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Abstract

Recording activity from identified populations of neurons is a central
goal of neuroscience. Changes in membrane depolarization, particularly
action potentials, are the most important features of neural physiology
to extract, although ions, neurotransmitters, neuromodulators, second
messengers, and the activation state of specific proteins are also
crucial. Modern fluorescence microscopy provides the basis for such
activity mapping, through multi-photon imaging and other optical
schemes. Probes remain the rate-limiting step for progress in this
field: they should be bright and photostable, and ideally come in
multiple colors. Only protein-based reagents permit chronic imaging
from genetically specified cells. Here we review recent progress in the
design, optimization and deployment of genetically encoded indicators
for calcium ions (a proxy for action potentials), membrane potential,
and neurotransmitters. We highlight seminal experiments, and present an
outlook for future progress.