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, Dirk Trauner

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number8076
JournalNature communications
Volume6
DOIs
StatePublished - Aug 27 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

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, [8076]. https://doi.org/10.1038/ncomms9076