In this study, Drago and Davis show that inhibition of mitochondrial calcium entry in Drosophila mushroom body neurons during development impairs fly memory without altering their capacity to learn. In addition, they show associated defects in the structure and synaptic vesicle content of mushroom body neurons.
TSRI Scientists offer new insights how calcium in mitochondria can impact the development of the brain and adult cognition. In particular, the team showed in fruit flies, a widely used model system, that blocking a channel that brings calcium to the mitochondria, called “mitochondrial calcium uniporter,” causes memory impairment but does not alter learning capacity. “When we knocked down the activity of the uniporter, we found that flies have a deficit memory,” said Ron Davis, chair of the TSRI’s Department of Neuroscience. “Intact uniporter function is necessary for full and complete memory in the adult fly. What surprised us is that they were still able to learn – albeit with a fleeting memory. But we thought they wouldn’t be able to learn at all.”
The mitochondrial calcium uniporter protein, first identified in 2011, allows calcium ions to move from the cell’s interior into mitochondria. It is regulated by other proteins, MICU1, MICU2 and EMRE. Davis noted human patients with mutations in MICU1 can exhibit learning disabilities. “The new study’s conclusion is that mitochondrial calcium entry during development is necessary to establish the neuronal competency for supporting adult memory,” said TSRI Research Associate Ilaria Drago.
Inhibiting mitochondrial calcium uniporter function led to a decrease in the content of synaptic vesicles (where various neurotransmitters are stored) and an increase in the length of axons. While these structural problems were clearly observed, what they mean in terms of neuronal development remains tantalizingly unclear.
“The discovery of a developmental role for the mitochondrial calcium uniporter complex in regulating memory in adult flies is especially intriguing and deserves more exploration,” said Davis. http://www.scripps.edu/news/press/2016/20160826davis.html
http://www.cell.com/cell-reports/pdf/S2211-1247(16)31063-4.pdf
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