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Optical control of NMDA-receptors with a diffusible photoswitch

Research output: Contribution to journalJournal article

Published
  • Laura Laprell
  • Emilienne Repak
  • Vilius Franckevicius
  • Felix Hartrampf
  • Jan Terhag
  • M. Hollmann
  • Martin Sumser
  • Nelson Rebola
  • David Di Gregorio
  • Dirk Trauner
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Article number8076
<mark>Journal publication date</mark>27/08/2015
<mark>Journal</mark>Nature Communications
Volume6
Number of pages11
Publication statusPublished
Original languageEnglish

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.