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

• Applicant: Professorin Dr. Henrike Scholz
• Subject Area: Experimental and Theoretical Network Neuroscience ; Cognitive, Systems and Behavioural Neurobiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533236558

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.

• DFG Programme: Research Grants