Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires

Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in ne...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-02, Vol.109 (6), p.2114-2119
Main Authors: Miller, Evan W, Lin, John Y, Frady, E. Paxon, Steinbach, Paul A, Kristan, William B. Jr, Tsien, Roger Y
Format: Article
Language:English
Subjects:
Action potential
Action potentials
Action Potentials - physiology
Animals
Anions
Biological Sciences
Brain
Capacitance
Cell membranes
Dyes
Electric potential
Electron transfer
Electron Transport - radiation effects
Fluorescence
Fluorescent Dyes - chemistry
Fluorescent Dyes - metabolism
fluorophores
Ganglia
Ganglia, Invertebrate - physiology
HEK293 Cells
Hippocampus
Hirudinea
Humans
Hydrophobicity
image analysis
Imaging
Ion channels
Kinetics
Leeches - physiology
Light
Membrane potential
monitoring
nanowires
Neuromodulation
Neurons
Neurons - physiology
Neurons - radiation effects
Optics and Photonics - methods
Physical Sciences
Probes
Rats
Sensors
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Description
Summary:Fluorescence imaging is an attractive method for monitoring neuronal activity. A key challenge for optically monitoring voltage is development of sensors that can give large and fast responses to changes in transmembrane potential. We now present fluorescent sensors that detect voltage changes in neurons by modulation of photo-induced electron transfer (PeT) from an electron donor through a synthetic molecular wire to a fluorophore. These dyes give bigger responses to voltage than electrochromic dyes, yet have much faster kinetics and much less added capacitance than existing sensors based on hydrophobic anions or voltage-sensitive ion channels. These features enable single-trial detection of synaptic and action potentials in cultured hippocampal neurons and intact leech ganglia. Voltage-dependent PeT should be amenable to much further optimization, but the existing probes are already valuable indicators of neuronal activity.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1120694109