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

Fingerprint

optical control
glutamates
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Triazoles
aspartates
Photons
Protein Isoforms
Neuronal Plasticity
photons
plastic properties
deactivation
learning
Plasticity
delivery
azobenzene
Learning
Irradiation
disorders
analogs

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., ... Trauner, D. (2015). Optical control of NMDA receptors with a diffusible photoswitch. Nature Communications, 6, [8076]. https://doi.org/10.1038/ncomms9076

Optical control of NMDA receptors with a diffusible photoswitch. / Laprell, Laura; Repak, Emilienne; Franckevicius, Vilius; Hartrampf, Felix; Terhag, Jan; Hollmann, Michael; Sumser, Martin; Rebola, Nelson; DiGregorio, David A.; Trauner, Dirk.

In: Nature Communications, Vol. 6, 8076, 27.08.2015.

Research output: Contribution to journalArticle

Laprell, L, Repak, E, Franckevicius, V, Hartrampf, F, Terhag, J, Hollmann, M, Sumser, M, Rebola, N, DiGregorio, DA & Trauner, D 2015, 'Optical control of NMDA receptors with a diffusible photoswitch', Nature Communications, vol. 6, 8076. https://doi.org/10.1038/ncomms9076
Laprell L, Repak E, Franckevicius V, Hartrampf F, Terhag J, Hollmann M et al. Optical control of NMDA receptors with a diffusible photoswitch. Nature Communications. 2015 Aug 27;6. 8076. https://doi.org/10.1038/ncomms9076
Laprell, Laura ; Repak, Emilienne ; Franckevicius, Vilius ; Hartrampf, Felix ; Terhag, Jan ; Hollmann, Michael ; Sumser, Martin ; Rebola, Nelson ; DiGregorio, David A. ; Trauner, Dirk. / Optical control of NMDA receptors with a diffusible photoswitch. In: Nature Communications. 2015 ; Vol. 6.
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