New Genetically Engineered Proteins Allow Scientists to Watch Nerve Cells Spark in Real Time

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For release: Thursday, April 4, 2013

Watching Nerve Sparks

Researchers used a microscope to watch electrical signals in a neuron expressing the ArcLight A242 voltage sensor (picture above). The colored lines represent fluorescence in circled areas and the bottom lines represent the neuron’s voltage. Fluorescence changed when the neuron underwent an action potential (left lines) or smaller signals (right lines). Courtesy of Dr. Vincent A. Pieribone lab, The John B. Pierce Laboratory and Yale University School of Medicine, New Haven, CT

Neurons send electric sparks from one end of the cell to another.  The action potential, a distinctive change in voltage, is a hallmark of electric signaling in neurons.  Usually researchers directly mo nitor these signals with cumbersome electrodes or toxic voltage-sensitive dyes, or indirectly with calcium detectors.  For decades, they tried developing voltage-sensitive fluorescent proteins, called fluorogenetic voltage sensors, as a less-invasive alternative.  In addition, these detectors could be used in specific types of neurons, including ones that are inaccessible with traditional methods.  Previous attempts did not produce proteins sensitive enough to watch action potentials and subtle voltage changes in real time.

Recently, a group of NINDS-funded researchers solved this problem.  The researchers genetically engineered two proteins, called ArcLight A242 and ElectricPk, and then expressed, or made, these proteins in neurons.  Experiments in which the researchers simultaneously watched neurons fluoresce with a microscope and recorded voltages with electrodes showed that fluorescence changed in parallel with voltage, indicating the proteins are sensitive enough to accurately detect a variety of sparks (see video).  The results, published in Neuron and in PLoS One, suggest that researchers may finally be able to use fluorogenetic voltage sensors to simultaneously watch thousands of neurons spark throughout the nervous system.

These and other sensors are being a developed by a group of NINDS-funded researchers who are part of the Fluorogenetic Voltage Sensors Consortium.  The consortium was partly funded with grants from the American Recovery and Reinvestment Act.

For more information go to: www.fluorogenetic-voltage-sensors.org/

References:

Jin et al., “Single Action Potentials and Subthreshold Electrical Events Imaged in Neurons with a Fluorescent Protein Voltage Probe.” Neuron, September 6, 2012, Vol. 75, pp. 779-785. DOI:10.1016/j.neuron.2012.06.040

www.ncbi.nlm.nih.gov/pubmed/22958819

Barnett et al., “A Fluorescent, Genetically-Encoded Voltage Probe Capable of Resolving Action Potentials.” PLOS ONE, September 2012, Vol. 7(9), pp. e43454. DOI:10.1371/journal.pone.0043454

www.ncbi.nlm.nih.gov/pubmed/22970127

Last Modified April 10, 2013