory alteration. Furthermore, we ask whether the Miro-dependent processes in different dopaminergic neurons regulate a similar form of neuronal plasticity. We will address what contributes to changes in memory at the cellular level before the death of neurons. We will investigate these questions using behavioral experiments and cellular imaging methods. With the experiments, we will find out which Miro-dependent functions of the mitochondria are important in the formation of different forms of memory. In addition, new insights into the different intrinsic properties of dopaminergic neurons will be gained. Ultimately, the findings might help to identify markers that predict the early onset of mitochondrial dysfunction in the brain.

线粒体是细胞的发电厂。它们为细胞提供能量，调节钙离子的平衡并产生自由基，这些自由基是低浓度的生理相关信使。在神经元中，许多过程都依赖于能量并依赖于钙离子。完整线粒体的丧失是与记忆丧失相关的神经退行性疾病的标志。然而，除了线粒体的这些细胞任务之外，尚不清楚健康大脑中学习和各种形式的记忆的神经元可塑性是如何受到调节的。尽管事实上线粒体在细胞系统中神经元可塑性形成中的功能已经并且正在被研究，但其在短期或长期记忆形成中的功能的系统水平知识还远未完成。研究线粒体对神经元可塑性影响的一个非常优雅的系统是果蝇果蝇的多巴胺能系统及其在联想嗅觉学习和记忆中的功能。这里的多巴胺能神经元是已知的，它们评估外部气味信息并有助于形成不同形式的记忆。通过改变不同 Miro 相互作用伙伴的功能，选择性地改变线粒体功能的不同方面，我们想要研究多巴胺能神经元中的哪些线粒体功能对于短期和长期记忆的形成很重要。我们将分析 Miro 依赖性线粒体功能的损伤何时会导致记忆改变。此外，我们询问不同多巴胺能神经元中的 Miro 依赖性过程是否调节类似形式的神经元可塑性。我们将探讨神经元死亡前细胞水平上记忆变化的原因。我们将使用行为实验和细胞成像方法来研究这些问题。通过实验，我们将发现线粒体的哪些 Miro 依赖性功能对于不同形式记忆的形成很重要。此外，还将获得对多巴胺能神经元不同内在特性的新见解。最终，这些发现可能有助于识别预测大脑线粒体功能障碍早期发生的标记物。