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Published online by Cambridge University Press: 02 July 2020
Optical microscopy has been at the center of biological research, and neuroscience in particular, for a long time. For example, over one hundred years ago advances in microscopical techniques directly led to the discovery that neurons are in fact cells (the so-called ‘neuron doctrine’), and subsequently to the description of the high-resolution structure of the nervous system. More recently, the development of fluorescent indicators of cellular function, including Ca2+, Na+, and pH indicators, has made it possible to image not only the structure of neurons but also aspects of their function. The most important of these has been the measurement of intracellular free calcium concentration, [Ca2+]. Calcium is an important messenger molecule because it couples electrical excitation to biochemical signaling cascades. In addition, in neurons [Ca2+] is also a good indicator of local electrical excitation and thus [Ca2+] imaging allows the measurement of cellular excitability in subcellular compartments that are inaccessible to other methods.