title: Optical control of NMDA receptors with a diffusible photoswitch.
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.
authors: Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich 81377, Germany.
authors: Laura
authors: L
authors: Laprell
authors: Institut Pasteur, Unit of Dynamic Neuronal Imaging, 25 rue du Dr Roux, Paris Cedex 15 75724, France.|CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur, 25 rue du Dr Roux, Paris Cedex 15 75724, France.
authors: Emilienne
authors: E
authors: Repak
authors: Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich 81377, Germany.
authors: Vilius
authors: V
authors: Franckevicius
authors: Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich 81377, Germany.
authors: Felix
authors: F
authors: Hartrampf
authors: Ruhr-Universität-Bochum, Department of Biochemistry, Bochum 44780, Germany.
authors: Jan
authors: J
authors: Terhag
authors: Ruhr-Universität-Bochum, Department of Biochemistry, Bochum 44780, Germany.
authors: Michael
authors: M
authors: Hollmann
authors: Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich 81377, Germany.
authors: Martin
authors: M
authors: Sumser
authors: Institut Pasteur, Unit of Dynamic Neuronal Imaging, 25 rue du Dr Roux, Paris Cedex 15 75724, France.|CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur, 25 rue du Dr Roux, Paris Cedex 15 75724, France.
authors: Nelson
authors: N
authors: Rebola
authors: Institut Pasteur, Unit of Dynamic Neuronal Imaging, 25 rue du Dr Roux, Paris Cedex 15 75724, France.|CNRS UMR 3571, Genes, Synapses, and Cognition, Institut Pasteur, 25 rue du Dr Roux, Paris Cedex 15 75724, France.
authors: David A
authors: DA
authors: DiGregorio
authors: Department of Chemistry and Pharmacology, Ludwig-Maximilians-Universität, München, and Center for Integrated Protein Science, Munich 81377, Germany.
authors: Dirk
authors: D
authors: Trauner
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D018698:Glutamic Acid / Q000031:analogs & derivatives*; D006624:Hippocampus / Q000378:metabolism; D008027:Light; D051379:Mice; D009865:Oocytes; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D014982:Xenopus laevis
chemical_list: D018698:Glutamic Acid; D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor