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Two-photon uncaging of γ-aminobutyric acid in intact brain tissue

Nature Chemical Biology volume 6, pages 255257 (2010) | Download Citation

Abstract

We have synthesized a photosensitive (or caged) 4-carboxymethoxy-5,7-dinitroindolinyl (CDNI) derivative of γ-aminobutyric acid (GABA). Two-photon excitation of CDNI-GABA produced rapid activation of GABAergic currents in neurons in brain slices with an axial resolution of approximately 2 μm and enabled high-resolution functional mapping of GABA-A receptors. Two-photon uncaging of GABA, the main inhibitory neurotransmitter, should allow detailed studies of receptor function and synaptic integration with subcellular precision.

  • Compound C14H17N3O6

    4-Methoxy-7-nitroindolinyl-L-glutamate

  • Compound C15H16N4O10

    4-Carboxymethoxy-5,7-dinitroindolinyl-L-glutamate

  • Compound C14H16N4O8

    1-[4-Aminobutanoyl]-5,7-dinitroindolin-4-yloxy)acetic acid

  • Compound C15H18O7

    Picrotoxin

  • Compound C12H14N2O6

    α-Carboxy-o-nitrobenzyl 4-aminobutanoate

  • Compound C14H17N3O6

    1-[4-Aminobutanoyl]-7-nitroindolin-4-yloxy)acetic acid

  • Compound C11H13NO3

    Methyl(indolin-4-yloxy)acetate

  • Compound C20H28N2O6

    Methyl {1-[4-(tert-butoxycarbonylamino)butanoyl]indolin-4-yloxy}acetate

  • Compound C19H26N2O6

    1-[4-(tert-Butoxycarbonylamino)butanoyl]indolin-4-yloxy}acetic acid

  • Compound C14H17N3O6

    1-[4-Aminobutanoyl]-5-nitroindolin-4-yloxy)acetic acid

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Acknowledgements

This work was supported by US National Institutes of Health grant GM53395 (to G.C.R.E.-D.), a Grant-in-Aid for Scientific Research on Priority Areas (Elucidation of neural network function in the brain, number 20021008, to M.M.), a Grant-in-Aid for Young Scientists (A) (number 19680020, to M.M.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and funding from Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (to M.M.).

Author information

Author notes

    • Masanori Matsuzaki
    •  & Graham C R Ellis-Davies

    These authors contributed equally to this work.

Affiliations

  1. Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

    • Masanori Matsuzaki
    • , Tatsuya Hayama
    •  & Haruo Kasai
  2. Center for NanoBio Integration, University of Tokyo, Tokyo, Japan.

    • Masanori Matsuzaki
    • , Tatsuya Hayama
    •  & Haruo Kasai
  3. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

    • Graham C R Ellis-Davies

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Contributions

G.C.R.E.-D. made and characterized the caged compounds. M.M. and T.H. performed biological experiments and analyzed the data. H.K. provided resources and support for the biological experiments. G.C.R.E.-D. and M.M. wrote the manuscript.

Competing interests

G.C.R.E.-D. has filed a patent on dinitroindolinyl caged compounds.

Corresponding authors

Correspondence to Masanori Matsuzaki or Graham C R Ellis-Davies.

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    Supplementary Methods, Supplementary Figures 1–3 and Supplementary Table 1

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DOI

https://doi.org/10.1038/nchembio.321

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