TY - JOUR
T1 - Optical control of NMDA receptors with a diffusible photoswitch
AU - Laprell, Laura
AU - Repak, Emilienne
AU - Franckevicius, Vilius
AU - Hartrampf, Felix
AU - Terhag, Jan
AU - Hollmann, Michael
AU - Sumser, Martin
AU - Rebola, Nelson
AU - DiGregorio, David A.
AU - Trauner, Dirk
PY - 2015/8/27
Y1 - 2015/8/27
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms9076
DO - 10.1038/ncomms9076
M3 - Article
C2 - 26311290
AN - SCOPUS:84940478401
SN - 2041-1723
VL - 6
JO - Nature communications
JF - Nature communications
M1 - 8076
ER -