Optical control of NMDA receptors with a diffusible photoswitch

Laura Laprell, Emilienne Repak, Vilius Franckevicius, Felix Hartrampf, Jan Terhag, Michael Hollmann, Martin Sumser, Nelson Rebola, David A. DiGregorio () and Dirk Trauner ()
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Laura Laprell: Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science
Emilienne Repak: Institut Pasteur, Unit of Dynamic Neuronal Imaging
Vilius Franckevicius: Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science
Felix Hartrampf: Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science
Jan Terhag: Ruhr-Universität-Bochum
Michael Hollmann: Ruhr-Universität-Bochum
Martin Sumser: Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science
Nelson Rebola: Institut Pasteur, Unit of Dynamic Neuronal Imaging
David A. DiGregorio: Institut Pasteur, Unit of Dynamic Neuronal Imaging
Dirk Trauner: Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable agonist. ATG is inactive in its dark-adapted trans-isoform, but can be converted into its active cis-isoform using one-photon (near UV) or two-photon (740 nm) excitation. Irradiation with violet light photo-inactivates ATG within milliseconds, allowing agonist removal on the timescale of NMDAR deactivation. ATG is compatible with Ca2+ imaging and can be used to optically mimic synaptic coincidence detection protocols. Thus, ATG can be used like traditional caged glutamate compounds, but with the added advantages of NMDAR specificity, low antagonism of GABAR-mediated currents, and precise temporal control of agonist delivery.

Date: 2015
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DOI: 10.1038/ncomms9076

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