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Among many distinct contributions made by Amiram Grinvald's group, the "Blue dyes" is a special gift for visualizing cortical population neuronal activity. The excitation wavelength of blue dyes has minimal overlap with the absorption of hemoglobin, and hence has minimal pulsation artifacts. This advantage leads to high signal-to-noise ratio optical recordings of cortical activity, with sensitivity as good as that of local field potential recordings. High sensitivity imaging allows for recording of spontaneous and evoked activity in single trials without spatial or temporal averaging, and has benefitted many scientists in their research projects. Single trial recording is particularly important for studying the cortex, because spontaneous and ongoing activities interact with sensory evoked events, creating rich dynamics in the wave patterns. Signal averaging in space and time would diminish the dynamic components in the patterns. Here, we discuss how the blue dyes help to achieve high-sensitivity voltage-sensitive dye imaging of spontaneous and evoked cortical activities. Spontaneous cortical activity has a constantly changing spatial pattern and temporal frequency, making it impossible to average in space and time. Amiran Grinvald's invention of blue dyes made it possible to examine the spatiotemporal patterns of cortical dynamics, about 15 years before the first useful genetically coded voltage proteins became available.

‘Blue’ voltage-sensitive dyes for studying spatiotemporal dynamics in the brain: visualizing cortical waves