In vivo brain imaging of mitochondrial Ca2+ in neurodegenerative diseases with multiphoton microscopy.

Mitochondria are involved in a large number of essential roles related to neuronal function. Ca2+ handling by mitochondria is critical for many of these functions, including energy production and cellular fate. Conversely, mitochondrial Ca2+ mishandling has been related to a variety of neurodegenerative diseases. Investigating mitochondrial Ca2+ dynamics is essential for advancing our understanding of the role of intracellular mitochondrial Ca2+ signals in physiology and pathology. Improved Ca2+ indicators, and the ability to target them to different cells and compartments, have emerged as useful tools for analysis of Ca2+ signals in living organisms. Combined with state-of-the-art techniques such as multiphoton microscopy, they allow for the study of mitochondrial Ca2+ dynamics in vivo in mouse models of the disease. Here, we provide an overview of the Ca2+ transporters/ion channels in mitochondrial membranes, and the involvement of mitochondrial Ca2+ in neurodegenerative diseases followed by a summary of the main tools available to evaluate mitochondrial Ca2+ dynamics in vivo using the aforementioned technique.