Fluorescent proteins (FPs) have been engineered to produce an optical repor
t in response to cellular signals. FP fluorescence can be made directly sen
sitive to the chemical environment, via specific mutations of or around the
chromophore. Alternatively, FPs can be made indirectly sensitive to cellul
ar signals by their fusion to 'detector' proteins that respond to specific
cellular signals with structural rearrangements that act on the FP to alter
fluorescence. These optical sensors of membrane voltage, neurotransmitter
release, and intracellular messengers, including powerful new sensors of Ca
2+, cyclic nucleotides and nitric oxide, are likely to provide new insights
into the workings of cellular signals and of information processing in neu
ral circuits.