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Optical control of NMDA receptors with a diffusible photoswitch

Author

Listed:
  • Laura Laprell

    (Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science)

  • Emilienne Repak

    (Institut Pasteur, Unit of Dynamic Neuronal Imaging
    CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur)

  • 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
    CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur)

  • David A. DiGregorio

    (Institut Pasteur, Unit of Dynamic Neuronal Imaging
    CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur)

  • Dirk Trauner

    (Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science)

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.

Suggested Citation

  • Laura Laprell & Emilienne Repak & Vilius Franckevicius & Felix Hartrampf & Jan Terhag & Michael Hollmann & Martin Sumser & Nelson Rebola & David A. DiGregorio & Dirk Trauner, 2015. "Optical control of NMDA receptors with a diffusible photoswitch," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9076
    DOI: 10.1038/ncomms9076
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