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Analytical Chemistry

Fluorescent Protein Calcium Sensors Image Neuron Activity

Ultrasensitive protein sensors perform as well as synthetic dye indicators

by Celia Henry Arnaud
July 22, 2013 | A version of this story appeared in Volume 91, Issue 29

When neurons fire in the nervous system, calcium levels spike inside the cells. Imaging experiments that detect these changes can be used to track neuronal activity. In many cases, scientists would prefer to use protein sensors for the monitoring because they can be targeted to particular cell types and used over long periods. Researchers have previously developed fluorescent protein calcium sensors, but so far those proteins haven’t been as sensitive as synthetic calcium indicators. The Genetically-Encoded Neuronal Indicator & Effector (GENIE) Project, based at Howard Hughes Medical Institute’s Janelia Farm Research Campus, in Virginia, has now developed a family of fluorescent sensor proteins that match the performance of the synthetic counterparts (Nature 2013, DOI: 10.1038/nature12354). The researchers engineered the protein sensors by performing multiple rounds of mutation and neuronal screening of a protein complex called GCaMP. They picked three of the most sensitive sensors for in vivo characterization and used them to image neuronal activity in cultured cells and in live mice, zebrafish, and fruit flies. The new GCaMP6 sensors performed as well as Oregon Green Bapta-1-AM, a commonly used synthetic calcium sensor.


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