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  • Florey Department of Neuroscience and Mental Health
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    Optical control of NMDA receptors with a diffusible photoswitch

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    Author
    Laprell, L; Repak, E; Franckevicius, V; Hartrampf, F; Terhag, J; Hollmann, M; Sumser, M; Rebola, N; DiGregorio, DA; Trauner, D
    Date
    2015-08-01
    Source Title
    Nature Communications
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Terhag, Jan
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Laprell, L., Repak, E., Franckevicius, V., Hartrampf, F., Terhag, J., Hollmann, M., Sumser, M., Rebola, N., DiGregorio, D. A. & Trauner, D. (2015). Optical control of NMDA receptors with a diffusible photoswitch. NATURE COMMUNICATIONS, 6 (1), https://doi.org/10.1038/ncomms9076.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/257543
    DOI
    10.1038/ncomms9076
    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 Ca(2+) 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.

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