Imaging mitochondrial calcium dynamics in the central nervous system

Mitochondrial calcium handling is a particularly active research area in the neuroscience field, as it plays key roles in the regulation of several functions of the central nervous system, such as synaptic transmission and plasticity, astrocyte calcium signaling, neuronal activity… In the last few decades, a panel of techniques have been developed to measure mitochondrial calcium dynamics, relying mostly on photonic microscopy, and including synthetic sensors, hybrid sensors and genetically encoded calcium sensors. The goal of this review is to endow the reader with a deep knowledge of the historical and latest tools to monitor mitochondrial calcium events in the brain, as well as a comprehensive overview of the current state of the art in brain mitochondrial calcium signaling. We will discuss the main calcium probes used in the field, their mitochondrial targeting strategies, their key properties and major drawbacks. In addition, we will detail the main roles of mitochondrial calcium handling in neuronal tissues through an extended report of the recent studies using mitochondrial targeted calcium sensors in neuronal and astroglial cells, in vitro and in vivo.