Investigating the Importance of Calcium Control in Neurons by Micu1 to Learning and Emotional Regulation

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Calcium regulation by mitochondria is essential for maintaining cellular physiology. Studies have provided evidence that the Mitochrondrial Calcium Uniporter (MCU) regulates calcium uptake into mitochondria. Mitochondrial Calcium Uptake 1 (Micu1) has been demonstrated to play a critical role in closing the MCU at low levels of cytoplasmic calcium. Human patients carrying loss-of-function mutations in Micu1 suffer from muscle weakness, ataxia, and learning difficulties. However, despite numerous cell culture studies, there is limited information from knockout mice models. In this study, we investigate the roles of Micu1 in the brain by using brain specific Micu1 conditional knockout mice. Our pilot results show mice without Micu1 in the brain exhibit weak motor function, higher level of anxiety, and poor performance in water maze learning. We will further investigate the impact of Micu1 in brain architecture and Long-Term Potentiation. Next, to answer whether the altered anxiety and learning behavior we observed in Micu1 knockout mice is due to the weak motor function caused by impaired cerebellar development, we will cross Micu1 floxed mice with CAG-CreER mice to generate an inducible knockout mice model, which will allow us to investigate the role of Micu1 in anxiety and learning without confounding factors from development. We will assay behavior and brain architecture in these tamoxifen induced KO mice. To better understating whether restoration of Micu1 expression can rescue the anxiety and learning behavior, we will inject AAV viral vector to overexpress Micu1 in the hippocampus and measure mice behavior. For the last part of this project, we try to discover the possible pathways and mechanism by using RNA-seq to identify the differential gene expression in hippocampus between wildtype and Micu1 deficient mice, and compare the differential gene expression from knockout and Micu1 overexpressing mice. This analysis shall give us a better understanding of how Micu1 influences the downstream expression profile.

Project IDs

Project ID:PC10907-1520
External Project ID:MOST109-2320-B182-004
StatusFinished
Effective start/end date01/08/2031/07/21

Keywords

  • Micu1
  • mitochondria
  • hippocampus
  • learning
  • anxiety

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