Optical control of NMDA-receptors with a diffusible photoswitch

Laprell, Laura and Repak, Emilienne and Franckevicius, Vilius and Hartrampf, Felix and Terhag, Jan and Hollmann, M. and Sumser, Martin and Rebola, Nelson and Di Gregorio, David and Trauner, Dirk (2015) Optical control of NMDA-receptors with a diffusible photoswitch. Nature Communications, 6. ISSN 2041-1723

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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.

Item Type:
Journal Article
Journal or Publication Title:
Nature Communications
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/3100
Subjects:
ID Code:
76459
Deposited By:
Deposited On:
03 Nov 2015 19:38
Refereed?:
Yes
Published?:
Published
Last Modified:
24 Nov 2020 03:29