Behavioral and neural characterization of a pharmacological tool to regulate mitochondrial calcium influx in vivo (2024)

Undergraduate: Elizabeth Banyas

Faculty Advisor: Antony Abraham
Department: Research Triangle Institute Center for Drug Discovery, University of Chapel Hill Psychology and Neuroscience

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It is widely recognized that mitochondria play a crucial role in neural energy processes, earning them the title of "the powerhouse of the cell. Research indicates that mitochondrial ATP levels are controlled by the influx of calcium (Ca2+). The gene micu1, responsible for encoding mitochondrial proteins, regulates the entry of Ca2+ through a mitochondrial calcium uniporter (MCU) complex. Prolonged exposure to cocaine leads to changes in both the structure and function of neural mitochondria. However, current technologies for accessing, observing, and manipulating mitochondria in vivo are limited._x000D_
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This project aims to validate the direct influence of a MICU1-targeting drug, Mcui4, and enhance the understanding of the molecular pathways involved in modulating neural mitochondrial activities. We hypothesize that blocking Ca2+ structures in mitochondria during cocaine exposure should block cocaine-mediated changes. As a result of cocaine exposure, dopamine (DA) should be released from ventral tegmental area axons and modulated by the MCU complex in DA neuron axon terminals in the nucleus accumbens. Overall, the results of this research will contribute to the development of cocaine use disorder treatments.